tag:theconversation.com,2011:/fr/topics/antidepressants-1013/articlesAntidepressants – The Conversation2024-03-19T19:45:12Ztag:theconversation.com,2011:article/2235442024-03-19T19:45:12Z2024-03-19T19:45:12ZHalf of Australians in aged care have depression. Psychological therapy could help<figure><img src="https://images.theconversation.com/files/581494/original/file-20240313-16-lmeqav.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5991%2C3997&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/elderly-woman-sitting-on-wheelchair-looking-2033086775">sasirin pamai/Shutterstock</a></span></figcaption></figure><p>While many people maintain positive emotional wellbeing as they age, around half of older Australians living in residential aged care have <a href="https://research.sahmri.org.au/en/publications/the-prevalence-trends-and-determinants-of-mental-health-disorders">significant levels of depression</a>. Symptoms such as low mood, lack of interest or pleasure in life and difficulty sleeping are common. </p>
<p>Rates of depression in aged care appear to be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251748/">increasing</a>, and without adequate treatment, symptoms can be enduring and significantly impair older adults’ quality of life. </p>
<p>But only a minority of aged care residents with depression receive services specific to the condition. Less than 3% of Australian aged care residents access <a href="https://static1.squarespace.com/static/5b8c84fc4cde7abe6c3e7d7c/t/637af471f1a9621ed169fc24/1669002355850/Gov+mental+Health+infographic+FINAL_19-10-2022.pdf">Medicare-subsidised mental health services</a>, such as consultations with a psychologist or psychiatrist, each year. </p>
<figure class="align-center ">
<img alt="An infographic showing the percentage of Australian aged care residents with depression (53%)." src="https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=476&fit=crop&dpr=1 600w, https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=476&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=476&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=598&fit=crop&dpr=1 754w, https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=598&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/582461/original/file-20240318-16-8nfghk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=598&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Cochrane Australia</span></span>
</figcaption>
</figure>
<p>Instead, residents are typically prescribed a medication by their GP to manage their mental health, which they often take for several months or years. A <a href="https://www.jamda.com/article/S1525-8610(24)00082-3/abstract">recent study</a> found six in ten Australian aged care residents take antidepressants.</p>
<p>While antidepressant medications may help many people, we lack robust evidence on whether they work for <a href="https://www.jamda.com/article/S1525-8610(11)00306-9/abstract">aged care residents with depression</a>. Researchers <a href="https://academic.oup.com/biomedgerontology/article/77/5/1055/6425112">have described</a> “serious limitations of the current standard of care” in reference to the widespread use of antidepressants to treat frail older people with depression.</p>
<p>Given this, we wanted to find out whether psychological therapies can help manage depression in this group. These treatments address factors contributing to people’s distress and provide them with skills to manage their symptoms and improve their day-to-day lives. But to date researchers, care providers and policy makers haven’t had clear information about their effectiveness for treating depression among older people in residential aged care. </p>
<p>The good news is the <a href="https://www.cochranelibrary.com/web/cochrane/content?templateType=full&urlTitle=/cdsr/doi/10.1002/14651858.CD013059.pub2&doi=10.1002/14651858.CD013059.pub2&type=cdsr&contentLanguage=es">evidence we published today</a> suggests psychological therapies may be an effective approach for people living in aged care. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-are-so-many-australians-taking-antidepressants-221857">Why are so many Australians taking antidepressants?</a>
</strong>
</em>
</p>
<hr>
<h2>We reviewed the evidence</h2>
<p>Our research team searched for randomised controlled trials published over the past 40 years that were designed to test the effectiveness of psychological therapies for depression among aged care residents 65 and over. We identified 19 trials from seven countries, including Australia, involving a total of 873 aged care residents with significant symptoms of depression.</p>
<p>The studies tested several different kinds of psychological therapies, which we classified as cognitive behavioural therapy (CBT), behaviour therapy or reminiscence therapy. </p>
<p>CBT involves teaching practical skills to help people re-frame negative thoughts and beliefs, while behaviour therapy aims to modify behaviour patterns by encouraging people with depression to engage in pleasurable and rewarding activities. Reminiscence therapy supports older people to reflect on positive or shared memories, and helps them find meaning in their life history.</p>
<p>The therapies were delivered by a range of professionals, including psychologists, social workers, occupational therapists and trainee therapists. </p>
<figure class="align-center ">
<img alt="An infographic depicting what the researchers measured in the review." src="https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=486&fit=crop&dpr=1 600w, https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=486&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=486&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=611&fit=crop&dpr=1 754w, https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=611&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/582462/original/file-20240318-26-4oweov.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=611&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Cochrane Australia</span></span>
</figcaption>
</figure>
<p>In these studies, psychological therapies were compared to a control group where the older people did not receive psychological therapy. In most studies, this was “usual care” – the care typically provided to aged care residents, which may include access to antidepressants, scheduled activities and help with day-to-day tasks. </p>
<p>In some studies psychological therapy was compared to a situation where the older people received extra social contact, such as visits from a volunteer or joining in a discussion group.</p>
<h2>What we found</h2>
<p>Our results showed psychological therapies may be effective in reducing symptoms of depression for older people in residential aged care, compared with usual care, with effects lasting up to six months. While we didn’t see the same effect beyond six months, only two of the studies in our review followed people for this length of time, so the data was limited.</p>
<p>Our findings suggest these therapies may also improve quality of life and psychological wellbeing. </p>
<p>Psychological therapies mostly included between two and ten sessions, so the interventions were relatively brief. This is positive in terms of the potential feasibility of delivering psychological therapies at scale. The three different therapy types all appeared to be effective, compared to usual care. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/too-many-australians-living-in-nursing-homes-take-their-own-lives-92112">Too many Australians living in nursing homes take their own lives</a>
</strong>
</em>
</p>
<hr>
<p>However, we found psychological therapy may not be more effective than extra social contact in reducing symptoms of depression. Older people commonly feel bored, lonely and socially isolated in aged care. The activities on offer are often <a href="https://onlinelibrary.wiley.com/doi/10.1111/jocn.14978">inadequate</a> to meet their needs for stimulation and interest. So identifying ways to increase meaningful engagement day-to-day could improve the mental health and wellbeing of older people in aged care.</p>
<h2>Some limitations</h2>
<p>Many of the studies we found were of relatively poor quality, because of small sample sizes and potential risk of bias, for example. So we need more high-quality research to increase our confidence in the findings.</p>
<p>Many of the studies we reviewed were also old, and important gaps remain. For example, we are yet to understand the effectiveness of psychological therapies for people from diverse cultural or linguistic backgrounds. </p>
<p>Separately, we need better research to evaluate the effectiveness of antidepressants among aged care residents.</p>
<h2>What needs to happen now?</h2>
<p>Depression should not be considered a “normal” experience at this (or any other) stage of life, and those experiencing symptoms should have equal access to a range of effective treatments. The <a href="https://www.royalcommission.gov.au/system/files/2021-03/final-report-volume-2.pdf">royal commission into aged care</a> highlighted that Australians living in aged care don’t receive enough mental health support and called for this issue to be addressed.</p>
<p>While there have been some efforts to provide <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajag.12895">psychological services</a> in residential aged care, the unmet need remains very high, and much more must be done. </p>
<p>The focus now needs to shift to how to implement psychological therapies in aged care, by increasing the competencies of the aged care workforce, training the next generation of psychologists to work in this setting, and funding these programs in a cost-effective way. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-our-residential-aged-care-system-doesnt-care-about-older-peoples-emotional-needs-103336">How our residential aged-care system doesn't care about older people's emotional needs</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/223544/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tanya Davison currently receives research funding from the Medical Research Future Fund (MRFF), Australian Research Council (ARC), and Aged Care Research and Industry Innovation Australia (ARIIA). She is employed as Director of Research Discovery at Silverchain (an Australian in-home care provider) and is a committee member of the Australian Psychological Society (APS) Psychology and Ageing Interest Group. </span></em></p><p class="fine-print"><em><span>Sunil Bhar currently receives research funding from the Medical Research Future Fund (MRFF), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), Aged Care Research and Industry Innovation Australia (ARIIA), The Ian Potter Foundation (IPF) and Arcare Family Foundation (AFF). He is the Director of the Swinburne Wellbeing Clinic for Older Adults (a free counselling service for aged care residents) and is employed as Professor of Clinical Psychology at Swinburne University. He is a committee member of the Australian Psychological Society (APS) Psychology and Ageing Interest Group.</span></em></p>A new review looks at whether psychological therapies, such as cognitive behavioural therapy, are an effective way to treat older people in aged care with symptoms of depression.Tanya Davison, Adjunct professor, Health & Ageing Research Group, Swinburne University of TechnologySunil Bhar, Professor of Clinical Psychology, Swinburne University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2234412024-02-15T02:57:24Z2024-02-15T02:57:24ZRunning or yoga can help beat depression, research shows – even if exercise is the last thing you feel like<figure><img src="https://images.theconversation.com/files/575486/original/file-20240213-16-fi0ivc.jpg?ixlib=rb-1.1.0&rect=0%2C1%2C1000%2C664&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/exercise-healthy-concept-fat-woman-feeling-1095177362">SKT Studio/Shutterstock</a></span></figcaption></figure><p>At least <a href="https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.665019/full">one in ten people</a> have depression at some point in their lives, with some estimates <a href="https://www.sciencedirect.com/science/article/pii/S0749379720301793">closer to one in four</a>. It’s one of the worst things for someone’s wellbeing – worse than <a href="https://www.happinessresearchinstitute.com/_files/ugd/928487_4a99b6e23f014f85b38495b7ab1ac24b.pdf">debt, divorce or diabetes</a>.</p>
<p><a href="https://theconversation.com/why-are-so-many-australians-taking-antidepressants-221857">One in seven</a> Australians take antidepressants. Psychologists are in <a href="https://theconversation.com/we-cant-solve-australias-mental-health-emergency-if-we-dont-train-enough-psychologists-here-are-5-fixes-190135">high demand</a>. Still, only <a href="http://dx.doi.org/10.1371/journal.pmed.1003901">half</a> of people with depression in high-income countries get treatment. </p>
<p>Our <a href="https://www.bmj.com/content/384/bmj-2023-075847">new research</a> shows that exercise should be considered alongside therapy and antidepressants. It can be just as impactful in treating depression as therapy, but it matters what type of exercise you do and how you do it.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-are-so-many-australians-taking-antidepressants-221857">Why are so many Australians taking antidepressants?</a>
</strong>
</em>
</p>
<hr>
<h2>Walk, run, lift, or dance away depression</h2>
<p>We found 218 randomised trials on exercise for depression, with 14,170 participants. We analysed them using a method called a network meta-analysis. This allowed us to see how different types of exercise compared, instead of lumping all types together. </p>
<p>We found walking, running, strength training, yoga and mixed aerobic exercise were about as effective as <a href="https://theconversation.com/explainer-what-is-cognitive-behaviour-therapy-37351">cognitive behaviour therapy</a> – one of the <a href="https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00004/full">gold-standard treatments</a> for depression. The effects of dancing were also powerful. However, this came from analysing just five studies, mostly involving young women. Other exercise types had more evidence to back them.</p>
<p>Walking, running, strength training, yoga and mixed aerobic exercise seemed more effective than antidepressant medication alone, and were about as effective as exercise alongside antidepressants.</p>
<p>But of these exercises, people were most likely to stick with strength training and yoga.</p>
<p><iframe id="cZaWb" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/cZaWb/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Antidepressants certainly help <a href="https://www.thelancet.com/article/S0140-6736(17)32802-7/fulltext">some people</a>. And of course, anyone getting treatment for depression should talk to their doctor <a href="https://australia.cochrane.org/news/new-cochrane-review-explores-latest-evidence-approaches-stopping-long-term-antidepressants">before changing</a> what they are doing. </p>
<p>Still, our evidence shows that if you have depression, you should get a psychologist <em>and</em> an exercise plan, whether or not you’re taking antidepressants.</p>
<h2>Join a program and go hard (with support)</h2>
<p>Before we analysed the data, we thought people with depression might need to “ease into it” with generic advice, <a href="https://www.who.int/initiatives/behealthy/physical-activity">such as</a> “some physical activity is better than doing none.”</p>
<p>But we found it was far better to have a clear program that aimed to push you, at least a little. Programs with clear structure worked better, compared with those that gave people lots of freedom. Exercising by yourself might also make it hard to set the bar at the right level, given low self-esteem is a symptom of depression.</p>
<p>We also found it didn’t matter how much people exercised, in terms of sessions or minutes a week. It also didn’t really matter how long the exercise program lasted. What mattered was the intensity of the exercise: the higher the intensity, the better the results.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1618986138118803457"}"></div></p>
<h2>Yes, it’s hard to keep motivated</h2>
<p>We should exercise caution in interpreting the findings. Unlike drug trials, participants in exercise trials know which “treatment” they’ve been randomised to receive, so this may skew the results.</p>
<p>Many people with depression have physical, psychological or social barriers to participating in formal exercise programs. And getting support to exercise isn’t free. </p>
<p>We also still don’t know the best way to stay motivated to exercise, which can be even harder if you have depression.</p>
<p>Our study tried to find out whether things like setting exercise goals helped, but we couldn’t get a clear result.</p>
<p>Other reviews found it’s important to have a <a href="https://pubmed.ncbi.nlm.nih.gov/31923898/">clear action plan</a> (for example, putting exercise in your calendar) and to <a href="https://pubmed.ncbi.nlm.nih.gov/19916637/">track your progress</a> (for example, using an app or smartwatch). But predicting which of these interventions work is notoriously difficult. </p>
<p>A <a href="https://www.nature.com/articles/s41586-021-04128-4">2021 mega-study</a> of more than 60,000 gym-goers <a href="https://www.nature.com/articles/s41586-021-04128-4/figures/1">found</a> experts struggled to predict which strategies might get people into the gym more often. Even making workouts fun didn’t seem to motivate people. However, listening to audiobooks while exercising helped a lot, which no experts predicted.</p>
<p>Still, we can be confident that people benefit from personalised support and accountability. The support helps overcome the hurdles they’re sure to hit. The accountability keeps people going even when their brains are telling them to avoid it. </p>
<p>So, when starting out, it seems wise to avoid going it alone. Instead:</p>
<ul>
<li><p>join a fitness group or yoga studio</p></li>
<li><p>get a trainer or an exercise physiologist</p></li>
<li><p>ask a friend or family member to go for a walk with you. </p></li>
</ul>
<p>Taking a few steps towards getting that support makes it more likely you’ll keep exercising.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/exercise-is-even-more-effective-than-counselling-or-medication-for-depression-but-how-much-do-you-need-200717">Exercise is even more effective than counselling or medication for depression. But how much do you need?</a>
</strong>
</em>
</p>
<hr>
<h2>Let’s make this official</h2>
<p>Some countries see exercise as a backup plan for treating depression. For example, the American Psychological Association only <a href="https://www.apa.org/depression-guideline/">conditionally recommends</a> exercise as a “complementary and alternative treatment” when “psychotherapy or pharmacotherapy is either ineffective or unacceptable”.</p>
<p>Based on our research, this recommendation is withholding a potent treatment from many people who need it.</p>
<p>In contrast, The Royal Australian and New Zealand College of Psychiatrists <a href="https://www.ranzcp.org/getmedia/a4678cf4-91f5-4746-99d4-03dc7379ae51/mood-disorders-clinical-practice-guideline-2020.pdf">recommends</a> vigorous aerobic activity at least two to three times a week for all people with depression.</p>
<p>Given how common depression is, and the number failing to receive care, other countries should follow suit and recommend exercise alongside front-line treatments for depression.</p>
<p><em>I would like to acknowledge my colleagues Taren Sanders, Chris Lonsdale and the rest of the coauthors of the paper on which this article is based.</em></p>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14.</em></p><img src="https://counter.theconversation.com/content/223441/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Noetel receives funding from the Australian Research Council, the Medical Research Future Fund, Sport Australia, and the National Health and Medical Research Council. He is a director of Effective Altruism Australia.</span></em></p>Our new study shows you may be able to walk, run, lift or dance away depression. And the more intense your exercise program, the better.Michael Noetel, Senior Lecturer in Psychology, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2218572024-02-08T19:17:54Z2024-02-08T19:17:54ZWhy are so many Australians taking antidepressants?<figure><img src="https://images.theconversation.com/files/573713/original/file-20240206-26-8fjigm.jpg?ixlib=rb-1.1.0&rect=49%2C16%2C5406%2C3620&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-woman-taking-tablet-glass-water-1498026977">Daisy Daisy/Shutterstock</a></span></figcaption></figure><p>Around <a href="https://australia.cochrane.org/news/new-cochrane-review-explores-latest-evidence-approaches-stopping-long-term-antidepressants">one in seven Australians</a> take antidepressants; more than <a href="https://www.aihw.gov.au/mental-health/topic-areas/mental-health-prescriptions">3.5 million</a> of us had them dispensed in 2021–22. This is <a href="https://www.mja.com.au/journal/2016/204/9/unfulfilled-promise-antidepressant-medications#:%7E:text=Summary,is%20lower%20than%20previously%20thought.">one of the highest</a> antidepressant prescribing rates in the world. </p>
<p>Guidelines mostly recommend antidepressants for <a href="https://www.nice.org.uk/guidance/ng222">more severe depression</a> and <a href="https://www.nice.org.uk/guidance/cg113/resources/generalised-anxiety-disorder-and-panic-disorder-in-adults-management-pdf-35109387756997">anxiety</a> but not as first-line treatment for less severe depression. Less commonly, antidepressants may be <a href="https://www.ncbi.nlm.nih.gov/books/NBK538182/">prescribed for</a> conditions such as chronic pain and migraine.</p>
<p>Yet prescription rates continue to increase. Between 2013 and 2021, the antidepressant prescription rate in Australia <a href="https://www.publish.csiro.au/PY/pdf/PY23168">steadily increased</a> by 4.5% per year. So why are so many Australians taking antidepressants and why are prescriptions rising? </p>
<p>The evidence suggests they’re over-prescribed. So how did we get here?</p>
<h2>Enter the antidepressant ‘blockbusters’</h2>
<p>In the 1990s, pharmaceutical companies <a href="https://www.nature.com/articles/d41573-022-00213-z">heavily promoted</a> new selective serotonin reuptake inhibitor (SSRI) antidepressants, including Prozac (fluoxetine), Zoloft (sertraline) and Lexapro (escitalopram). </p>
<p>These drugs were thought to be less dangerous in overdoses and seemed to have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155/">fewer side effects</a> than the tricyclic antidepressants they replaced. </p>
<p>Pharmaceutical companies marketed SSRIs energetically and often exaggerated their benefits, including by paying “key opinion leaders” – <a href="https://www.bmj.com/content/336/7658/1402">high-status clinicians</a> to promote them. This prompted <a href="https://www.mja.com.au/journal/2004/181/7/making-new-choices-about-antidepressants-australia-long-view-1975-2002">substantial growth</a> in the market.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-need-new-rules-for-defining-who-is-sick-step-1-remove-vested-interests-114621">We need new rules for defining who is sick. Step 1: remove vested interests</a>
</strong>
</em>
</p>
<hr>
<p>SSRIs earned billions of dollars for their manufacturers when on patent. While now relatively cheap, they still prove <a href="https://www.prnewswire.com/news-releases/antidepressant-drugs-market-to-reach-15-98-bn-by-2023-globally-at-2-1-cagr-says-allied-market-research-873540700.html">lucrative</a> because of high prescribing levels. </p>
<h2>Why are antidepressants prescribed?</h2>
<p>The majority (85%) of antidepressants are prescribed in <a href="https://www.aihw.gov.au/mental-health/topic-areas/mental-health-prescriptions">general practice</a>. Some are prescribed for more severe depression and anxiety. But contrary to clinical guidelines, GPs also <a href="https://www1.racgp.org.au/ajgp/2021/december/antidepressant-prescribing-in-general-practice">prescribe</a> them as a first-line treatment for less severe depression.</p>
<p>GPs also prescribe antidepressants to patients experiencing distress but who don’t have a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504011/#:%7E:text=Among%20antidepressant%20users%2C%2069%25%20never,current%20physical%20problems%20(e.g.%2C%20loss">psychiatric diagnosis</a>. A friend dealing with her husband’s terminal illness, for example, was encouraged to take antidepressants by her long-term GP, even though her caring capacity wasn’t impaired. Another, who cried when informed she had breast cancer, was immediately offered a prescription for antidepressants. </p>
<figure class="align-center ">
<img alt="GP writes a script" src="https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573716/original/file-20240206-30-a4nh4l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Sometimes patients who don’t have a psychiatric diagnosis receive antidepressants.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-patient-consulting-room-gp-surgery-2367985555">Stephen Barnes/Shutterstock</a></span>
</figcaption>
</figure>
<p>There are several reasons why someone may take antidepressants when they’re not needed. A busy GP might be looking for a convenient solution to a complex and sometimes intractable problem. Other times, patients request a prescription. They may be encouraged by an <a href="https://www.theaustralian.com.au/inquirer/seratonin-theory-of-depression-under-attack-amid-to-push-to-deprescribe-antidepressants/news-story/f74ca1a6018110e3d680b8d5ce01bc2c">acquaintance’s good experience</a> or looking for other ways to <a href="https://www.penguinrandomhouse.com/books/321259/listening-to-prozac-by-peter-d-kramer/">improve their mental health</a>. </p>
<p>Most patients believe antidepressants restore a chemical imbalance that underpins depression. This is <a href="https://www.nature.com/articles/s41380-022-01661-0">not true</a>. Antidepressants are emotional (and sexual) <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155/">numbing agents</a> – sometimes sedating, sometimes energising. Those effects suit some people, for example, if their emotions are too raw or they lack energy. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-chemical-imbalance-theory-of-depression-is-dead-but-that-doesnt-mean-antidepressants-dont-work-187769">The chemical imbalance theory of depression is dead, but that doesn't mean antidepressants don't work</a>
</strong>
</em>
</p>
<hr>
<p>For others, they come with <a href="https://www.healthdirect.gov.au/antidepressants">troubling side effects</a> such as insomnia, restlessness, nausea, weight gain. Around half of users have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007725/">impaired sexual function</a> and for some, this <a href="https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/s12991-023-00447-0">sexual dysfunction persists</a> after stopping antidepressants. </p>
<h2>How long do people take antidepressants?</h2>
<p>Most experts and <a href="https://www.nice.org.uk/guidance/ng222">guidelines</a> recommend specific prescribing regimes of antidepressants, varying from months to two years. </p>
<p>However, most antidepressants are consumed by two categories of people. Around half of patients who start antidepressants don’t like them and <a href="https://bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-9-38#:%7E:text=Medication%20possession%20rates&text=Although%20the%20mean%20MPR%20of,group%20difference%20(Table%203).">stop within weeks</a>. Of those who do take them for months, many continue to use them indefinitely, often for many years. <a href="https://www1.racgp.org.au/ajgp/2021/december/antidepressant-prescribing-in-general-practice">Long-term use</a> (beyond 12 months) is driving much of the increase in antidepressant prescribing.</p>
<p>Some people try to stop taking antidepressants but are prevented from doing so by <a href="https://www.sciencedirect.com/science/article/abs/pii/S221503661930032X">withdrawal symptoms</a>. Withdrawal symptoms – including “<a href="https://pubmed.ncbi.nlm.nih.gov/35144325/">brain zaps</a>”, dizziness, restlessness, vertigo and vomiting – can cause significant distress, impaired work function and relationship breakdown. </p>
<p>Across 14 studies that examined antidepressant withdrawal, around 50% of users <a href="https://www.sciencedirect.com/science/article/abs/pii/S221503661930032X">experienced withdrawal symptoms</a> when coming off antidepressants, which can be mistaken for recurrence of the initial problem. We are conducting a <a href="https://adelaideuniwide.qualtrics.com/jfe/form/SV_3QqWrY5TBNUP1YO">survey</a> to better understand the experience in Australia of withdrawing from antidepressants.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1495843401744347136"}"></div></p>
<p>Antidepressants should not be stopped abruptly but gradually tapered off, with smaller and smaller doses. The recent release in Australia of the <a href="https://www.wiley.com/en-au/The+Maudsley+Deprescribing+Guidelines%3A+Antidepressants%2C+Benzodiazepines%2C+Gabapentinoids+and+Z+drugs-p-9781119823025">Maudsley Deprescribing Guidelines</a> provides guidance for the complex regimes required for the tapering of antidepressants.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/antidepressants-can-cause-withdrawal-symptoms-heres-what-you-need-to-know-208224">Antidepressants can cause withdrawal symptoms – here’s what you need to know</a>
</strong>
</em>
</p>
<hr>
<h2>We need to adjust how we view mental distress</h2>
<p>Overprescribing antidepressants is a symptom of our lack of attention to the <a href="https://onlinelibrary.wiley.com/doi/10.1002/wps.21160">social determinants of mental health</a>. It’s depressing to be poor (especially when your neighbours seem rich), unemployed or in an awful workplace, inadequately housed or fearful of family violence. It’s wrong to locate the problem in the individual when it belongs to society.</p>
<p>Overprescribing is also symptomatic of medicalisation of distress. Most diagnoses of depression and anxiety are <a href="https://karger.com/psp/article-pdf/37/6/259/3489408/000081981.pdf">descriptions masquerading as explanations</a>. For each distressed person who fits the pattern of anxiety or depression, the meaning of their presentation is different. There may be a medical explanation, but most often meaning may be found in the person’s struggle with difficult feelings, their relationships and other life circumstances such as terrible disappointments or grief. </p>
<p>GPs’ overprescribing reflects the pressures they experience from workload, unrealistic expectations of their capacity and misinformation from pharmaceutical companies and key opinion leaders. They need better support, resources and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822978/">evidence</a> about the limited <a href="https://www.thelancet.com/article/S0140-6736(17)32802-7/fulltext">benefits</a> of antidepressants. </p>
<p>GPs also need to ensure they discuss with their patients the potential adverse effects of antidepressants, and when and how to safely stop them. </p>
<p>But the fundamental problem is social and can only be properly addressed by meaningfully addressing inequality and changing community attitudes to distress.</p><img src="https://counter.theconversation.com/content/221857/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jon Jureidini receives research funding from MMRF. He is affiliated with Critical Psychiatry Network Australasia.</span></em></p>Australia has among the highest antidepressant prescribing rates in the world.Jon Jureidini, Research Leader, Critical and Ethical Mental Health research group, Robinson Research Institute, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2228782024-02-07T09:54:48Z2024-02-07T09:54:48ZWomen take more antidepressants after divorce than men but that doesn’t mean they’re more depressed<figure><img src="https://images.theconversation.com/files/573951/original/file-20240207-18-751n5r.jpg?ixlib=rb-1.1.0&rect=48%2C164%2C4009%2C2536&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/man-and-woman-sitting-on-bench-facing-sea-78hTqvjYMS4">Matt Bennett/Unsplash</a></span></figcaption></figure><p>Research out today from Finland <a href="https://jech.bmj.com/lookup/doi/10.1136/jech-2023-221529">suggests</a> women may find it harder to adjust to later-life divorce and break-ups than men.</p>
<p>The <a href="https://jech.bmj.com/lookup/doi/10.1136/jech-2023-221529">study</a> used population data from 229,000 Finns aged 50 to 70 who had undergone divorce, relationship break-up or bereavement and tracked their use of antidepressants before and after their relationship ended. </p>
<p>They found antidepressant use increased in the four years leading to the relationship dissolution in both genders, with women experiencing a more significant increase.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1755011769029066857"}"></div></p>
<p>But it’s too simplistic to say women experience poorer mental health or tend to be less happy after divorce than men. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-breakups-are-so-hard-and-how-to-cope-with-them-96339">Why breakups are so hard and how to cope with them</a>
</strong>
</em>
</p>
<hr>
<h2>Remind me, how common is divorce?</h2>
<p>Just under <a href="https://www.abs.gov.au/statistics/people/people-and-communities/marriages-and-divorces-australia/latest-release">50,000</a> divorces are granted each year in Australia. This has slowly <a href="https://aifs.gov.au/research/facts-and-figures/divorces-australia">declined</a> since the 1990s. </p>
<p>More couple are <a href="https://aifs.gov.au/research/research-reports/families-then-now-couple-relationships">choosing to co-habitate</a>, instead of marry, and the majority of couples live together prior to marriage. <a href="https://psycnet.apa.org/record/2011-13994-007">Divorce statistics</a> don’t include separations of cohabiting couples, even though they are more likely than married couples to separate.</p>
<p>Those who divorce are doing so <a href="https://aifs.gov.au/research/research-reports/families-then-now-couple-relationships">later in life</a>, often after their children grow up. The <a href="https://www.abs.gov.au/statistics/people/people-and-communities/marriages-and-divorces-australia/latest-release">median age</a> of divorce increased from 45.9 in 2021 to 46.7 in 2022 for men and from 43.0 to 43.7 for women. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=265&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=265&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=265&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=333&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=333&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573920/original/file-20240206-16-t4kyzp.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=333&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Median age of men and women at divorce, 1971–2020.</span>
<span class="attribution"><a class="source" href="https://aifs.gov.au/research/facts-and-figures/divorces-australia">ABS, (various years), Marriages and Divorces Australia; ABS, (various years), Divorces Australia</a></span>
</figcaption>
</figure>
<p>The trend of late divorces also reflects people deciding to marry later in life. The median duration from marriage to divorce in 2022 was around <a href="https://www.abs.gov.au/statistics/people/people-and-communities/marriages-and-divorces-australia/latest-release">12.8 years</a> and has remained <a href="https://aifs.gov.au/research/facts-and-figures/divorces-australia">fairly constant</a> over the past decade. </p>
<h2>Why do couples get divorced?</h2>
<p>Changes in <a href="https://www.apa.org/monitor/2023/11/navigating-late-in-life-divorce">social attitudes towards marriage and relationships</a> mean divorce is now more accepted. People are opting not to be in unhappy marriages, even if there are children involved. </p>
<p>Instead, they’re turning the focus on marriage quality. This is particularly true for women who have established a career and are financially autonomous.</p>
<p>Similarly, my <a href="https://www.tandfonline.com/doi/full/10.1080/15332691.2020.1795039">research</a> shows it’s particularly important for people to feel their relationship expectations can be fulfilled long term. In addition to relationship quality, participants reported needing trust, open communication, safety and acceptance from their partners. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-last-nights-fight-affects-the-way-couples-divide-housework-92582">How last night's fight affects the way couples divide housework</a>
</strong>
</em>
</p>
<hr>
<p>“<a href="https://pubmed.ncbi.nlm.nih.gov/32450471/">Grey divorce</a>” (divorce at age 50 and older) is becoming increasingly common in Western countries, particularly among high-income populations. While factors such as an empty nest, retirement, or poor health are commonly cited predictors of later-in-life divorce, <a href="https://academic.oup.com/psychsocgerontology/article/73/6/1022/2698907">research</a> shows older couples divorce for the same reasons as younger couples. </p>
<h2>What did the new study find?</h2>
<p>The study tracked antidepressant use in Finns aged 50 to 70 for four years before their relationship breakdown and four years after.</p>
<p>They <a href="https://jech.bmj.com/lookup/doi/10.1136/jech-2023-221529">found</a> antidepressant use increased in the four years leading to the relationship break-up in both genders. The proportion of women taking antidepressants in the lead up to divorce increased by 7%, compared with 5% for men. For de facto separation antidepressant use increased by 6% for women and 3.2% for men.</p>
<p>Within a year of the break-up, antidepressant use fell back to the level it was 12 months before the break-up. It subsequently remained at that level among the men. </p>
<p>But it was a different story for women. Their use tailed off only slightly immediately after the relationship breakdown but increased again from the first year onwards.</p>
<figure class="align-center ">
<img alt="Woman sits at the beach" src="https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573943/original/file-20240207-20-tqec32.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Women’s antidepressant use increased again.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-sitting-on-seashore-jeEedhJXoR0">sk/Unsplash</a></span>
</figcaption>
</figure>
<p>The researchers also looked at antidepressant use after re-partnering. There was a decline in the use of antidepressants for men and women after starting a new relationship. But this decline was short-lived for women. </p>
<h2>But there’s more to the story</h2>
<p>Although this data alone suggest women may find it harder to adjust to later-life divorce and break-ups than men, it’s important to note some nuances in the interpretation of this data. </p>
<p>For instance, data suggesting women experience depression more often than men is generally based on the rate of diagnoses and antidepressant use, which does not account for undiagnosed and unmedicated people. </p>
<p>Women are generally more likely to access medical services and thus receive treatment. This is also the case in <a href="https://www.abs.gov.au/statistics/health/mental-health/national-study-mental-health-and-wellbeing/latest-release">Australia</a>, where in 2020–2022, 21.6% of women saw a health professional for their mental health, compared with only 12.9% of men.</p>
<h2>Why women might struggle more after separating</h2>
<p>Nevertheless, relationship dissolution can have a significant impact on people’s mental health. This is particularly the case for <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1741-3737.2006.00322.x">women with young children</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/28535241/">older women</a>.</p>
<p>So what factors might explain why women might experience greater difficulties after divorce later in life?</p>
<p><a href="https://academic.oup.com/psychsocgerontology/article/76/10/2073/5903434">Research</a> investigating the financial consequences of grey divorce in men and women showed women experienced a 45% decline in their standard of living (measured by an income-to-needs ratio), whereas men’s dropped by just 21%. These declines persisted over time for men, and only reversed for women following re-partnering. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/womens-probability-of-being-in-poverty-more-than-doubles-after-separation-181345">Women’s probability of being in poverty more than doubles after separation</a>
</strong>
</em>
</p>
<hr>
<p>Another <a href="https://scholarship.libraries.rutgers.edu/esploro/outputs/acceptedManuscript/991031549993104646/filesAndLinks?index=0">qualitative study</a> investigating the lived experiences of heterosexual couples post-grey divorce identified financial worries as a common theme between female participants. </p>
<p>A female research participant (age 68) said: </p>
<blockquote>
<p>[I am most worried about] the money, [and] what I’m going to do when the little bit of money I have runs out […] I have just enough money to live. And, that’s it, [and if] anything happens I’m up a creek. And Medicare is incredibly expensive […] My biggest expense is medicine.</p>
</blockquote>
<p>Another factor was loneliness. One male research participant (age 54) described he preferred living with his ex-wife, despite not getting along with her, than being by himself:</p>
<blockquote>
<p>It was still [good] knowing that [the] person was there, and now that’s gone.</p>
</blockquote>
<p>Other <a href="https://www.apa.org/monitor/2023/11/navigating-late-in-life-divorce">major complications of later-life divorce</a> are possible issues with inheritance rights and next-of-kin relationships for medical decision-making.</p>
<h2>Separation can be positive</h2>
<p>For some people, divorce or separation <a href="https://scholarship.libraries.rutgers.edu/esploro/outputs/acceptedManuscript/991031549993104646/filesAndLinks?index=0">can lead</a> to increased happiness and feeling more independent. </p>
<p>And the mental health impact and emotional distress of a relationship dissolution is something that can be counterattacked with resilience. Resilience to dramatic events built from life experience means <a href="https://psycnet.apa.org/doiLanding?doi=10.1037%2Fa0021232">older adults often do respond better to emotional distress</a> and might be able to <a href="https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpag0000761">adjust better to divorce</a> than their younger counterparts.</p><img src="https://counter.theconversation.com/content/222878/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Raquel Peel does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A Finnish study found antidepressant use increased among men and women in the four years leading to the relationship ending – but there was a larger increase among women.Raquel Peel, Adjunct Senior Lecturer, University of Southern Queensland and Senior Lecturer, RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2180452023-12-17T19:17:20Z2023-12-17T19:17:20ZIs it OK to take antidepressants while pregnant?<figure><img src="https://images.theconversation.com/files/564779/original/file-20231211-15-ucu6di.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3834%2C2160&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sad-pregnant-woman-holding-belly-sitting-1497946568">Motortion Films/Shutterstock</a></span></figcaption></figure><p>Mental health conditions including <a href="https://aps.onlinelibrary.wiley.com/doi/abs/10.1111/cp.12058">anxiety</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/34036464/">depression</a> are among the most common disorders affecting women <a href="https://pubmed.ncbi.nlm.nih.gov/25455248/">during pregnancy and after birth</a>. </p>
<p>Evidence shows <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879174/">mental health conditions</a> in pregnancy increase the risk of complications for the mother and baby.</p>
<p>However, there is <a href="https://www.smh.com.au/national/new-guidelines-aim-to-lift-stigma-around-antidepressants-during-pregnancy-20231109-p5eivo.html">some stigma</a> around taking antidepressants while pregnant or breastfeeding. So how should women decide whether or not to take antidepressants during these periods?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/antidepressants-and-pregnancy-study-didnt-find-they-actually-cause-autism-81271">Antidepressants and pregnancy: study didn't find they actually cause autism</a>
</strong>
</em>
</p>
<hr>
<h2>Mental health in pregnancy and after birth</h2>
<p>Untreated <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879174/">anxiety and depression</a> in pregnancy have been linked to an increased risk of stillbirth, premature birth, low birth weight and low APGAR scores (a test done at birth to check the baby’s health in various domains).</p>
<p>In addition, anxiety or depression during pregnancy may lead to increased maternal weight gain, substance use or smoking. These lifestyle factors can also <a href="https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-023-06090-7#">lead to complications</a> for the baby. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/30196868/">Anxiety and depression</a> during and <a href="https://pubmed.ncbi.nlm.nih.gov/27993226/">after pregnancy</a> can affect bonding between mother and baby, and hinder the child’s behavioural and emotional development.</p>
<p>Meanwhile, complications in the pregnancy may worsen mental health symptoms for the mother.</p>
<figure class="align-center ">
<img alt="A pregnant woman looks out a window." src="https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564782/original/file-20231211-23-wy06kc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Women may be reluctant to take medications while pregnant.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/love-joy-mother-1007992423">Tapao/Shutterstock</a></span>
</figcaption>
</figure>
<p>Not coping during pregnancy and especially after giving birth is demoralising and puts women at risk of self-harm. Suicide is a <a href="https://www.aihw.gov.au/reports/mothers-babies/maternal-deaths-australia#cause">leading cause</a> of maternal death in Australia in the <a href="https://clinicalexcellence.qld.gov.au/sites/default/files/docs/safety-and-quality/qmpqc-report-2021.pdf">year after giving birth</a>. </p>
<h2>Treatment options</h2>
<p>Depending on the severity of symptoms, treatment options for women during and after pregnancy range from social and emotional support (for example, support groups) to psychological interventions (such as cognitive behavioural therapy) to medical treatments (for example, antidepressants).</p>
<p>Understandably, many women <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013560.pub2/full">are reluctant</a> to take medications during pregnancy and while breastfeeding due to concerns the drugs may cross over to the baby and cause complications. Historical instances such as the use of thalidomide for morning sickness, which resulted in severe structural abnormalities in thousands of children, naturally make pregnant women worried.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/thalidomide-survivors-are-receiving-an-apology-for-the-pharmaceutical-disaster-that-changed-pregnancy-medicine-218691">Thalidomide survivors are receiving an apology for the pharmaceutical disaster that changed pregnancy medicine</a>
</strong>
</em>
</p>
<hr>
<p>Robust evidence about medication use in pregnancy is lacking. This may be due to ethical limitations around trialling medications in pregnant women. The limited data available, mainly from observational studies on selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096863/">most commonly prescribed</a> antidepressants during pregnancy, has mixed results. </p>
<p>While some studies have reported no noticeable increase in the risk of <a href="https://www.psychiatrist.com/jcp/antidepressant-exposure-during-pregnancy-congenital/">congenital malformations</a>, evidence has shown a marginal rise in abnormalities such as <a href="https://www.nice.org.uk/guidance/cg192">heart defects</a> (an extra two cases per 1,000 babies with SSRIs). </p>
<h2>Collaborative decisions</h2>
<p>There is a delicate balance to strike between treating the mother and preventing harm to the baby. To make well-informed decisions, an open discussion between the patient and specialised mental health care providers on the benefits and risks of starting or continuing antidepressants is essential. </p>
<p>Given the mother’s poor mental health increases the risk of adverse outcomes for the baby, it may well be that taking antidepressants is the best way to protect the baby.</p>
<p>For women already taking antidepressants, it’s not usually necessary to stop using them during pregnancy. Sudden cessation of antidepressants increases the risk <a href="https://pubmed.ncbi.nlm.nih.gov/16449615/">of relapse</a>.</p>
<p>Continuing breastfeeding on antidepressants is likely the best decision because of the low <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013560.pub2/full">levels of drugs</a> infants are exposed to in breast milk, the advantages of breastfeeding for the baby, and the risks of not taking antidepressants when indicated. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/20-of-pregnant-australian-women-dont-receive-the-recommended-mental-health-screening-139979">20% of pregnant Australian women don't receive the recommended mental health screening</a>
</strong>
</em>
</p>
<hr>
<p>Recently revised <a href="https://www.cope.org.au/health-professionals/health-professionals-3/">guidelines</a> on mental health care in the perinatal period (during pregnancy and after birth) warn health professionals against the dangers of failing to prescribe necessary medication:</p>
<blockquote>
<p>Be aware that failure to use medication where indicated for depression and/or anxiety in pregnancy or postnatally may affect mother-infant interaction, parenting, mental health and wellbeing and infant outcomes.</p>
</blockquote>
<p>These guidelines also recommend repeated screening for symptoms of depression and anxiety for all women during the perinatal period. This is crucial to providing women with an early referral to perinatal mental health services if needed.</p>
<p>At present, mental health conditions during pregnancy and after birth often go undetected and untreated. </p>
<figure class="align-center ">
<img alt="A pregnant woman talks to a therapist." src="https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564784/original/file-20231211-26-u02x0q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">There are a range of treatment options for perinatal anxiety and depression.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/depressed-pregnant-woman-consultation-psychologist-2064159131">Pormezz/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Supporting perinatal mental health</h2>
<p>Mental illness in pregnancy is a significant public health problem. Screening is not always <a href="https://theconversation.com/20-of-pregnant-australian-women-dont-receive-the-recommended-mental-health-screening-139979">delivered effectively</a>, and currently, there is <a href="https://www.aihw.gov.au/reports/mothers-babies/data-opportunities-in-perinatal-mental-health-scre/contents/about">no national data</a> regarding perinatal mental health screening service use or outcomes. </p>
<p>Mine and my colleagues’ <a href="https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-019-2320-9">research</a> on pregnant women’s engagement with perinatal mental health services indicated only one-third of eligible women accepted a referral, and less than half attended their appointment. Women may be reluctant to engage due to stigma, time restraints, and lack of childcare or social support.</p>
<p>To address this, we should create strategies and resources in collaboration with pregnant women to identify solutions that work best for them. This might include assistance with childcare, access to telehealth, visits from a perinatal mental health professional, or written information on medications. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/considering-going-off-antidepressants-heres-what-to-think-about-first-198880">Considering going off antidepressants? Here's what to think about first</a>
</strong>
</em>
</p>
<hr>
<p>Care must be holistic and include partners who may be best placed to support pregnant women in making complex decisions. Health-care providers need to be respectful of individual needs and provide compassionate care to engage vulnerable mothers who may understandably feel uncertain regarding their options.</p>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14.</em></p><img src="https://counter.theconversation.com/content/218045/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alka Kothari does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Guidelines on mental health during pregnancy and after birth emphasise antidepressants should be prescribed if they’re needed.Alka Kothari, Associate Professor, Faculty of Medicine, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2114202023-12-13T19:04:04Z2023-12-13T19:04:04ZAI can already diagnose depression better than a doctor and tell you which treatment is best<figure><img src="https://images.theconversation.com/files/563806/original/file-20231206-29-djskol.jpg?ixlib=rb-1.1.0&rect=28%2C9%2C6339%2C4229&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-patient-lying-on-ct-mri-1948882015">Shutterstock</a></span></figcaption></figure><p>Artificial intelligence (AI) is poised to revolutionise the way we diagnose and treat illness. It could be particularly helpful for depression because it could make more accurate diagnoses and determine which treatments are more likely to work. </p>
<p>Some <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2671413">20% of us</a> will have depression at least once in our lifetimes. Around the world,
<a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32279-7/fulltext">300 million</a> people are currently experiencing depression, with <a href="https://www.abs.gov.au/statistics/health/mental-health/national-study-mental-health-and-wellbeing/2020-2022">1.5 million</a> Australians likely to be depressed at any one time. Because of this, depression has been described by the <a href="https://iris.who.int/bitstream/handle/10665/254610/W?sequence=1">World Health Organization</a> as the single biggest contributor to ill health around the world. </p>
<p>So how exactly could AI help?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/depression-isnt-just-sadness-its-often-a-loss-of-pleasure-210429">Depression isn't just sadness – it's often a loss of pleasure</a>
</strong>
</em>
</p>
<hr>
<h2>Depression can be hard to spot</h2>
<p>Despite its frequency, depression is difficult to diagnose. So hard, in fact, that general practitioners accurately detect depression in <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60879-5/fulltext">less than half</a> of cases.</p>
<p>This is because there is no one test for depression: doctors use self-reported symptoms, questionnaires and clinical observations to make a diagnosis. But <a href="https://www.mayoclinic.org/diseases-conditions/depression/symptoms-causes/syc-20356007">symptoms of depression</a> are not the same for everyone. Some people may sleep more, others sleep less; some people lack energy and interest in activities, while others may feel sad or irritable. </p>
<p>For those who are accurately diagnosed with depression, there are a range of <a href="https://www.blackdoginstitute.org.au/resources-support/depression/treatment/">treatment options</a> including talk therapy, medications and lifestyle change. However, response to treatment is different for each person, and we have no way to know ahead of time which treatments will work and which won’t. </p>
<p>AI trains computers to think like humans, with a particular focus on three human-like behaviours: learning, reasoning and self-correction (to fine-tune and improve performance over time). One branch of AI is machine learning, the goal of which is to train computers to learn, find patterns in data and make data-informed predictions without guidance from humans. </p>
<p>In recent years there has been a surge in research applying AI to illnesses like depression, which can be difficult to diagnose and treat. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man sits with head in hands opposite clinician with clipboard checklist" src="https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/563808/original/file-20231206-20-9nfvdv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Doctors usually diagnose depression via questionnaires and self-ratings.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/people-have-stressed-problem-consultation-psychologist-1897694278">Shutterstock</a></span>
</figcaption>
</figure>
<h2>What they’ve found so far</h2>
<p>Scientists have compared <a href="https://chat.openai.com/auth/login">ChatGPT</a> diagnoses and medical recommendations to those of real-life doctors with <a href="https://fmch.bmj.com/content/11/4/e002391">surprising results</a>. When given information on fictional patients of varied depression severity, sex and socioeconomic status, ChatGPT mostly recommended talk therapy. In contrast, doctors recommended antidepressants. </p>
<p><a href="https://www.nice.org.uk/guidance/ng222">US</a>, <a href="https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19---antidepressants-and-depression.pdf?sfvrsn=ddea9473_5">British</a> and <a href="https://www.tg.org.au/">Australian</a> guidelines recommend talk therapy as the first treatment option ahead of medication. </p>
<p>This suggests ChatGPT may be more likely to follow clinical guidelines, whereas GPs may have a tendency to <a href="https://theconversation.com/are-antidepressants-over-prescribed-in-australia-11788">overprescribe</a> antidepressants. </p>
<p>ChatGPT is also less influenced by sex and socioeconomic biases, while doctors are statistically <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052429">more likely to prescribe antidepressants to men</a>, especially those in blue-collar jobs. </p>
<h2>How depression affects the brain</h2>
<p>Depression affects specific parts of the brain. My research has shown that the areas of the brain affected by depression are <a href="https://www.nature.com/articles/s41398-019-0512-8">extremely similar</a> in different people. So much so, we can predict whether someone has depression or not with more than 80% accuracy just by looking at these brain structures on MRI scans. </p>
<p>Other <a href="https://www.frontiersin.org/articles/10.3389/fnagi.2022.912283/full">research</a> using advanced AI models has supported this finding, suggesting brain structure may be a helpful direction for AI-based diagnosis. </p>
<p>Studies using magnetic resonance imaging (MRI) data on <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jmri.28578?casa_token=7iqdP3r0DgoAAAAA:wyEHaiB5f-WdmIyoUGfpp6azxVuRG4VXwpXKQ6SandIbLmuslH6bnZXq9HhAiY3-famw8VwCjv_iH8k">brain function at rest</a> can also predict depression correctly more than 80% of the time. </p>
<p>However, combining functional and structural information from MRI gives the best accuracy, correctly predicting depression in over <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jmri.28650?casa_token=R-RQBGPfnqYAAAAA:5Ya81irf7UquSLWfBGYj919hFsYgBxXp2MicrqEMFyw4kfmTO6bxRcd2TdFM1FPQxsd8_-Ffw4DRx8Q">93% of cases</a>. This suggests using multiple brain imaging techniques for AI to detect depression may be the most viable way forward.</p>
<p>MRI-based AI tools are currently only used for research purposes. But as MRI scans become cheaper, faster and more <a href="https://www.science.org/content/article/mri-all-cheap-portable-scanners-aim-revolutionize-medical-imaging">portable</a>, it’s likely this kind of technology will soon be part of your doctor’s <a href="https://bmcmededuc.biomedcentral.com/articles/10.1186/s12909-023-04698-z#:%7E:text=Results,performance%20in%20several%20healthcare%20aspects.">toolkit</a>, helping them to improve diagnosis and enhance patient care. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/transcranial-magnetic-stimulation-can-treat-depression-developing-research-suggests-it-could-also-help-autism-adhd-and-ocd-211417">Transcranial magnetic stimulation can treat depression. Developing research suggests it could also help autism, ADHD and OCD</a>
</strong>
</em>
</p>
<hr>
<h2>The diagnostic tools you might have already</h2>
<p>While MRI-based AI applications are promising, a simpler and easier method of detecting depression may be at hand, quite literally. </p>
<p>Wearable devices like smart watches are being investigated for their ability to <a href="https://www.nature.com/articles/s41746-023-00828-5">detect and predict</a> depression. Smart watches are especially helpful because they can collect a wide variety of data including heart rate, step counts, metabolic rate, sleep data and social interaction. </p>
<p>A recent <a href="https://www.nature.com/articles/s41746-023-00828-5#Sec2">review</a> of all studies done so far on using wearables to assess depression found depression was correctly predicted 70–89% of the time. Since they are commonly used and worn around the clock, this research suggests wearable devices could provide unique data that might otherwise be hard to collect. </p>
<p>There are some <a href="https://www.thelancet.com/journals/landig/article/PIIS2589-7500(22)00194-7/fulltext">drawbacks</a>, however, including the substantial cost of smart devices which may be inaccessible to many. Others include the questioned ability of smart devices to detect biological data in <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2029240">people of colour</a> and the <a href="https://www.nature.com/articles/s41746-021-00408-5">lack of diversity</a> in study populations. </p>
<p>Studies have also turned to social media to detect depression. Using AI, scientists have predicted the presence and severity of depression from the <a href="https://journals.sagepub.com/doi/10.1177/0165551517740835">language of our posts and community memberships</a> on social media platforms. The specific words that were used predicted depression with up to <a href="https://www.sciencedirect.com/science/article/abs/pii/S0933365723002300">90% success</a> rates in both English and Arabic. Depression has also been successfully detected in its early stages from the <a href="https://www.sciencedirect.com/science/article/abs/pii/S2468696422000283">emojis we use</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man's hands tipping out one capsule with glass of water nearby on table" src="https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/563811/original/file-20231206-29-s2excn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Doctors are statistically more likely to prescribe antidepressants to men.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-man-feeling-stressed-depressed-takes-2337502457">Shutterstock</a></span>
</figcaption>
</figure>
<h2>Predicting responses to treatment</h2>
<p>Several studies have found antidepressant <a href="https://prcp.psychiatryonline.org/doi/10.1176/appi.prcp.20220015">treatment response</a> <a href="https://www.nature.com/articles/s41746-023-00817-8#Sec6">could be predicted</a> with more than 70% accuracy from electronic health records alone. This could provide doctors with more accurate evidence when prescribing medication-based treatments. </p>
<p>Combining data from people in trials for antidepressants, scientists have <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00471-X/fulltext">predicted</a> whether taking medications will help specific patients go into remission from depression.</p>
<p>AI shows substantial promise in the diagnosis and management of depression, however recent findings require validation before they can be relied upon as diagnostic tools. Until then, MRI scans, wearables and social media may be helpful to assist doctors diagnose and treat depression.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/netflix-psychiatrist-phil-stutz-says-85-of-early-therapy-gains-are-down-to-lifestyle-changes-is-he-right-195567">Netflix psychiatrist Phil Stutz says 85% of early therapy gains are down to lifestyle changes. Is he right?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/211420/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Hellewell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Research suggests AI could diagnose depression from health records or even social media posts. And it could overcome GP bias when it comes to prescribing medications.Sarah Hellewell, Research Fellow, Faculty of Health Sciences, Curtin University, and The Perron Institute for Neurological and Translational Science, Curtin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2160252023-10-23T13:43:49Z2023-10-23T13:43:49ZHow antidepressants, ketamine and psychedelic drugs may make brains more flexible – new research<figure><img src="https://images.theconversation.com/files/555238/original/file-20231023-19-78v8r3.jpg?ixlib=rb-1.1.0&rect=263%2C203%2C7724%2C5784&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/neurons-marked-by-fluorescence-354063143">Juan Gaertner/Shutterstock</a></span></figcaption></figure><p>The first-line pharmacological treatment for major depressive disorder (MDD) are antidepressant drugs known as selective serotonin re-uptake inhibitors (SSRIs). But a significant proportion of people <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3363299/">don’t respond</a> to these drugs. </p>
<p>Given that major depression is a global mental health problem that is <a href="https://www.nature.com/articles/475027a">on the increase</a>, it is important to find novel pharmacological treatments for those who do not respond to the current ones. But to do that, we need to understand exactly how the drugs work – which we currently don’t.</p>
<p>MDD is a debilitating and distressing mental health disorder, trapping sufferers in a rigid and negative state of mind. There’s even evidence suggesting that this lack of flexibility is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238070/">associated with cognitive changes</a>, including negative thoughts and biases, and problems with learning and memory.</p>
<p>In our new study, <a href="https://www.nature.com/articles/s41380-023-02285-8">published in Molecular Psychiatry</a>, we show that an SSRI called ecitalopram may actually make brains more “plastic” – meaning more flexible and adaptive; more able to facilitate communication between neurons (brain cells). Brain plasticity is simply the ability of neural circuits to change through growth and reorganisation. Learning involves brain plasticity, including changes in neural circuits, and can help people to recover from depression.</p>
<p>One novel treatment option for depression, approved by the US Food and Drug Administration, is intranasal esketamine (an anaesthetic made from ketamine), although it has not as yet been approved for use by the NHS. The psychedelic drugs LSD and psilocybin <a href="https://pubmed.ncbi.nlm.nih.gov/31636488/">are also being investigated</a> for treatment resistant depression in research studies, but are not yet approved by regulatory bodies. When these studies are conducted, there is careful monitoring by a medical professional to ensure participant safety.</p>
<p>We know that both SSRIs and psychedelics <a href="https://www.sciencedirect.com/science/article/pii/S0028390822003161">target the same brain receptor</a> (known as the 5HT-2A). By contrast, eskatamine, similar to ketamine, works on a different receptor (N-methyl-D-aspartate or NMDA) and affects the brain chemical glutamate.</p>
<p>So how do SSRIs and psychedelics work to reduce symptoms of depression? At present, we don’t have the full picture. But the 5HT-2A receptor is linked to the brain chemical serotonin, increasing levels of it in the brain. And a recent study has indeed shown that serotonin <a href="https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01704-8/fulltext">appears to be reduced</a> in people with depression.</p>
<p>SSRIs, however, also affect the neurotransmitters GABA and glutamate. The latter has been linked to learning, cognition and memory – suggesting SSRI may actually <a href="https://pubmed.ncbi.nlm.nih.gov/33657450/">help to restore cognitive function</a>. Although the exact mechanisms of psychedelics are not yet fully understood, their antidepressant effects seem to work in a similar way to SSRIs given their effects on 5HT-2A receptors. However, there are also <a href="https://link.springer.com/article/10.1007/s40263-021-00877-y">other reactions</a> to psychedelics, such as hallucinations.</p>
<h2>Measuring brain plasticity</h2>
<p>All these drugs have therefore been suggested to affect brain plasticity. However, in humans, it can be difficult to estimate levels of brain plasticity. One common method that scientists have used is to measure a protein called the brain-derived neurotrophic factor (BDNF) in blood samples. </p>
<p>BDNF helps <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/">brain plasticity</a> by increasing the number of synapses (locations where neurons can communicate with each other), as well as the branches and growth of developing neurons. Synapses are particularly important in brain functioning as they allow transmission of chemical and electrical signals from one neuron to another. Similarly, synapses also store brain chemicals for release. </p>
<p>There have been some studies <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328267/#:%7E:text=While%20both%20SSRIs%20and%20SNRIs,0.93%3B%20P%20%3D%200.009">showing that</a> antidepressant drugs increase BDNF. However, better techniques are required to study plasticity in the human brain. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Antidepressant pill with smiling face in blister pack." src="https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555242/original/file-20231023-25-dkmk19.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">It is unknown exactly how SSRIs treat depression.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antidepressant-pill-smiling-face-blister-pack-786910729">DestinaDesign-Shutterstock</a></span>
</figcaption>
</figure>
<p>To develop better drugs, one approach is to find anti-depressant drugs with a faster mechanism of action. According to the NHS website, SSRIs <a href="https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/overview/#:%7E:text=When%20they're%20prescribed%2C%20you,t%20stop%20taking%20the%20medicine">usually need to be taken</a> for two to four weeks before any benefit is felt. </p>
<p>We suspected that one reason for this delayed effect may be that brain plasticity needs to occur with SSRI treatment. As this process involves rewiring, such as the creation of synapses and circuits, it isn’t instant, but <a href="https://www.sciencedirect.com/science/article/pii/S0306452204005366?casa_token=YYK8O5aH_CYAAAAA:yHDNSHP6HJjbMelk3gvE-WGnvgeHkzusUszIhnS8TySOUH9gK2B2q3rt38QB8lj-uEAR3QtEPg">is thought to take</a> approximately 14-21 days.</p>
<p>In our study, which was a collaboration between the University of Cambridge and the University of Copenhagen, we used a novel technique to measure plasticity in the human brain, following SSRI treatment, for the first time. </p>
<p>Thirty-two participants underwent positron emission tomography (PET) scanning to detect the amount of a protein called “synaptic vesicle glycoprotein 2A”, or SV2A, in the brain. We know that <a href="https://www.science.org/doi/full/10.1126/scitranslmed.aaf6667?casa_token=MyIx6zmoLm8AAAAA:TKIwzV_Xlsi4_3Ny40uwK-WWaUKHzSJUIyDGQw8byzbhG_B38Gk2sGmhR6zap7B1ARr36NUaynmZOA">SV2A is a marker</a> of the presence of synapses. An increased amount would suggest that more synapses are present and therefore that brain plasticity is higher. </p>
<p>Our results showed a rise in this protein as a result of taking escitalopram (an SSRI). We found that, in those taking escitalopram, increased SV2A was associated with increased duration on the drug. Our findings suggest that brain plasticity increases over three to five weeks in healthy humans following daily intake of escitalopram. </p>
<p>This is the first real evidence in humans that SSRIs really do boost neuroplasticity – seen in the brain – and that this is one of the reasons it can treat depression. Similar evidence from studies in the human brain are still required for the psychedelics. </p>
<p>It makes sense that if antidepressant treatment facilitates brain plasticity, this should make it easier for people taking these treatments to learn new things. And we know that the ability to adopt new strategies, and change them if they don’t work (supported by what researchers call cognitive flexibility), is <a href="https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ee3e78f5e20bd9019d41a4e820bbdb597ac9a2d8">key to recovering from depression</a>.</p><img src="https://counter.theconversation.com/content/216025/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Barbara Jacquelyn Sahakian receives funding from the Leverhulme Trust and the Lundbeck Foundation. Her research work is conducted within the NIHR Cambridge Biomedical Research Centre (BRC) Mental Health and Neurodegeneration Themes and the NIHR MedTech and in vitro diagnostic Co-operative (MIC). She consults for Cambridge Cognition.</span></em></p><p class="fine-print"><em><span>Christelle Langley receives funding from the Leverhulme Trust. Her research work is conducted within the NIHR Cambridge Biomedical Research Centre (BRC) Mental Health and Neurodegeneration Themes and the NIHR MedTech and in vitro diagnostic Co-operative (MIC).</span></em></p>It is unknown exactly how SSRIs and psychedelics treat depression, but their ability to boost flexibility may be more important than previously thought.Barbara Jacquelyn Sahakian, Professor of Clinical Neuropsychology, University of CambridgeChristelle Langley, Postdoctoral Research Associate, Cognitive Neuroscience, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2119912023-08-31T16:38:29Z2023-08-31T16:38:29ZZuranolone for postpartum depression: Hope, hype or both?<figure><img src="https://images.theconversation.com/files/545577/original/file-20230830-29-opoz13.jpg?ixlib=rb-1.1.0&rect=343%2C49%2C3084%2C2103&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While zuranolone represents an exciting advance in the treatment of postpartum depression, many questions about its potential impact remain unanswered. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/zuranolone-for-postpartum-depression-hope-hype-or-both" width="100%" height="400"></iframe>
<p>While mothers with <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/postpartum-depression">postpartum depression</a> have always faced barriers accessing the care they need, things have been particularly bad since the onset of the COVID-19 pandemic. </p>
<p>Prior to COVID-19, it was thought that up to <a href="https://www.ncbi.nlm.nih.gov/books/NBK37740/">one in five</a> women would develop depression in the first postpartum year, but the stresses and service disruptions associated with the pandemic increased this to <a href="https://doi.org/10.1016/S2215-0366(21)00074-2">one in three</a>. However, the pandemic also coincided with a period of significant innovation in treatment that may increase access to and effectiveness of care.</p>
<h2>Medications specifically for PPD</h2>
<p>One exciting development was the United States Food and Drug Administration’s approval of the medication brexanolone in <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-post-partum-depression">early 2019</a>. It represented the first of an entirely new class of medicines for postpardum depression (PPD), which target the steep decrease in hormones after delivery. Brexanolone is a synthetic version of allopregnanolone, a naturally occurring substance made from progesterone, that helps the brain regulate stress. </p>
<p>Its approval in the U.S. was especially notable for two reasons: it was the first medicine approved specifically for the treatment of PPD, and it takes effect especially quickly — within 60 hours. </p>
<p>While it represents a significant breakthrough, it must be given intravenously in hospital over 2½ days, and <a href="https://www.cbc.ca/news/health/zulresso-postpartum-depression-1.5064086">can cost as much as USD$34,000</a> per course.</p>
<figure class="align-center ">
<img alt="Out-of-focus image of exhausted woman sitting on the floor beside a crib" src="https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/545573/original/file-20230830-27-ye7dqi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">During the pandemic, as many as one in three new mothers may have experience postpartum depression.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>On Aug. 4, the U.S. FDA <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression">approved zuranolone</a>, another allopregnanolone derivative. Unlike brexanolone, zuranolone can be taken in pill form over two weeks, which is much shorter than traditional antidepressants which are usually prescribed for several months. </p>
<p>Early studies of zuranolone suggest PPD symptom improvement can be observed <a href="https://doi.org/10.1001/jamapsychiatry.2021.1559">as early as three days</a> after starting the treatment. This is an unusually rapid response to an antidepressant medication, which usually <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/antidepressant-medications">take effect over several weeks</a>. </p>
<h2>Behind the hype</h2>
<p>The <a href="https://www.vogue.com/article/zuranolone-postpartum-depression-explainer">fanfare</a> that <a href="https://www.cbc.ca/radio/thecurrent/postpartum-depression-pill-zuranolone-offers-hope-1.6935868">has accompanied</a> these <a href="https://www.cnn.com/2019/03/19/health/postpartum-depression-drug-fda-bn/index.html">medications</a> also has the potential to increase awareness of PPD, suggesting a biological explanation for a condition associated with <a href="https://doi.org/10.1080/02646838.2020.1754372">so much self-blame</a>, encouraging more people to seek treatment and increasing screening and detection efforts among health-care providers. </p>
<p>If approved in Canada, it would also add to the array of effective treatments that already exist. These include evidence-based talking therapies like cognitive behavioural therapy and interpersonal psychotherapy, which are <a href="https://journals.sagepub.com/doi/epub/10.1177/0706743716659276">first-line treatments</a> for mild to moderate PPD. </p>
<p>Antidepressant medications like the <a href="https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/overview/">selective serotonin re-uptake inhibitors</a> (SSRIS, such as sertraline and escitalopram) are also widely available and usually recommended as second-line therapies for most individuals with PPD. </p>
<figure class="align-center ">
<img alt="Photo of a smartphone screen displaying a New York Times story about a new PPD medication" src="https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=423&fit=crop&dpr=1 754w, https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=423&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/545574/original/file-20230830-16-b7bnss.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=423&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The fanfare surrounding new medications for zuranolone also has the potential to increase awareness of PPD.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Although psychotherapy and antidepressants can help most individuals with PPD, timely access to talking therapies is relatively rare within publicly funded health-care systems, and many <a href="https://doi.org/10.1111/j.1523-536X.2006.00130.x">prefer to avoid</a> antidepressant medications during pregnancy and lactation if they can.</p>
<p>While zuranolone represents an exciting advance, many questions about its potential impact remain unanswered. </p>
<p>To date, just <a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20220785">two clinical trials</a> <a href="https://doi.org/10.1001/jamapsychiatry.2021.1559">in humans exist</a>, and eligibility for these studies was restricted to a very small subset of those with PPD. Only individuals with more severe depression that emerged between the third trimester of pregnancy and four weeks post-delivery could be enrolled. </p>
<p>Researchers also only studied zuranolone’s effects over six weeks, and no information on its safety during pregnancy and lactation is available (participants had to agree to stop breastfeeding while taking the medication). </p>
<p>Despite the excitement surrounding its U.S. approval, the cost of zuranolone is likely to be high, and it is not known if it will be approved in Canada. Finally, it is unclear if this medication will be covered by public or private insurers, which could put it out of reach for many with PPD who could need it the most. </p>
<h2>PPD is still underdiagnosed</h2>
<p>The development of innovative new medications is exciting and can generate significant hope for those affected. However, it is important in this case that we not lose sight of the fact that PPD is a <a href="https://doi.org/10.1017/S1092852914000510">vastly underdetected and undertreated problem</a> for which safe and effective treatments already exist. </p>
<figure class="align-center ">
<img alt="Two women pushing strollers in park, seen from behind" src="https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/545575/original/file-20230830-24-3j5cxd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Inexpensive self-care interventions like improving social and practical supports, sleep hygiene, relaxation techniques, exercise and taking time for oneself can also be helpful.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Free screening tools such as the <a href="http://www.perinatalservicesbc.ca/Documents/Resources/HealthPromotion/EPDS/EPDSQuestionnaireApril2013.pdf">Edinburgh Postnatal Depression Scale</a> can be used to help detect PPD, and psychotherapy along with several existing antidepressants <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/postpartum-depression">can be effective and safe</a> during pregnancy and lactation.</p>
<p>Inexpensive <a href="https://www.canada.ca/en/public-health/services/child-infant-health/postpartum-health-guide.html#a1.6">self-care interventions</a> like improving social and practical supports, sleep hygiene, relaxation techniques, exercise and taking time for oneself can also be helpful, but can be challenging to engage in with a newborn. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/heart-rate-variability-and-self-compassion-two-tools-to-help-postpartum-mothers-make-exercise-decisions-193548">Heart rate variability and self-compassion: Two tools to help postpartum mothers make exercise decisions</a>
</strong>
</em>
</p>
<hr>
<p>Although provincially funded psychotherapy can be difficult to access, research and <a href="https://www.stcatharinesstandard.ca/life/health-wellness/mothers-experiencing-postpartum-depression-aided-by-online-therapy-delivered-by-niagara-public-health-nurses/article_238ee7dd-6b7b-5165-b6e7-1b80cdcc252a.html">efforts to apply findings</a> are starting to bring together the fragmented network of community organizations and traditional and public health services to try to increase access in Canada. </p>
<p>Research into treatments for PPD and the federal government’s actions in appointing a <a href="https://www.pm.gc.ca/en/mandate-letters/2021/12/16/minister-mental-health-and-addictions-and-associate-minister-health">Minister of Mental Health and Addictions</a> and prioritizing perinatal parents are also cause for genuine optimism. </p>
<p>While zuranolone is raising awareness about PPD, it’s important to <a href="https://www.ourcommons.ca/Content/Committee/441/FEWO/Brief/BR11978299/br-external/VanLieshoutRyan-Brief-e.pdf">highlight the need</a> to develop national quality standards and Canadian-specific stepped-care models and care pathways. That would enable people to access existing treatments in a more timely manner, which would go a long way in helping Canada become the best country in the world to have a baby.</p><img src="https://counter.theconversation.com/content/211991/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ryan Van Lieshout receives funding from The Canada Research Chairs Program, The Canadian Institutes of Health Research, and The Daymark Foundation. </span></em></p>Amid the fanfare about a new medication for postpartum depression, it’s important to remember that PPD is underdiagnosed and undertreated, and that safe and effective treatments already exist.Ryan Van Lieshout, Canada Research Chair in Perinatal Mental Health, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2092002023-08-28T12:01:17Z2023-08-28T12:01:17ZMedication can help you make the most of therapy − a psychologist and neuroscientist explains how<figure><img src="https://images.theconversation.com/files/544648/original/file-20230824-2975-7ib62y.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1917%2C1564&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Medications can open a biological window of opportunity for psychotherapy to take advantage of.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/metaphor-bipolar-disorder-mind-mental-double-royalty-free-illustration/1294477039">melitas/iStock via Getty Images Plus</a></span></figcaption></figure><p>There is mounting recognition in the scientific community that combining different treatment approaches for mental health conditions can <a href="https://doi.org/10.1016/j.biopsych.2018.09.004">create a benefit</a> greater than the sum of its parts.</p>
<p>As a <a href="http://www.canlab.pitt.edu/home/people/">clinical psychologist</a> and <a href="https://scholar.google.com/citations?user=7wB91zsAAAAJ&hl=en">neuroscience researcher</a>, I have been working to integrate insights from both fields to expand treatment options for those suffering from depression, anxiety and related conditions. Designing a treatment plan that pays careful attention to the sequence and dose of both biological and behavioral therapies might benefit people in new ways that neither approach can achieve on its own.</p>
<p><a href="https://doi.org/10.1093/ije/dyu038">Anxiety and depression</a> are the most prevalent mental health conditions around the world. Globally, <a href="https://www.who.int/news-room/fact-sheets/detail/depression">about 280 million people</a> experience depression, and <a href="https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder">as many as 1 in 3</a> will meet the diagnostic criteria for an anxiety disorder at some point in their lives. There are <a href="https://www.nhs.uk/mental-health/conditions/depression-in-adults/treatment/">numerous effective</a> <a href="https://www.nhs.uk/mental-health/conditions/anxiety/types-of-anxiety/">treatment options</a> for both conditions, including medications, psychotherapy, lifestyle changes and neurostimulation. </p>
<p>Doctors and therapists recommend many patients seeking mental health care try <a href="https://evidence.nihr.ac.uk/alert/combined-drug-and-psychological-therapies-may-be-most-effective-for-depression/">more than one approach simultaneously</a>, such as medication and therapy. This is based on the idea that if they were to respond well to any of the prescribed treatments, they would experience a net benefit more quickly or more strongly than if they were to try each sequentially. However, researchers have historically studied each approach in isolation. Most research has focused on comparing individual treatments <a href="https://doi.org/10.1002/wps.20701">one at a time</a> to a control, such as a pill placebo or a psychotherapy waitlist.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/z-IR48Mb3W0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Depression is a leading cause of disability around the world.</span></figcaption>
</figure>
<h2>Neuroplasticity and treatment</h2>
<p>Recent advances in scientific understanding of <a href="https://doi.org/10.1016/j.biopsych.2021.05.008">depression</a>, <a href="https://doi.org/10.2147/IJGM.S413176">anxiety</a> and <a href="https://doi.org/10.1016/j.mehy.2005.05.007">other stress-related conditions</a> suggest that changes and impairments in neuroplasticity are critical contributors.</p>
<p>Neuroplasticity refers to the brain’s capacity to flexibly adjust in response to an ever-changing environment – it’s a <a href="https://theconversation.com/cognitive-flexibility-is-essential-to-navigating-a-changing-world-new-research-in-mice-shows-how-your-brain-learns-new-rules-204259">critical component of learning</a>. In animal studies, deficits in neuroplasticity are seen as changes to molecular and neural pathways, such as a decreased number of synapses, or points of contact between neurons, following chronic stress. These changes might be related to <a href="https://doi.org/10.1038/s41380-019-0615-x">mental patterns and symptoms</a> of depression and anxiety in people, such as when patients report a reduced capacity to think, feel and act flexibly. They may also be linked to thinking about, remembering and interpreting information in a way that tends to be biased toward the negative.</p>
<p>Research has shown that many effective biological treatments, including medications and neurostimulation, can <a href="https://doi.org/10.1038/tp.2013.30">enhance or</a> <a href="https://doi.org/10.1016/j.biopsych.2021.05.008">alter neuroplasticity</a>. Certain lifestyle changes such as regular exercise can have similar effects. Scientists consider this key to how they reduce symptoms. Unfortunately, symptoms often return when these treatments are discontinued. Relapse is particularly apparent for medications. For both <a href="https://doi.org/10.1038/s41380-022-01824-z">older</a> and <a href="https://doi.org/10.1001/jamapsychiatry.2019.1189">newer</a> antidepressant and anti-anxiety medications, relapse rates begin climbing shortly after patients stop treatment.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of hand holding pill beside a glass of water on a table" src="https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/544652/original/file-20230824-27-homnj8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Patients can experience a relapse of symptoms after they stop taking antidepressants or anti-anxiety medications.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/unrecognizable-man-holding-a-pill-in-front-of-a-royalty-free-image/1297835134">Vasil Dimitrov/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>In contrast, behavioral treatments such as psychotherapy introduce new skills and and habits that <a href="https://doi.org/10.1146/annurev.psych.57.102904.190044">may be more long-lasting</a>. Benefits continue even after the most intense phase of treatment ends. Regular meetings <a href="https://theconversation.com/cbt-dbt-psychodynamic-what-type-of-therapy-is-right-for-me-171101">with a therapist</a> over the course of several months can help many patients learn to cope with negative symptoms and life circumstances in new ways. But such learning depends on neuroplasticity to forge and retain these new, helpful pathways in the brain.</p>
<p>Researchers hypothesize that enhancing or modulating plasticity with a biological intervention like medication may not only reduce symptoms but may also provide a <a href="https://doi.org/10.1016/j.biopsych.2018.09.004">window of opportunity</a> for behavioral interventions like psychotherapy to be more effective. Learning-based interventions like cognitive-behavioral or exposure therapy, if properly timed, could harness the enhanced neuroplasticity that biological interventions induce and improve long-term outcomes.</p>
<p>Think of pathways in the brain as roads. Biological treatments transform a sparsely connected set of roads – consisting only of a few well-trodden pathways that represent unhelpful thoughts, fears and habits – into a denser network of interconnected, freshly paved roadways. Behavioral treatments can be likened to repeatedly driving over a specific subset of new roads that lead to more balanced perspectives on yourself and the world around you, learning them until you can drive down them effortlessly, no GPS required. This ensures that those now familiar roadways will be readily available to you in the future and protect you against the return of anxiety and depression.</p>
<h2>Synergies in combined treatment</h2>
<p>Designing combined treatments to explicitly promote synergy is relatively new, and there is increasing evidence supporting it. A few specific examples are noteworthy.</p>
<p>First, some studies have shown that <a href="https://doi.org/10.1097%2FHRP.0000000000000183">D-cycloserine</a>, an antibiotic used to treat tuberculosis, may make <a href="https://doi.org/10.1001/jamapsychiatry.2016.3955">exposure therapy for anxiety conditions</a> more effective by helping patients learn to quell their fears. D-cycloserine may also enhance the antidepressant effects of a type of neurostimulation called <a href="https://doi.org/10.1001/jamapsychiatry.2022.3255">transcranial magnetic stimulation</a>, which stimulates nerve cells using magnetic fields.</p>
<p>Several studies suggest that pairing neurostimulation with cognitive-behavioral approaches like cognitive-behavioral therapy or cognitive control training may yield <a href="https://doi.org/10.1016/j.biopsych.2018.09.004">longer-term reductions in depression and anxiety</a>.</p>
<p>Similarly, low doses of ketamine, a drug used in general anesthesia, with rapid antidepressant effects, can be used to “<a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20220216">prime the pump</a>” <a href="https://theconversation.com/ketamine-paired-with-looking-at-smiling-faces-to-build-positive-associations-holds-promise-for-helping-people-with-treatment-resistant-depression-190950">for new, helpful learning</a>. A study my team and I conducted found that daily computer-based exercises of 30 to 40 minutes over four days following a single ketamine dose led to a ninefold increase in the duration of antidepressant effects – <a href="https://doi.org/10.1001/jamanetworkopen.2023.12434">90 days of reduced symptoms</a> – compared with ketamine alone, which led to 10 days of reduced symptoms.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/dYN64GJzGfc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Researchers are exploring the potential of psychedelics to treat many mental health conditions.</span></figcaption>
</figure>
<p>Finally, there is increasing interest in using other medications with psychedelic properties to assist in psychotherapy. The therapeutic benefits of taking these <a href="https://doi.org/10.1007/s11920-022-01363-y">psychedelic-assisted therapies</a> under medical supervision are attributed to the rapid <a href="https://doi.org/10.1523/JNEUROSCI.1121-22.2022">neuroplasticity-enhancing</a> and consciousness-altering effects of drugs like psilocybin and MDMA. Researchers think these short-term effects foster new insights and perspectives that psychotherapists can help patients integrate into their permanent worldview.</p>
<p>There is great potential in neuroscience-guided ways to combine treatments. However, it’s important to note that different treatment approaches can occasionally work against each other, <a href="https://doi.org/10.1016/S0272-7358(97)00084-6">lessening the long-term benefits of psychotherapy alone</a>. For example, one study on panic disorder found that patients who learned psychotherapy techniques while taking anti-anxiety medication had a <a href="https://jamanetwork.com/journals/jama/fullarticle/192707">greater chance of relapse</a> after discontinuing their use compared with those given psychotherapy alone.</p>
<p>Carefully designed clinical trials and long-term follow-ups are needed to fully understand how to combine the biological and the behavioral to develop treatments that are efficient, accessible, safe and enduring.</p><img src="https://counter.theconversation.com/content/209200/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Price receives funding from the National Institute of Mental Health and the Laurel E. Zaks Memorial Research Fund and is named as the inventor on a University of Pittsburgh-owned patent filing relevant to synergistic bio-behavioral treatments for anxiety and depression.</span></em></p>Combining psychotherapy with medication can lead to more immediate and enduring results by boosting the brain’s neuroplasticity.Rebecca Price, Associate Professor of Psychiatry and Psychology, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2059632023-08-15T09:14:14Z2023-08-15T09:14:14ZScience experiments traditionally only used male mice – here’s why that’s a problem for women’s health<figure><img src="https://images.theconversation.com/files/532978/original/file-20230620-25-ktr7u.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5967%2C4158&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/small-experimental-mouse-on-laboratory-researchers-605226554">unoL/Shutterstock</a></span></figcaption></figure><p>If you have ever taken a medicine, then you have benefited from research in animals. But ten years ago, if you looked at a scientific report involving mice or rats, it would probably have used only male animals.</p>
<p>This means that, even now, if you’re a woman and the medicine has only been developed and tested using male animals, we don’t know how that medicine is going to affect you.</p>
<iframe id="noa-web-audio-player" style="border: none" src="https://embed-player.newsoveraudio.com/v4?key=x84olp&id=https://theconversation.com/science-experiments-traditionally-only-used-male-mice-heres-why-thats-a-problem-for-womens-health-205963&bgColor=F5F5F5&color=D8352A&playColor=D8352A" width="100%" height="110px"></iframe>
<p>Scientists long assumed that <a href="https://books.google.co.uk/books?hl=en&lr=&id=KDicAgAAQBAJ&oi=fnd&pg=PT19&ots=SWnevYYdZn&sig=yWbWfMXIzm32BhXKVG984Lgs-3Y&redir_esc=y#v=onepage&q&f=false">females would respond the same way as males in drug trials</a>. But today, that situation is changing. More and more studies use both female and male animals – and new science is emerging about important sex differences as a result.</p>
<p>For example, a growing body of evidence from animal studies is highlighting <a href="https://www.frontiersin.org/articles/10.3389/fnins.2020.583477/full#B110">complex sex differences in rodent brains</a>, relating to their size, shape, and how nerve cells connect with one another. </p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><em>This article is part of <a href="https://theconversation.com/uk/topics/womens-health-matters-143335">Women’s Health Matters</a>, a series about the health and wellbeing of women and girls around the world. From menopause to miscarriage, pleasure to pain the articles in this series will delve into the full spectrum of women’s health issues to provide valuable information, insights and resources for women of all ages.</em></p>
<p><em>You may be interested in:</em></p>
<p><em><a href="https://theconversation.com/five-old-contraception-methods-that-show-why-the-pill-was-a-medical-breakthrough-207572">Five old contraception methods that show why the pill was a medical breakthrough
</a></em></p>
<p><em><a href="https://theconversation.com/the-orgasm-gap-and-why-women-climax-less-than-men-208614">The orgasm gap and why women climax less than men</a></em></p>
<hr>
<p>So it’s no surprise that research is also increasingly showing sex differences in human medical issues. For example, <a href="https://pubmed.ncbi.nlm.nih.gov/12890270/">women are twice as likely as men</a> to be diagnosed with depression, and sex differences are also clear in <a href="https://pubmed.ncbi.nlm.nih.gov/30082889/">people’s response to antidepressants</a>. Women have a stronger response than men to selective serotonin reuptake inhibitors (SSRIs), whereas men have a better response to tricyclic antidepressants. </p>
<h2>Never assume</h2>
<p>Excluding females from research for so long has had worrying consequences for women’s health. One example is adverse drug reactions – the unintended consequences of taking a medicine, which can include things like nausea, headaches, seizures or heart problems.</p>
<p>Women typically have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275616/">double the risk</a> for adverse drug reactions (although men have increased risks of some side-effects). One reason is that women, on average, are smaller than men, yet the recommended dosage for many medicines is <a href="https://news.uchicago.edu/story/women-are-overmedicated-because-drug-dosage-trials-are-done-men-study-finds">based on men</a>.</p>
<p>For example, women who take <a href="https://academic.oup.com/ehjcvp/article/3/3/163/3058007?login=true">beta blockers</a>, used to treat heart problems, have higher concentrations of it in their blood. This is not only because the same amount of drug in a smaller blood volume will give you a higher concentration. Women also <a href="https://bsd.biomedcentral.com/articles/10.1186/s13293-020-00308-5">metabolise many medicines differently to men</a>, because of sex hormone levels and enzyme activity. </p>
<h2>Why were females excluded?</h2>
<p>In science, we like to reduce variability as much as possible, to have more confidence that any changes in an animal or human are because of the experimental intervention we have made.</p>
<p>Females were largely excluded from both animal and human clinical trials because of the menstrual cycle. Fluctuating hormone levels make data difficult to interpret, results more variable, and research more expensive. While males have the same sex steroid hormones, female hormone levels rise and fall. This can impact brain function and behaviour as well as female response to medication. </p>
<p>However, the rodent oestrous cycle is much shorter than in women, only four or five days long – and research over the last decade has shown that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962440/">female rat behaviour is not more variable</a> as a result. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="White laboratory mice, mother with pups" src="https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=366&fit=crop&dpr=1 600w, https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=366&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=366&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=460&fit=crop&dpr=1 754w, https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=460&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/533216/original/file-20230621-19-qag769.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=460&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">If we don’t use female mice in studies, we won’t properly understand how medicine affects women.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/white-laboratory-mice-mother-pups-which-71556859">Shutterstock/tilialucida</a></span>
</figcaption>
</figure>
<p>In part, the male-centric approach to clinical human trials was also because women of child-bearing age could be pregnant and not yet know it. The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573415/">thalidomide tragedy</a> fed into this mentality. Thalidomide was developed in the 1950s as a sedative and became a popular treatment for morning sickness – but the drug had not been tested on pregnant animals or humans.</p>
<p>Doctors soon realised thalidomide was linked to developmental abnormalities in children born to mothers taking the drug. But it was too late for the <a href="https://pubmed.ncbi.nlm.nih.gov/15172781/">estimated 10,000 infants worldwide born</a> with underdeveloped legs and arms, and other birth defects.</p>
<h2>Are things getting better?</h2>
<p>There is a growing field of research looking at the interaction between medicines and the menstrual cycle, changes during pregnancy, and hormonal contraception. For example, <a href="https://www.sciencedirect.com/science/article/pii/S105913111400137X">some anti-epileptic drugs</a> can reduce the effectiveness of hormonal contraception, while hormonal contraception can reduce the effectiveness of some anti-epileptic drugs to control seizures. But the many years that females were excluded from studies means there is still so much we don’t know. </p>
<p>Women were only legally required to be <a href="https://orwh.od.nih.gov/toolkit/recruitment/history#:%7E:text=In%201986%2C%20NIH%20established%20a,Grants%20and%20Contracts%20in%201987">included in clinical trials in the 1990s</a> in the US. Some 30 years later, research shows that about half of research participants in
clinical studies funded by the National Institutes of Health (NIH), the American medical research agency, <a href="https://orwh.od.nih.gov/in-the-spotlight/all-articles/nih-publishes-report-on-research-on-womens-health-for-fiscal-years-2019-2020">are now women</a>.</p>
<p>These policies are also evolving to integrate both biological sex (genetically defined) and gender (a person’s self-identity) into the design, analysis and reporting of clinical research. Many <a href="https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14761">scientific journals</a>
are also <a href="https://journals.physiology.org/doi/full/10.1152/ajpheart.00605.2021">joining the drive</a> to only publish studies that have considered sex in the design, analysis and reporting. </p>
<p>Meanwhile, it has taken a very long time for female mice to be part of the research picture. In 2014, the NIH, one of the largest funders of medical research in the world, <a href="https://doi.org/10.1038/509282a">announced</a> that all grant applications needed to include a balance of male and female cells and animals. This policy has since been taken up by major research funders in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475217/">other countries</a>, such as the Canadian Institutes of Health Research and the European Commission. </p>
<p>Change takes time. Timescales vary dramatically, but it often takes 10-15 years to develop a new medicine. Next there are the clinical trials, which can take a long time depending on the difficulty of recruiting participants.</p>
<p>We are moving to an era of personalised medicine, where medicines can be prescribed on the basis of an individual diagnosis, with targeted interventions based on understanding how an individual patient’s genomes (set of DNA instructions) affect treatment response. But women will miss out on many of the benefits if we don’t understand exactly how the drug they are prescribed affects females.</p><img src="https://counter.theconversation.com/content/205963/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>All views expressed in this article are the author's and not those of the organisations with which they are affiliated. Sarah Bailey receives research funding from Camurus and DevelRx, is vice-president for engagement at the British Pharmacological Society, and is the UK Bioscience Sector Coalition co-chair (academic).
</span></em></p>Clinical trial funders now insist studies use female participants. But it will still take a long time for our understanding of how medicine affects women to catch up.Sarah Bailey, Senior Lecturer, Neuropharmacology, University of BathLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2086622023-07-31T20:00:36Z2023-07-31T20:00:36ZTaking an antidepressant? Mixing it with other medicines – including some cold and flu treatments – can be dangerous<figure><img src="https://images.theconversation.com/files/538917/original/file-20230724-23-xwj07r.jpg?ixlib=rb-1.1.0&rect=44%2C0%2C7304%2C4902&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmacist-holding-medicine-box-capsule-pack-736925074">Shutterstock</a></span></figcaption></figure><p>In the depths of winter we are more at risk of succumbing to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522168/">viral respiratory infections</a> – from annoying sore throat, common cold and sinusitis, to the current resurgence of respiratory syncytial virus (RSV), influenza and COVID. </p>
<p>Symptoms of upper respiratory tract infection range in severity. They can include fever, chills, muscle or body aches, cough, sore throat, runny or stuffy nose, earache, headache, and fatigue. Most antibiotics target bacteria so are <a href="https://pubmed.ncbi.nlm.nih.gov/32495003/">not effective</a> for viral infections. Many people seek relief with over-the-counter medicines.</p>
<p>While evidence varies, guidelines suggest medicines taken by mouth (such as cough syrups or cold and flu tablets) have a <a href="https://pubmed.ncbi.nlm.nih.gov/25420096/">limited but potentially positive</a> short-term role for managing upper respiratory infection symptoms in adults and children older than 12. These include: </p>
<ul>
<li>paracetamol or ibuprofen for pain or fever </li>
<li>decongestants such as phenylephrine or pseudoephedrine</li>
<li>expectorants and mucolytics to thin and clear mucus from upper airways</li>
<li>dry cough suppressants such as dextromethorphan</li>
<li>sedating or non-sedating antihistamines for runny noses or watery eyes.</li>
</ul>
<p>But what if you have been prescribed an antidepressant? What do you need to know before going to the pharmacy for respiratory relief?</p>
<h2>Avoiding harm</h2>
<p>An audit of more than 5,000 cough-and-cold consumer enquiries to an Australian national medicine call centre found questions frequently related to drug-drug interactions (29%). An 18-month analysis showed 20% of calls <a href="https://pubmed.ncbi.nlm.nih.gov/26590496/">concerned</a> potentially significant interactions, particularly with antidepressants.</p>
<p>Australia remains in the “<a href="https://www.aihw.gov.au/mental-health/topic-areas/mental-health-%20prescriptions#Prescriptionsbytype">top ten</a>” antidepressant users in the <a href="https://stats.oecd.org/Index.aspx?DataSetCode=HEALTH_PHMC">OECD</a>. More than <a href="https://www.aihw.gov.au/mental-health/topic-areas/mental-health-prescriptions">32 million</a> antidepressant prescriptions are dispensed on the Pharmaceutical Benefits Scheme each year. </p>
<p>Antidepressants are commonly prescribed to manage symptoms of anxiety or depression but are also used in chronic pain and incontinence. They are classified primarily by how they affect chemical messengers in the nervous system. </p>
<p>These classes are: </p>
<ul>
<li><strong>selective serotonin reuptake inhibitors (SSRI)</strong> such as fluoxetine, escitalopram, paroxetine and sertraline </li>
<li><strong>serotonin and noradrenaline reuptake inhibitors (SNRI)</strong> such as desvenlafaxine, duloxetine and venlafaxine</li>
<li><strong>tricyclic antidepressants (TCA)</strong> such as amitriptyline, doxepin and imipramine</li>
<li><strong>monoamine oxidase inhibitors (MAOI)</strong> such as tranylcypromine<br></li>
<li><strong>atypical medicines</strong> such as agomelatine, mianserin, mirtazapine, moclobemide, reboxetine and vortioxetine</li>
<li><strong>complementary medicines</strong> including St John’s wort, S-adenosyl methionine (SAMe) and L-tryptophan</li>
</ul>
<p>Medicines within the same class of antidepressants have similar actions and side-effect profiles. But the molecular differences of individual antidepressants mean they may have different interactions with medicines taken at the same time. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/considering-going-off-antidepressants-heres-what-to-think-about-first-198880">Considering going off antidepressants? Here's what to think about first</a>
</strong>
</em>
</p>
<hr>
<h2>Types of drug interactions</h2>
<p>Drug interactions can be:</p>
<ul>
<li><strong>pharmacokinetic</strong> – what the body does to a drug as it moves into, through and out of the body. When drugs are taken together, one may affect the absorption, distribution, metabolism or elimination of the other </li>
<li><strong>pharmacodynamic</strong> – what a drug does to the body. When drugs are taken together, one may affect the action of the other. Two drugs that independently cause sedation, for example, may result in excessive drowsiness if taken together.</li>
</ul>
<p>There are many <a href="https://wchh.onlinelibrary.wiley.com/doi/pdf/10.1002/pnp.429">potential interactions</a> between medications and antidepressants. These include interactions between over-the-counter medicines for upper respiratory symptoms and antidepressants, especially those taken orally. </p>
<p>Concentrations of nasal sprays or inhaled medicines are generally lower in the blood stream. That means they are less likely to interact with other medicines. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Woman holds glass of water and tissue to head." src="https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538919/original/file-20230724-21-bals4w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Consult your pharmacist and only use treatments while symptoms persist.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sick-asian-woman-feeling-headache-flu-1696062472">Shutterstock</a></span>
</figcaption>
</figure>
<h2>What to watch for</h2>
<p>It’s important to get advice from a pharmacist before taking any medications on top of your antidepressant.</p>
<p>Two symptoms antidepressant users should monitor for shortly after commencing a cough or cold medicine are central nervous system effects (irritability, insomnia or drowsiness) and effects on blood pressure. </p>
<p>For example, taking a selective SSRI antidepressant and an oral decongestant (such as pseudoephedrine or phenylephrine) can cause irritability, insomnia and affect blood pressure.</p>
<p>Serotonin is a potent chemical compound produced naturally for brain and nerve function that can also constrict blood vessels. Medicines that affect serotonin are common and include most antidepressant classes, but also decongestants, dextromethorphan, St John’s wort, L-tryptophan, antimigraine agents, diet pills and amphetamines. </p>
<p><a href="https://reference.medscape.com/drug-interactionchecker">Combining drugs</a> such as antidepressants and decongestants that both elevate serotonin levels can cause irritability, headache, insomnia, diarrhoea and blood pressure effects – usually increased blood pressure. But some people experience orthostatic hypotension (low blood pressure on standing up) and dizziness.</p>
<p>For example, taking both a serotonin and SNRI antidepressant and dextromethorphan (a cough suppressant) can add up to high serotonin levels. This can also occur with a combination of the complementary medicine St John’s Wort and an oral decongestant. </p>
<p>Where serotonin levels are too high, <a href="https://pubmed.ncbi.nlm.nih.gov/15666281/">severe symptoms</a> such as confusion, muscle rigidity, fever, seizures and even death have been reported. Such symptoms are rare but if you notice any of these you should stop taking the cold and flu medication straight away and seek medical attention.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/medications-pregnant-women-should-take-avoid-and-think-about-49127">Medications pregnant women should take, avoid, and think about</a>
</strong>
</em>
</p>
<hr>
<h2>Ways to avoid antidepressant drug interactions</h2>
<p>There are a few things we can do to prevent potentially dangerous interactions between antidepressants and cold and flu treatments. </p>
<p><strong>1. Better information</strong></p>
<p>Firstly, there should be more targeted, consumer-friendly, <a href="https://www.webmd.com/interaction-checker/default.htm">online drug interaction information</a> available for antidepressant users. </p>
<p><strong>2. Prevent the spread of viral infections as much as possible</strong></p>
<p>Use the non-drug strategies that have worked well for COVID: regular hand washing, good personal hygiene, social distancing, and facemasks. Ensure adults and children are up to date with immunisations.</p>
<p><strong>3. Avoid potential drug interactions with strategies to safely manage symptoms</strong> </p>
<p>Consult your pharmacist for strategies most appropriate for you and only use cold and flu medications while symptoms persist:</p>
<ul>
<li>treat muscle aches, pain, or a raised temperature with analgesics such as paracetamol or ibuprofen</li>
<li>relieve congestion with a nasal spray decongestant </li>
<li>clear mucus from upper airways with expectorants or mucolytics</li>
<li>dry up a runny nose or watery eyes with a non-sedating antihistamine.</li>
</ul>
<p>Avoid over-the-counter cough suppressants for an irritating dry cough. Use a simple alternative such as honey, steam inhalation with a few drops of eucalyptus oil or a non-medicated lozenge instead.</p>
<p><strong>4. Ask whether your symptoms could be more than the common cold</strong> </p>
<p>Could it be influenza or COVID? Seek medical attention if you are concerned or your symptoms are not improving. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/taking-certain-opioids-while-on-commonly-prescribed-antidepressants-may-increase-the-risk-of-overdose-178262">Taking certain opioids while on commonly prescribed antidepressants may increase the risk of overdose</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/208662/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Treasure McGuire does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Antidepressants are prescribed for anxiety or depression but are also used in chronic pain and incontinence. When you get a respiratory infection, it’s important to avoid dangerous interactions.Treasure McGuire, Assistant Director of Pharmacy, Mater Health SEQ in conjoint appointment as Associate Professor of Pharmacology, Bond University and as Associate Professor (Clinical), The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2095912023-07-14T02:06:30Z2023-07-14T02:06:30ZKetamine injections for depression? A new study shows promise, but it’s one of many options<figure><img src="https://images.theconversation.com/files/537183/original/file-20230712-29-dtpug1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics like ketamine affect chemical messengers in the brain.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/abstract-brain-fractal-background-digital-illustration-2212346843">Shutterstock</a></span></figcaption></figure><p>Ketamine might be better known as a recreational drug or anaesthetic. But there’s growing evidence for its use for people with hard-to-treat depression.</p>
<p>An Australasian study <a href="https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/efficacy-and-safety-of-a-4week-course-of-repeated-subcutaneous-ketamine-injections-for-treatmentresistant-depression-kads-study-randomised-doubleblind-activecontrolled-trial/FDBAEC51F0891B57F5B04C572D13DA17">out today</a> showed some positive results for people with treatment-resistant depression when they had ketamine injections.</p>
<p>But we don’t know if these effects are sustained in the long term, and there are other ways of delivering ketamine. There are also other treatment options for this type of depression.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">Weekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression</a>
</strong>
</em>
</p>
<hr>
<h2>What is ketamine?</h2>
<p>Ketamine has been used as a powerful <a href="https://www.nature.com/articles/s41593-022-01203-5">general anaesthetic</a> for more than 50 years.</p>
<p>It’s also an <a href="https://www.ncbi.nlm.nih.gov/books/NBK470357/">illicit drug</a> of abuse and is considered a psychedelic. Psychedelics dramatically alter some neurotransmitters (chemical messengers) in the brain <a href="https://pubmed.ncbi.nlm.nih.gov/36280799/">to create</a> a profound change in perception, mood and anxiety.</p>
<p>In early animal studies, ketamine led to increase in levels of certain brain chemicals, such as dopamine, by <a href="https://www.nature.com/articles/mp2017190">up to 400%</a>. This led researchers to trial ketamine in humans to see what would happen in our brains.</p>
<p>Now, doses of ketamine (at those lower than used as an anaesthetic) are being used to help treatment-resistant depression. That’s when someone has tried at least two antidepressants and shows no improvement.</p>
<p>It is usually prescribed under strict conditions and observation that mitigate some <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322816/">serious risks</a>, such as increased feelings about suicide in some people. So people need to be assessed and monitored not only during treatment, but afterwards.</p>
<p>But some clinicians have resisted using ketamine due to its potential to become a <a href="https://www.ranzcp.org/getmedia/75baa529-2b71-419f-993a-2ff64ede50fe/cm-use-of-ketamine-in-psychiatric-practice.pdf">drug of abuse</a>.</p>
<p>Ketamine is also used to treat other mental health disorders such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959757/">PTSD</a> (post-traumatic stress disorder).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/hallucinations-in-the-movies-tend-to-be-about-chaos-violence-and-mental-distress-but-they-can-be-positive-too-204547">Hallucinations in the movies tend to be about chaos, violence and mental distress. But they can be positive too</a>
</strong>
</em>
</p>
<hr>
<h2>How about this new study?</h2>
<p>The research involved <a href="https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12616001096448">multiple centres</a> across Australia and New Zealand and compared how well ketamine injected <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">under the skin</a> compared with taking another drug in treating people with treatment-resistant depression.</p>
<p>The trial randomised the 184 study participants into different groups – some receiving ketamine, the rest the drug <a href="https://pubmed.ncbi.nlm.nih.gov/9258787/">midazolam</a>, twice a week over four weeks. Neither the study participants nor those assessing the results knew who had ketamine and who didn’t.</p>
<p>At the start of the study, all participants had a clinical depression score of at least 20 (moderate depression) using a particular scale known as the Montgomery-Asberg Depression Rating Scale.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Doctor in white coat putting hand on shoulder of patient" src="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The study participants had moderate depression.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-psychiatrist-shakes-hands-encouragement-patient-2188082723">Shutterstock</a></span>
</figcaption>
</figure>
<p>The researchers then looked for a score of less than 11, indicating a shift from a depression to remission.</p>
<p>After four weeks, there was a big difference between people treated with ketamine (19.6% in remission) compared with midazolam (2%). Another, less-strict way of measuring outcomes is to look for a halving of the depression score. This had an even bigger difference (29% compared with 4%). </p>
<p>However, four weeks after the treatment had ended, there was only limited sustained improvement in symptoms in the ketamine group. This suggests treatment may be needed over a longer period.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/do-psychedelics-really-work-to-treat-depression-and-ptsd-heres-what-the-evidence-says-208857">Do psychedelics really work to treat depression and PTSD? Here's what the evidence says</a>
</strong>
</em>
</p>
<hr>
<h2>There are other options</h2>
<p>In the trial, ketamine was given via an injection under the skin, which is a low-cost and efficient option. But ketamine can also be delivered directly into the bloodstream via an intravenous drip. Neither of these two options are routinely available in Australia and New Zealand outside clinical trials.</p>
<p>A third option uses a <a href="https://www.nps.org.au/australian-prescriber/articles/esketamine-hydrochloride-for-treatment-resistant-depression">different form</a> of ketamine and comes in a <a href="https://www.spravato.com/">nasal spray</a> (approved for use in <a href="https://www.tga.gov.au/resources/auspmd/spravato">Australia</a> and New Zealand). </p>
<p>Each option delivers ketamine in different amounts, and research into how these work in practice, and how they compare, is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">ongoing</a>.</p>
<p>There are also other drug and non-drug options for treatment-resistant depression. These include:</p>
<ul>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/33834408/">transcranial magnetic stimulation</a>, which stimulates parts of the brain to improve mood</p></li>
<li><p><a href="https://www.ranzcp.org/events-learning/psychedelic-assisted-therapy">psilocybin</a>, another psychedelic drug that has just been given the go-ahead for use in Australia under strict conditions as part of <a href="https://theconversation.com/psychedelic-medicine-is-on-its-way-but-its-not-doing-shrooms-with-your-shrink-heres-what-you-need-to-know-208568">psychedelic-assisted therapy</a></p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429332/">psychotherapy</a> (talking therapy) such as cognitive behavioural therapy, <a href="https://www.psychologytoday.com/au/therapy-types/acceptance-and-commitment-therapy">acceptance and commitment therapy</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/29761488/">dialectical behaviour therapy</a></p></li>
<li><p>changing some lifestyle factors, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164235/">such as diet</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/28110494/">exercise</a>, or <a href="https://pubmed.ncbi.nlm.nih.gov/32985916/">practising mindfulness</a> meditation.</p></li>
</ul>
<h2>In a nutshell</h2>
<p>Serious consequences of depression include <a href="https://theconversation.com/suicide-rates-are-rising-with-or-without-13-reasons-why-lets-use-it-as-a-chance-to-talk-116434">suicide</a> or a lifetime of anguish. This latest research shows promising outcomes for people whose symptoms are harder to treat. But this option is not yet widely available outside a clinical trial. Only the ketamine nasal spray has been approved for use in Australia and New Zealand.</p>
<p>There are also other treatments. So if your existing treatment is not working for you, discuss this with your doctor who will explain what else is available.</p>
<hr>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14. Beyond Blue provides the free resource <a href="https://www.beyondblue.org.au/docs/default-source/resources/bl0556-what-works-for-depression-booklet_acc.pdf?sfvrsn=fe1646eb_2">A guide to what works for depression</a>.</em></p><img src="https://counter.theconversation.com/content/209591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Musker does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>This latest research provides hope for people whose symptoms are harder to treat.Michael Musker, Enterprise Fellow (Senior Research Fellow/Senior Lecturer), University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2082242023-06-22T14:47:29Z2023-06-22T14:47:29ZAntidepressants can cause withdrawal symptoms – here’s what you need to know<figure><img src="https://images.theconversation.com/files/533503/original/file-20230622-29-r8rnfw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3994%2C2994&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Withdrawal symptoms will vary for each person.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/green-white-10-packet-pills-depression-666180598">callumrc/ Shutterstock</a></span></figcaption></figure><p>Millions of people worldwide take antidepressants to help with depression. But as a recent <a href="https://www.bbc.co.uk/programmes/p0fw1nm4">BBC Panorama</a> found, many aren’t aware of the fact that antidepressants can cause withdrawal symptoms when you stop taking them. For some, these symptoms can be severe and long-lasting. </p>
<p>Here’s what you should know.</p>
<h2>What causes antidepressant withdrawal?</h2>
<p>When we take psychotropic medications such as antidepressants, over time the brain and body <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">adapt to the drug</a>. This process of adaption is often termed <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">physical dependence</a>, which leads to tolerance (lessening effects over time) and withdrawal when stopping. Dependence is different from addiction, which also involves cravings and compulsive use. People do not become addicted to antidepressants. </p>
<p>Most modern antidepressants flood the brain with abnormally high levels of serotonin – a naturally occurring brain chemical that carries messages between nerve cells. Serotonin is involved in many body processes including learning, memory, sleep and sexual function. After even just a few weeks of antidepressant use, our serotonin receptors <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">become less sensitive</a>, meaning that we probably need more serotonin to elicit the same effects.</p>
<p>So, when the drug dose is reduced or stopped, the brain and body “miss” the drug. This is what causes withdrawal symptoms. </p>
<p>Withdrawal can also happen with <a href="https://academic.oup.com/braincomms/article/1/1/fcz025/5588408">other psychotropic drugs</a> such as benzodiazepines (used to treat insomnia and seizures), nicotine and caffeine.</p>
<h2>What are the symptoms?</h2>
<p>Since antidepressants affect multiple organ systems, there’s an array of potential withdrawal symptoms they can cause – both emotional and physical.</p>
<p><a href="https://www.thelancet.com/article/S2215-03661930032-X/fulltext">Emotional withdrawal symptoms</a> include low mood, anxiety, panic attacks, irritability, anger, crying spells and feeling suicidal. These can occur even in people who have never had these symptoms before – for example, those prescribed antidepressants <a href="https://www.liebertpub.com/doi/10.1089/jwh.2011.2764">to treat conditions</a>, such as menopause, that are unrelated to mental health problems.</p>
<p>As these symptoms overlap with those of anxiety and depression, they can <a href="https://www.cambridge.org/core/journals/bjpsych-advances/article/distinguishing-relapse-from-antidepressant-withdrawal-clinical-practice-and-antidepressant-discontinuation-studies/AE99BDE4435521CE9F3D626AE14D1962">easily be mistaken</a> as someone’s underlying mental health condition returning. This can lead people to being advised to continue taking the medication.</p>
<p>Physical withdrawal symptoms can include dizziness, light-headedness, a sensation that things are “not real” (depersonalisation/derealisation), muscle cramps, headaches, insomnia, trouble concentrating, nausea, and brain “zaps” (the feeling of electrical sensations shooting through the head). In severe cases, withdrawal can cause akathisia – defined as “restlessness”, this may feel as though the nervous system is “<a href="https://akathisiaalliance.org/?gclid=Cj0KCQjwnMWkBhDLARIsAHBOftppLw63U1cCi1EwentqsSb36KomAT2I1-A3mD4dIg-mOM5IBf4kWO4aAsPsEALw_wcB">on fire</a>”.</p>
<p>There are a few ways to <a href="https://www.cambridge.org/core/journals/bjpsych-advances/article/distinguishing-relapse-from-antidepressant-withdrawal-clinical-practice-and-antidepressant-discontinuation-studies/AE99BDE4435521CE9F3D626AE14D1962#comments">distinguish withdrawal symptoms from relapse</a> – the return of a past mental health condition. First, withdrawal symptoms often happen soon (typically days but sometimes weeks) after reducing your antidepressant dosage. Relapse tends to occur after a longer period. </p>
<p>Physical withdrawal symptoms will be distinct from the original condition, and sometimes the emotional symptoms are recognisably different from the symptoms you initially had. These physical and emotional symptoms generally resolve swiftly when you take antidepressants again.</p>
<h2>How long do withdrawal symptoms last?</h2>
<p>Many people (including practitioners) believe withdrawal symptoms only last as long as it takes the drug to leave your system – typically, days or weeks. </p>
<figure class="align-center ">
<img alt="A doctor holds a box of medication in their hand while writing on their clipboard. A patient sits across from them." src="https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=417&fit=crop&dpr=1 600w, https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=417&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=417&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=524&fit=crop&dpr=1 754w, https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=524&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/533504/original/file-20230622-17-b1mqei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=524&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Even practitioners may be unaware of how long withdrawal symptoms can last.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/these-best-antidepressants-on-market-cropped-2170157393">PeopleImages.com/Yuri A/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But symptoms are caused by a difference between the amount of drug your brain has become accustomed to, and the amount in your system. As such, they can last as long as it takes the <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">brain to become re-accustomed</a> to lower levels of the drug – possibly until the sensitivity of serotonin receptors has recovered. </p>
<p>Brain changes in response to antidepressants can <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">persist for years</a>. Clinical studies have also shown that antidepressant withdrawal symptoms can last for weeks, months and, in some people, <a href="https://journals.sagepub.com/doi/10.1177/2045125320980573?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%2520%25200pubmed">years</a>. A recent trial showed that in patients who stopped antidepressants after two years of use, withdrawal symptoms lasted an <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2106356">average of nine months</a>.</p>
<h2>Does withdrawal only happen with long-term use?</h2>
<p>The longer you take an antidepressant, the more likely you are to experience withdrawal effects – and the more likely they are to be severe. </p>
<p><a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">One patient survey</a> found only a small minority experienced withdrawal after taking the drug for a few months. But more than half who’d taken antidepressants longer than three years experienced withdrawal – of which, half reported moderate or severe symptoms.</p>
<p>However, withdrawal symptoms have also been observed in people taking antidepressants for only <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">4-6 weeks</a> – and more rarely, after only days of use.</p>
<h2>How should you stop antidepressants?</h2>
<p>For a long time, guidelines have suggested that antidepressants can be stopped in four weeks. The most common approach doctors use is halving the dose for two weeks, then halving the dose again (often by taking a tablet every second day) for two weeks, before stopping. </p>
<p>While some patients can tolerate this, we know that for many long-term antidepressant users, this approach produces intolerable withdrawal symptoms that can make it <a href="https://www.sciencedirect.com/science/article/pii/S0022395623001309?via%3Dihub">impossible to stop these drugs</a>.</p>
<p>More recent guidance from the <a href="https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stopping-antidepressants">Royal College of Psychiatrists</a> and <a href="https://www.nice.org.uk/guidance/ng222">National Institute for Health and Care Excellence</a> (Nice) recommends that people who experience withdrawal should taper off more gradually over months – and for some, years. This should be adjusted depending on the person and their symptoms.</p>
<p>The latest guidance also advises using “<a href="https://www.thelancet.com/article/S2215-03661930032-X/fulltext">hyperbolic tapering</a>”, in which reductions are made by small increments. The last few milligrams of these drugs are the hardest to come off, so need to be reduced particularly carefully. To do this, patients would need very small doses of medications – much smaller than most available tablets, which is why liquid versions are recommended by Nice. </p>
<p>There are many reasons why a person may choose to start antidepressants. But it’s important people are made aware of the risk of withdrawal effects, so they can make an <a href="https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19---antidepressants-and-depression.pdf?sfvrsn=ddea9473_">informed decision</a>.</p><img src="https://counter.theconversation.com/content/208224/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Horowitz is a collaborating investigator on the RELEASE trial in Australia investigating supported, gradual, hyperbolic tapering of antidepressants. He is a member of the Critical Psychiatry Network and an associate of the International Institute for Psychiatric Drug Withdrawal (IIPDW). He is a co-founder of Outro Health, which helps people who wish to stop unnecessary antidepressant medication in North America using gradual, hyperbolic tapering.</span></em></p>The longer you taken an antidepressant, the more likely you are to experience withdrawal effects.Mark Horowitz, Honorary Clinical Research Fellow in Psychiatry, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2019372023-04-17T12:42:31Z2023-04-17T12:42:31ZPsychedelics may better treat depression and anxiety symptoms than prescription antidepressants for patients with advanced cancer<figure><img src="https://images.theconversation.com/files/521074/original/file-20230414-28-z0dpc7.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psilocybin and other psychedelics could help patients process the challenges of a cancer diagnosis.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/magic-mushrooms-illustration-royalty-free-illustration/1390280399">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>In people with advanced cancer, psychedelic drugs like psilocybin, LSD and MDMA may significantly <a href="https://doi.org/10.1097/coc.0000000000000998">reduce the severity of depression and anxiety</a> symptoms.</p>
<p>Roughly 10% of <a href="https://doi.org/10.1016/S1470-2045(11)70002-X">patients with cancer</a> experience anxiety, while 20% report depression. However, current research suggests that available prescription antidepressants <a href="https://doi.org/10.1002%2F14651858.CD011006.pub2">do not significantly decrease depressive symptoms</a> in cancer patients compared with a placebo. </p>
<p><a href="https://scholar.google.com/citations?user=lWAD9d8AAAAJ&hl=en">My team and I</a> recently completed a <a href="https://doi.org/10.1097/coc.0000000000000998">meta-analysis of five clinical trials</a> examining anxiety and depression symptoms in patients with advanced forms of cancer and other life-threatening diseases. We found that taking psychedelic medication alone – specifically LSD, psilocybin or MDMA – reduced depression scores as measured by the <a href="https://instruct.uwo.ca/kinesiology/9641/Assessments/Psychological/BDI.html">Beck’s Depression Inventory</a> by six points, where a score below 10 indicates minimal to no depression and above 30 indicates major depression. The average scores at baseline were between 15 and 18 for most studies, though one trial had a baseline of <a href="https://doi.org/10.1038/s41598-020-75706-1">approximately 30</a>. Psychedelics also reduced anxiety scores as measured by the <a href="https://doi.org/10.1159/000478993">State-Trait Anxiety Inventory</a> by seven to eight points, where a score of 20 to 37 indicates no or minimal anxiety and a score of 45 to 80 indicates high anxiety. The average scores were between 40 and 55 but <a href="https://doi.org/10.1038/s41598-020-75706-1">approximately 60 in one trial</a>.</p>
<p>In one trial of 51 cancer patients, 60% of those who received a single high-dose psilocybin session <a href="https://doi.org/10.1177/0269881116675513">achieved clinical remission</a> for depression, and 52% did for anxiety. In comparison, 16% of those who received a placebo achieved remission for depression and 12% for anxiety. These effects were still maintained six months later.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/b5i0aY_rUZU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Researchers are studying the use of psychedelics to treat a number of mental health conditions.</span></figcaption>
</figure>
<h2>Psychedelics and trauma</h2>
<p>Why would one to two psychedelic therapy sessions be more effective than taking daily prescription medications like fluoxetine (Prozac) and paroxetine (Paxil)?</p>
<p>Receiving a cancer diagnosis and experiencing adverse effects from treatments can be traumatic. In severe cases, patients can develop <a href="https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq">cancer-related post-traumatic stress disorder</a>. </p>
<p>People who develop PTSD from military service or physical or sexual violence <a href="https://doi.org/10.1002%2Fda.22881">commonly experience depression and anxiety</a>. Research on <a href="https://doi.org/10.1002/jcph.1995">MDMA-facilitated psychotherapy</a>, in which psychotherapists incorporate psychedelic sessions with traditional counseling, has shown that this treatment approach can effectively reduce PTSD symptoms by allowing patients to be willing and able to share traumatic memories to help process them. These reductions were larger than those seen in studies on prescription antidepressants alone.</p>
<p>Based on this research, my team and I hypothesize that psychedelic sessions might have an advantage over traditional prescription antidepressants for patients with cancer-related depression or anxiety because it may help them deal with their underlying trauma. </p>
<p>Some of the trials in our review noted what patients perceived as the <a href="https://doi.org/10.1177/10600280221144055">reasons for the reduced anxiety and depression symptoms</a> they experienced. Patients stated that the psychedelic sessions helped them process the intense feelings they were repressing without being overwhelmed. While the catharsis was emotional and difficult, it helped them achieve acceptance of those emotions, lessening their feelings of isolation and inner withdrawal.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Patient in hospital gown with IV sitting on bed, looking out window" src="https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/521093/original/file-20230414-24-x6w4qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cancer can be a traumatic experience.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/patient-woman-in-hospital-room-royalty-free-image/1468190611">aquaArts studio/E+ via Getty Images</a></span>
</figcaption>
</figure>
<h2>Unknowns in psychedelic therapy</h2>
<p>While these results are promising, there are limitations to the available research that could bias the results. A <a href="https://doi.org/10.1097/coc.0000000000000998">number of the advanced cancer studies</a> we examined included people with a history of psychedelic use. People with prior positive recreational psychedelic experiences may be more likely to participate in these studies than those who experienced a “bad trip” or were opposed to recreational drugs altogether. Additionally, even though the placebo was made to look identical, it is unlikely that patients or caregivers were fooled if it did not elicit a psychedelic effect.</p>
<p>While past studies have found lackluster benefits from traditional antidepressant medications compared with placebos <a href="https://doi.org/10.1002/jcph.1995">in PTSD</a> and <a href="https://doi.org/10.1002%2F14651858.CD011006.pub3">cancer-induced anxiety and depression</a>, there have not been any clinical trials directly comparing the effectiveness of traditional antidepressants with psychedelics for PTSD or cancer patients. However, one completed early-phase trial that compared psilocybin with the traditional antidepressant escitalopram (Lexapro) in <a href="https://doi.org/10.1056/NEJMoa2032994">patients with major depression</a> found that 57% of people receiving psilocybin achieved clinical remission, compared with only 28% receiving escitalopram.</p>
<p>Finally, psychedelic sessions caused large <a href="https://doi.org/10.1097/coc.0000000000000998">increases in blood pressure</a>. This might not be the best treatment for patients with poorly controlled hypertension or with heart disease. </p>
<h2>Next steps for psychedelics</h2>
<p>More research is needed on effectiveness of psychedelics to treat anxiety and depression in cancer patients. Exploring psychedelic treatments for patients with other life-threatening diseases that cause trauma, anxiety or depression could clarify their potential therapeutic benefits.</p>
<p>Were the Food and Drug Administration to approve psychedelics for this kind of use, the agency would need to figure out how these psychedelics can be used legally. As <a href="https://www.ecfr.gov/current/title-21/chapter-II/part-1308#p-1308.11(d)">Schedule 1 drugs</a>, they are currently banned from any medical use in the U.S. Researchers must <a href="https://www.deadiversion.usdoj.gov/GDP/(DEA-DC-057)(EO-DEA217)_Researchers_Manual_Final_signed.pdf">register with the U.S. Drug Enforcement Agency</a> to study controlled substances. However, the FDA has already set a precedent with its June 2018 approval of <a href="https://doi.org/10.1002/jcph.1387">cannabadiol (Epidiolex)</a> for the treatment of rare childhood seizure disorders, even though this cannabis derivative remains banned by the Drug Enforcement Administration.</p><img src="https://counter.theconversation.com/content/201937/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>C. Michael White does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Receiving a cancer diagnosis and undergoing cancer treatment can be a traumatizing experience. Psychedelics like LSD, psilocybin and MDMA could help alleviate symptoms from cancer-related PTSD.C. Michael White, Professor of Pharmacy Practice, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2012822023-04-13T12:26:33Z2023-04-13T12:26:33ZRare and tragic cases of postpartum psychosis are bringing renewed attention to its risks and the need for greater awareness of psychosis after childbirth<figure><img src="https://images.theconversation.com/files/520054/original/file-20230410-21-8gu2ze.jpg?ixlib=rb-1.1.0&rect=46%2C38%2C5071%2C3337&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Postpartum depression affects approximately 1 in 8 mothers in the U.S. Postpartum psychosis is far more rare, occurring in about 1 in every 500 deliveries.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/post-natal-depression-royalty-free-image/523523660?phrase=postpartum%20depression&adppopup=true">Justin Paget/Stone via Getty Images</a></span></figcaption></figure><p>Lindsay Clancy, a labor and delivery nurse at the prestigious Massachusetts General Hospital in Boston, is the latest tragic and high-profile example of a mother allegedly taking the lives of her own three children. </p>
<p>On Jan. 24, 2023, Clancy allegedly strangled the children with an exercise band <a href="https://www.cbsnews.com/boston/news/duxbury-mother-lindsay-clancy-murder-charges-arraignment/">while her husband ran an errand</a>. Clancy then slit her wrists, cut her neck and jumped from the second floor of their home. She has been hospitalized since, <a href="https://original.newsbreak.com/@lavinia-thompson-1593703/2947272675961-lindsay-clancy-remains-in-hospital-after-allegedly-killing-kids-talks-open-up-about-postpartum-psychosis">apparently paralyzed from the waist down</a> following her suicide attempt.</p>
<p>At her arraignment, Clancy’s defense lawyer stated that she may have been suffering from <a href="https://www.usatoday.com/story/life/health-wellness/2023/02/15/lindsay-clancy-duxbury-postpartum-psychosis-explained/11247303002/">an extreme form of postpartum depression</a> called postpartum psychosis. Other women have made this claim, including Andrea Yates, a Texas woman who in 2001 <a href="https://engagedscholarship.csuohio.edu/cgi/viewcontent.cgi?article=1174&context=clevstlrev">drowned her five children in a bathtub</a>. She was convicted of capital murder at her first trial, but after a successful appeal, she was found not guilty by <a href="http://edition.cnn.com/TRANSCRIPTS/0607/26/ng.01.html">reason of insanity in her second trial</a>.</p>
<p>The Centers for Disease Control and Prevention estimate that 1 in 8 mothers, or approximately 12%, <a href="https://www.cdc.gov/reproductivehealth/features/maternal-depression/index.html">experience postpartum depression</a>. Cases of parents killing children, in contrast, are exceedingly rare, with estimates of <a href="https://doi.org/10.4103%2F0019-5545.196845">about 500 of these tragic events per year</a> in the U.S. </p>
<p>Many people wonder whether a psychiatric condition, no matter how severe, could justify or explain the killing of innocent children, especially by their own mother.</p>
<p>As a <a href="https://scholar.google.com/citations?user=lrkXDDAAAAAJ&hl=en">clinical and forensic psychiatrist</a>, I routinely treat patients after delivery for depression, and I have evaluated women accused of killing their children. The potentially fatal outcomes make it imperative to increase awareness and understanding of postpartum depression and psychosis.</p>
<h2>Postpartum depression explained</h2>
<p>It is important to make a distinction between “postpartum blues” and postpartum depression. Research shows that between 15% to 85% of women have “postpartum blues,” and the <a href="https://doi.org/10.1016/j.ajog.2008.11.033">incidence peaks around the fifth day following delivery</a>. Postpartum blues can include low mood, tearfulness, irritability and feeling overwhelmed. It is a totally normal, transient condition thought to be a result of the rapid drop in hormone levels following delivery.</p>
<p>True <a href="https://www.psychiatry.org/patients-families/peripartum-depression/what-is-peripartum-depression">postpartum depression</a> is more severe than postpartum blues. This term refers to when the patient is experiencing symptoms of a <a href="https://theconversation.com/when-does-clinical-depression-become-an-emergency-4-questions-answered-200231">clinical depressive episode</a>, also called “major depressive episode,” <a href="https://www.acog.org/womens-health/faqs/postpartum-depression">usually within the first month after delivery</a>. </p>
<p><a href="https://www.psychiatry.org/patients-families/depression/what-is-depression">Postpartum depression is defined as</a> experiencing two weeks or more of some or all of the following symptoms: depressed mood for most of the day, diminished interest or pleasure in most activities, weight loss, inability to sleep or excessive sleep, physical slowing or agitation, fatigue, poor concentration and, in severe cases, suicidal thoughts. The medical community estimates that postpartum depression is very common, <a href="https://doi.org/10.3949/ccjm.87a.19054">with rates of 10% to 20%</a> in the U.S., and the true numbers may be higher.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/6kaCdrvNGZw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Baby blues are characterized by worries such as “Am I a good mom?” that typically pass within a few weeks after childbirth, whereas postpartum depression involves longer-lasting feelings of disconnectedness.</span></figcaption>
</figure>
<p>The onset and duration of postpartum depression can <a href="https://my.clevelandclinic.org/health/diseases/9312-postpartum-depression">vary greatly</a>. For some patients, the first weeks and months after delivery may go well or mood symptoms may be manageable, followed months later by a “crash.” For others, mood symptoms may begin during pregnancy and <a href="https://theconversation.com/more-than-4-in-5-pregnancy-related-deaths-are-preventable-in-the-us-and-mental-health-is-the-leading-cause-193909">worsen after delivery</a>. </p>
<p>Diagnosis can be difficult since the time of onset is variable and because some of the symptoms of depression are normal, temporary changes that occur after delivery. In addition, research shows that <a href="https://doi.org/10.1016/j.jad.2005.12.051">cultural factors can influence</a> the reporting and development of postpartum depression, and some patients may not disclose symptoms due to guilt or shame.</p>
<h2>Risk factors for postpartum depression</h2>
<p>Some key <a href="https://doi.org/10.1016/j.genhosppsych.2004.02.006">risk factors for postpartum depression</a> include a history of depression or mental illness prior to pregnancy, stressful life events during and after pregnancy, marital conflict and young maternal age.</p>
<p>New mothers are under a great deal of pressure – personal, familial and societal – to immediately bond with and love their children. The stress and burden of being a new parent, and the tasks that go along with this role, such as breastfeeding, often make bonding with the child a challenge. The patient may struggle with feelings of guilt and shame, which can delay or prevent seeking help.</p>
<p>While the physical causes of postpartum depression remain mysterious, researchers believe the condition is caused by <a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.157.6.924">hormone fluctuations during and especially after pregnancy</a>. For example, research suggests that sex hormones like estrogen, which reach high levels during pregnancy and then fall precipitously after delivery, as well as hormones like oxytocin that are <a href="https://doi.org/10.1017/s1092852900010312">involved in lactation and maternal-baby bonding</a>, likely play an important role. During and after pregnancy, the brain is on a hormonal roller coaster, and this can wreak havoc on mental health.</p>
<h2>Postpartum depression treatments</h2>
<p>For mild cases, psychotherapy alone may be sufficient to reduce the symptoms and gradually restore a sense of well-being. Approaches such as <a href="https://doi.org/10.1016/j.jad.2018.10.361">interpersonal psychotherapy</a> and <a href="https://doi.org/10.1002/14651858.CD006116.pub2">cognitive behavioral therapy</a> have been shown to be helpful for those suffering with postpartum depression. Interpersonal psychotherapy, for example, focuses on improving interpersonal connections, while cognitive behavioral therapy focuses on correcting distorted thinking, such as believing that one is a “bad” parent. </p>
<p>The mainstay of treatment for postpartum depression is medication. Given the probably strong biological underpinnings of this condition, medication is thought to be helpful in restoring <a href="https://doi.org/10.1186/s12991-018-0188-0">neurochemistry to alleviate symptoms</a>, such as by raising brain levels of the neurotransmitter serotonin.</p>
<p>Breastfeeding patients may prefer psychological treatment to medication therapy since <a href="https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/maternal-or-infant-illnesses/postpartum-depression.html#">antidepressants can enter breast milk</a>. To date, however, <a href="https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/maternal-or-infant-illnesses/postpartum-depression.html">antidepressants do not appear</a> to have an affect on the infant’s <a href="https://womensmentalhealth.org/specialty-clinics-2/breastfeeding-and-psychiatric-medication-2/">health or development</a>.</p>
<h1>How postpartum psychosis differs</h1>
<p>Postpartum psychosis is a condition where maternal mental health is affected not just by depression, but by <a href="https://www.nimh.nih.gov/health/publications/understanding-psychosis">a break with reality</a>. </p>
<p>The break with reality, called “psychosis,” generally includes seeing or hearing things that don’t exist – called hallucinations – having jumbled or disconnected thoughts or having fixed false beliefs, often of a bizarre or extremely implausible nature, such as the devil having entered into one’s child. For example, in the Andrea Yates case, she professed to believing that she was marked by Satan and that the only way to <a href="https://doi.org/10.1016/S0140-6736(06)69789-4">save her children from hell was by killing them</a>. Some patients may hear an auditory hallucination - meaning a powerful voice - commanding suicide or an attack on the infant.</p>
<p>This condition is much less common than postpartum depression and is thought to occur in <a href="https://my.clevelandclinic.org/health/diseases/24152-postpartum-psychosis">1 in 500, or 0.2%, of deliveries</a> in the U.S. Also, unlike postpartum depression, which can begin months after delivery, postpartum psychosis usually begins <a href="https://doi.org/10.1007/s00737-007-0174-z">within the first three days</a> following childbirth.</p>
<p>Due to the severe nature of these symptoms, their rapid onset and the frequent presence of thoughts of harming oneself or the baby, postpartum psychosis is considered a psychiatric emergency. It usually results in <a href="https://doi.org/10.3949/ccjm.87a.19054">psychiatric hospitalization</a> for the patient’s and the baby’s safety. In many cases, postpartum depression and its extreme form, postpartum psychosis, go undetected by loved ones and health care providers because of a reluctance to acknowledge that the patient may be a danger to oneself or the child. </p>
<h2>What experts know about Clancy’s Case</h2>
<p>Lindsay Clancy reportedly <a href="https://www.boston.com/news/crime/2023/02/21/lindsay-clancy-timeline-duxbury-mother-mental-health-treatment/">suffered from anxiety</a> about going back to work in September 2022, four to five months after giving birth to her third child. She was diagnosed with anxiety and prescribed anti-anxiety medications and antidepressants. </p>
<p>In December 2022, Clancy was evaluated at a women’s psychiatric clinic, where she was told she did not have postpartum depression. However, a short time later she told her husband she was having thoughts of harming herself and the children, and was admitted to a psychiatric hospital. She was discharged after a few days and reported that her suicidal thoughts had resolved. However, just a few days later, she allegedly strangled her three children.</p>
<p>If accurate, this timeline indicates how difficult it can be to diagnose possible postpartum depression and psychosis, and that symptoms may fluctuate on a daily or even hourly basis. Mothers may not always disclose symptoms due to guilt, shame or fear about how it could impact their family.</p>
<p>Clancy’s tragic story illustrates how important close mental health follow-up and treatment is for women suspected of having postpartum depression. And when suicidal thoughts or thoughts of harming the children are present, they must be treated as a potential psychiatric emergency.</p><img src="https://counter.theconversation.com/content/201282/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ziv E. Cohen does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Postpartum depression can strike days, weeks or months after delivery, and the much rarer cases of psychosis can be difficult to detect.Ziv E. Cohen, Clinical Assistant Professor of Psychiatry, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2011012023-03-15T16:56:45Z2023-03-15T16:56:45ZAntidepressant withdrawal should be taken seriously – we’re investigating ways to help people come off the pills<p>Misinformation about antidepressants <a href="https://www.psychologytoday.com/us/blog/side-effects/202004/antidepressants-and-online-misinformation">is rife</a> and is probably fuelling their rise in use. Chief among these false ideas are: </p>
<ul>
<li><p>Antidepressant withdrawal effects are mild and only last two to three weeks, with any severe symptoms interpreted as a relapse in depression. </p></li>
<li><p>Antidepressants are not addictive, so they can’t be that difficult to stop. </p></li>
<li><p>If you are having difficulty getting off your antidepressant, that shows you must need them. </p></li>
<li><p>You should be able to stop your antidepressants in a month or two.</p></li>
<li><p>Antidepressants work by growing new brain cells. </p></li>
</ul>
<p>It is now established that antidepressants produce withdrawal symptoms that often last for many <a href="https://www.nice.org.uk/guidance/ng222/chapter/Recommendations">weeks, months</a> or even <a href="https://journals.sagepub.com/doi/full/10.1177/2045125320980573">years</a>. </p>
<p>Claims that these symptoms only last for two to three weeks came from studies conducted by drug companies where people had only used antidepressants for a couple of <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">months</a>. A recent large <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2106356">study</a> found that people who have been on antidepressants for years reported having withdrawal symptoms lasting for nine months on average. </p>
<p>About half of the people who stop taking antidepressants experience <a href="https://www.sciencedirect.com/science/article/pii/S0306460318308347?via%3Dihub">withdrawal</a>. In surveys, half of the people who stop using these drugs report having severe withdrawal <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">symptoms</a>. </p>
<p>For some people, withdrawal symptoms are debilitating and prolonged. Symptoms <a href="https://journals.sagepub.com/doi/full/10.1177/2045125320967183?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org">include</a> dizziness, headache, problems with memory and concentration, emotional disturbance and neurological symptoms such as sensitivity to noise and light, muscle spasms and <a href="https://www.bmj.com/content/368/bmj.m754.long">sexual dysfunction</a>, all of which can persist for years after <a href="https://journals.sagepub.com/doi/full/10.1177/2045125320980573">stopping</a>. </p>
<p>The longer the drugs are taken, the more severe (and probably long-lasting) the withdrawal <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">effects</a>. </p>
<p>Withdrawal effects occur from antidepressants because the brain adapts to their presence. This is often called physical <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">dependence</a>. Dependence occurs even though antidepressants do not make people high or cause craving and compulsion, which is the technical <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2010.03144.x">definition</a> of “addiction”. </p>
<p>When antidepressants are stopped, the brain “misses” the drug and expresses this as withdrawal symptoms. These symptoms can last months or <a href="https://link.springer.com/article/10.1007/s40263-022-00960-y">years</a> because that is how long it can take for the brain to adjust to being without the drug. </p>
<p>Since withdrawal can cause emotional <a href="https://www.cambridge.org/core/journals/bjpsych-advances/article/distinguishing-relapse-from-antidepressant-withdrawal-clinical-practice-and-antidepressant-discontinuation-studies/AE99BDE4435521CE9F3D626AE14D1962">symptoms</a> such as anxiety, low mood, crying spells and panic attacks, people often misinterpret these symptoms as a return of their mental health problem - that is, a relapse. Doctors, too, are often unaware of how common and severe withdrawal symptoms can be, and often mistake them for a <a href="https://www.cambridge.org/core/journals/bjpsych-advances/article/distinguishing-relapse-from-antidepressant-withdrawal-clinical-practice-and-antidepressant-discontinuation-studies/AE99BDE4435521CE9F3D626AE14D1962">relapse</a>.</p>
<p>This can lead people who started antidepressants following a specific stressful event, like job loss, divorce or physical illness, to conclude that they have a long-term, relapsing illness when they do not. </p>
<p>There has also been a shift in understanding about how these drugs work. Many experts now agree that antidepressants do not work by correcting an underlying chemical <a href="https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672">imbalance</a>. Some people suggest that antidepressants work by growing new brain <a href="https://theconversation.com/considering-going-off-antidepressants-heres-what-to-think-about-first-198880">cells</a> but these claims are based on animal studies and this has never been shown in humans. </p>
<figure class="align-center ">
<img alt="The prescriptions counter at a pharmacy." src="https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/515274/original/file-20230314-18-cmek1c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The number of antidepressant items prescribed over the past six years in the UK has increased by 35%.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/london-june-2-2014-prescriptions-counter-1724981035">Alex Segre/Shutterstock</a></span>
</figcaption>
</figure>
<p>There is also no clear evidence that the growth of new brain cells is desirable. Indeed, it could reflect a negative effect, as damage to the brain also causes the growth of new <a href="https://www.sciencedirect.com/science/article/abs/pii/S0014488615001314">neurons</a> (as damage to the skin leads to the growth of new skin cells). </p>
<p>There are other explanations for how antidepressants exert their effects that are more plausible and supported by evidence. Antidepressants subtly change normal mental states, producing emotional numbing among other <a href="https://www.eurekaselect.com/article/90929">effects</a>. This has been shown in healthy <a href="https://theconversation.com/ssris-emotional-blunting-may-be-part-of-the-process-new-research-198264">volunteers</a>, confirming that emotional numbing is an effect of the drug and not just the depression. </p>
<p>This effect and other mental changes may account for the effect of antidepressants by suppressing the intensity of negative emotions. Or these effects may cue people to know they are taking a drug, which can amplify the placebo effect.</p>
<h2>Guidelines are finally catching up</h2>
<p>Advice from the UK’s <a href="https://www.nice.org.uk/guidance/ng222/chapter/Recommendations#delivery-of-treatments">National Institute for Health and Care Excellence</a> (Nice) and the Royal College of <a href="https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stopping-antidepressants">Psychiatrists</a> on how to safely stop antidepressants has changed markedly recently. Guidelines now recommend that after long-term use, antidepressants should be reduced in slow stages (tapering) over months and sometimes years down to very low doses. </p>
<p>As these doses are much smaller than can be made with widely available tablets, the guidelines call for the use of liquid versions of <a href="https://www.nice.org.uk/guidance/ng222/chapter/Recommendations#delivery-of-treatments">drugs</a> (specially made up smaller dose tablets are another option). </p>
<p>The approach to tapering recommended by these updated guidelines is called “hyperbolic <a href="https://www.thelancet.com/article/S2215-0366(19)30032-X/fulltext">tapering</a>”. It is based on the fact that very small doses of antidepressants have very large effects on the brain. This is often why the last few milligrams of a drug are the hardest to get <a href="https://journals.sagepub.com/doi/full/10.1177/2045125321991274">off</a>. </p>
<p>To account for the larger effects on the brain at lower drug doses, dose reductions have to be made in smaller and smaller amounts as you get down to lower doses – so that people make reductions of as little as 10% or 25% of their most recent dose. Studies show that this technique can help people who were previously not able to stop their medication with traditional approaches to <a href="https://journals.sagepub.com/doi/full/10.1177/20451253211039327">safely stop it</a>. We are currently testing this approach (hyperbolic tapering) in a large trial in <a href="https://medical-school.uq.edu.au/release">Australia</a>. </p>
<p>Unfortunately, other countries including <a href="https://www.ranzcp.org/files/resources/college_statements/clinician/cpg/mood-disorders-cpg-2020.aspx">Australia</a> and the <a href="http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf">US</a> have not updated their guidance and still recommend stopping antidepressants relatively rapidly. This can result in people experiencing severe withdrawal symptoms and falsely concluding that they cannot come off their medication. </p>
<p>The difficulty many experience in trying to stop antidepressants highlights the need to be much more careful in the prescribing of these drugs. The Nice guidelines <a href="https://www.nice.org.uk/guidance/ng222/chapter/Recommendations">recommend</a> that antidepressants should not be offered as a first-choice treatment in mild depression. Even in severe depression the guidelines now recommend eight non-drug alternatives, including problem-solving therapy, exercise and a <a href="https://www.nice.org.uk/guidance/ng222/resources/discussing-firstline-treatments-for-more-severe-depression-pdf-11131007007">variety of other therapies</a>. </p>
<p>This approach was also recently supported by NHS England in its <a href="https://www.england.nhs.uk/long-read/optimising-personalised-care-for-adults-prescribed-medicines-associated-with-dependence-or-withdrawal-symptoms/">announcement</a> of an initiative to move away from the “pill for every ill” approach, to fund non-pharmaceutical alternatives for mental health problems, and to provide long-awaited services to help people stop antidepressants.</p><img src="https://counter.theconversation.com/content/201101/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Horowitz is a Collaborating Investigator on the RELEASE trial in Australia investigating supported, gradual, hyperbolic tapering of antidepressants. He is member of the Critical Psychiatry Network and an Associate of the International Institute for Psychiatric Drug Withdrawal (IIPDW). He is a co-founder of Outro Health which helps people who wish to stop unnecessary antidepressant medication in Canada and the US using gradual, hyperbolic tapering.</span></em></p><p class="fine-print"><em><span>Joanna Moncrieff is a co-investigator on a National Institute of Health Research funded study exploring methods of antidepressant discontinuation. She is co-chair person of the Critical Psychiatry Network, an informal and unfunded group of psychiatrists and an unpaid board member of the voluntary group, the Council for Evidence-based Psychiatry.</span></em></p><p class="fine-print"><em><span>Katharine Wallis receives funding from the Commonwealth Department of Health, Medical Research Future Fund, Clinician Researchers Applied Research in Health - MRFAR000079</span></em></p>Antidepressants have been prescribed to millions of people with little thought about how those people will come off them.Mark Horowitz, Clinical Research Fellow in Psychiatry, UCLJoanna Moncrieff, Professor of Critical and Social Psychiatry, UCLKatharine Wallis, Professor, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1982822023-03-15T12:21:41Z2023-03-15T12:21:41ZDepression too often gets deemed ‘hard to treat’ when medication falls short<figure><img src="https://images.theconversation.com/files/514748/original/file-20230310-29-jqe5vl.jpg?ixlib=rb-1.1.0&rect=0%2C45%2C5106%2C3332&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A diagnosis of treatment-resistant depression can lead to a sense of hopelessness and despair in some patients.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/worried-young-woman-sitting-on-bed-at-home-royalty-free-image/1393174810">Maria Korneeva/Moment via Getty Images</a></span></figcaption></figure><p>A plumber who shows up to fix a leaking toilet with a single tool is not likely to succeed. The same is true if a mental health professional offers only one approach for a complex problem like depression.</p>
<p>Sadly, the number of people <a href="https://www.who.int/news-room/fact-sheets/detail/depression">struggling with depression</a> <a href="https://www.who.int/news/item/02-03-2022-covid-19-pandemic-triggers-25-increase-in-prevalence-of-anxiety-and-depression-worldwide">increased dramatically</a> at the height of the COVID-19 pandemic. <a href="https://doi.org/10.1016/j.jad.2023.01.050">Stress</a> – from school closures to job losses to the death of loved ones – made life more challenging and increased the risk of developing emotional difficulties. For some groups that have experienced discrimination, <a href="https://doi.org/10.1007/s40615-022-01284-9">ongoing inequities</a> made their mental health even worse. </p>
<p>There is a professional debate about <a href="https://doi.org/10.1353/pbm.0.0009">whether depression is a social problem</a> <a href="https://www.psychiatry.org/patients-families/depression/what-is-depression">or a disease</a>. Despite this debate, a 62% increase in <a href="https://www.finance.senate.gov/imo/media/doc/SFC%20Mental%20Health%20Report%20March%202022.pdf">yearly spending on U.S. mental health care</a>, from US$131 billion in 2006 to $212 billion in 2015, has not led to the intended level of improvement for patients. </p>
<p>This makes it clear that the <a href="https://www.hsph.harvard.edu/ecpe/why-leadership-in-mental-health-care-is-needed-now-more-than-ever-and-how-to-implement-change/">current approach is falling short</a>, but there are a host of viable alternatives for helping to treat patients who are suffering with depression.</p>
<p>We are a <a href="https://scholar.google.com/citations?hl=en&user=LFOKsvwAAAAJ&view_op=list_works&sortby=pubdate">health and biological psychologist</a> who treats hospitalized patients with depression and anxiety and a <a href="https://scholar.google.com/citations?user=p3SsTKUAAAAJ&hl=en&oi=ao">doctoral student in social work</a> studying how to improve the lives of socially isolated older adults.</p>
<p>As mental health professionals, we see the effects of the <a href="https://www.psychiatrictimes.com/view/mental-health-america-crisis">ongoing mental health crisis</a> on a daily basis. </p>
<h2>An overreliance on medication causes harm</h2>
<p>More than <a href="https://pubmed.ncbi.nlm.nih.gov/33054926/">13% of U.S. adults take an antidepressant medication</a> for depression or for other reasons. <a href="https://doi.org/10.3389/fpsyt.2019.00407">Many people report feeling better</a> on antidepressants, though there is <a href="https://theconversation.com/in-research-studies-and-in-real-life-placebos-have-a-powerful-healing-effect-on-the-body-and-mind-173845">debate about what causes the improvements</a>. </p>
<p>Unfortunately, nearly 3 in 4 who take these drugs <a href="https://psycnet.apa.org/doi/10.1037/cns0000261">do not get complete relief from antidepressants</a>. As we discussed in a recent paper, people who do not feel better on antidepressants are usually categorized as having a <a href="https://doi.org/10.1016/j.ssmmh.2022.100081">difficult-to-treat type of depression</a> referred to, controversially, as “treatment-resistant depression.” </p>
<p>We see patients <a href="https://doi.org/10.1016/j.psc.2011.11.004">who feel demoralized</a> by the implied and untrue notion that their depression is “incurable” after only trying medication but not <a href="https://doi.org/10.1176/appi.ajp.2021.21050535">lower-risk treatments</a> like psychotherapy and <a href="https://doi.org/10.1016/S2215-0366(20)30036-5">other effective alternatives</a>. We help them find hope again.</p>
<p>The U.S. health care system <a href="https://www.usnews.com/news/health-news/articles/2022-04-20/in-long-run-antidepressants-dont-improve-quality-of-life-study">relies heavily on medication</a> and other <a href="https://pubmed.ncbi.nlm.nih.gov/31612847/">biomedical treatments</a> for depression. But in fact there are numerous non-drug-based solutions for prevention and treatment of depression. </p>
<p>Holistic concepts that promote <a href="https://doi.org/10.1016/j.ssmmh.2021.100052">flourishing</a> and <a href="https://doi.org/10.1027/1016-9040/a000294">thriving</a>, as well as <a href="https://www.va.gov/wholehealth/">whole-health initiatives</a> and <a href="https://doi.org/10.1056%2FNEJMp1917461">mind-body medicine</a> focus on the entire person. These concepts have not yet been fully integrated into approaches to public mental health. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/MAvSs2u-7eU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The word ‘heal’ is derived from the same Latin and Greek words that mean ‘whole.’</span></figcaption>
</figure>
<h2>The quest to understand well-being and depression</h2>
<p>There are many hardworking, highly successful people who do not feel fulfilled with life from time to time. When this internal lack of fulfillment also includes other symptoms like a loss of hope and becomes severe enough to disrupt daily life for a period of two weeks or more, it may be medically diagnosed as depression. </p>
<p>In the 1960s, researchers proposed that <a href="https://doi.org/10.1016/j.ssmmh.2022.100098">depression was caused by a chemical imbalance</a> of a neurotransmitter called serotonin in the brain. In 1988, the pharmaceutical company Eli Lilly introduced <a href="https://doi.org/10.1037%2Fa0038550">an antidepressant medication based on that idea</a>.</p>
<p>However, after decades of experiments, researchers have failed to find evidence showing support for the chemical imbalance theory. A recent study highlights the <a href="https://www.ucl.ac.uk/news/2022/aug/opinion-chemical-imbalance-theory-depression-clearing-some-misconceptions">growing realization that antidepressant medications</a> do not work <a href="https://doi.org/10.1038/s41380-022-01661-0">in the simplistic way</a> in which they <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313530/">have been advertised</a> for decades. </p>
<p>This is important because antidepressants have <a href="https://www.karger.com/Article/Abstract/447034">side effects</a> that can be serious. For a doctor and patient to weigh the risks and benefits of taking an antidepressant, they need accurate information about both. The chemical imbalance theory interfered with that conversation.</p>
<h2>Tools to heal depression</h2>
<p>So what exactly does contribute to overall well-being and happiness to help stave off depression?</p>
<p>A large body of research shows that <a href="https://doi.org/10.3390%2Fbrainsci11121633">biological, psychological and social factors</a> contribute to feeling satisfied in life or to developing depression. Because each individual is unique, there is not a one-size-fits-all formula for well-being. </p>
<p>Many people find relief from depression by talking to a psychotherapist. <a href="https://doi.org/10.1002%2Fwps.20238">High-quality psychotherapy</a> has been shown to be as effective as and <a href="http://dx.doi.org/10.1136/bmjopen-2012-002542">longer-lasting</a> <a href="https://doi.org/10.1038%2Fnrn2345">than antidepressant medication</a> when treating depression. </p>
<p>Therapy <a href="https://psycnet.apa.org/record/2017-55500-019">activates an individual’s hope</a> and natural resilience by <a href="https://doi.org/10.3389/fnint.2022.871227">creating a safe</a> and emotionally warm relationship through which the therapist and client work together toward common goals. In addition to helping clients learn about their emotions, thoughts, relationships and patterns of behavior, a good therapist explores how to help their clients identify everyday activities that can improve wellness.</p>
<p>The things we do on a day-to-day basis, called <a href="https://doi.org/10.1186/1471-244x-14-107">lifestyle factors</a>, function as building blocks for a life without depression. <a href="https://www.johnwbrickfoundation.org/move-your-mental-health-report/">Physical movement</a>, <a href="https://www.health.harvard.edu/blog/diet-and-depression-2018022213309">good nutrition</a>, <a href="https://www.nytimes.com/2013/11/19/health/treating-insomnia-to-heal-depression.html">healthy sleep</a>, <a href="https://www.apa.org/topics/mindfulness/meditation">healthy levels of stress</a> and <a href="https://doi.org/10.1037%2Fa0018555">stress management</a>, <a href="https://doi.org/10.1016/j.jad.2017.04.043">social connection</a>, <a href="https://www.healthexperiencesusa.org/Depression-in-Young-Adults/having-a-purpose-in-life">finding meaning and purpose</a> and <a href="https://doi.org/10.1007/s11126-020-09881-9">spiritual practices</a> all play important roles in preventing and treating depression. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/yTL_bNvXJ9s?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Exercise is a powerful antidote against depression, anxiety and stress.</span></figcaption>
</figure>
<p>These are too often wrongly trivialized as less effective than professional treatment. In fact, though, a <a href="https://theconversation.com/exercise-is-even-more-effective-than-counselling-or-medication-for-depression-but-how-much-do-you-need-200717">recent study</a> showed that exercise is <a href="http://dx.doi.org/10.1136/bjsports-2022-106195">even more effective than medication or counseling</a>. Another eye-opening study showed that <a href="https://doi.org/10.1097/01.nmd.0000217820.33841.53">85% of people who received no treatment</a> still recovered from depression within one year. </p>
<p>As mental health professionals, we find these results both humbling and inspiring. It means that the general public has solutions for depression that the mental health system has too often overlooked. This is consistent with the <a href="https://www.ifm.org/news-insights/healing-works-means-health-care-wayne-jonas-md/">scientific study of healing</a>, which shows that the body has a tremendous and overlooked <a href="https://www.youtube.com/watch?v=gcai0i2tJt0">ability to repair and heal itself</a> under the right circumstances. </p>
<p>Consider the example of <a href="https://doi.org/10.1016%2Fj.crphys.2021.04.002">laughter therapy</a>, a stress hormone-reducing, mood-lifting practice used in 120 countries. Laughter leaders guide <a href="https://laughteryogausa.org/">groups of people</a> in exercises that stimulate contagious laughter. Not everyone will react the same way to laughter therapy, but it is <a href="https://www.yogajournal.com/lifestyle/laughter-cure/">effective at increasing well-being for some people</a>, so it belongs in the tool box of therapies to try.</p>
<h2>Hope comes in many forms</h2>
<p>One research initiative has identified communities, <a href="https://doi.org/10.1177%2F1559827616637066">called blue zones</a>, where people tend to live long, healthy and satisfying lives. The lifestyles of people living in these areas, like Ikaria, Greece, and Okinawa, Japan, are characterized by social connection, consumption of mostly plant-based foods, a high sense of purpose, environments that support physical movement and intentional relaxation. Customs in different countries and environments show that these principles are visible across the globe in many different forms.</p>
<p>Many cultures extol the benefits of being in nature. <a href="https://www.bbc.com/worklife/article/20171211-friluftsliv-the-nordic-concept-of-getting-outdoors">Nordic countries use the word friluftsliv</a>, which means “outdoor life,” to describe the practice of getting outdoors to improve well-being. In Japan, <a href="https://www.japan.travel/en/guide/forest-bathing/">some people practice shinrin-yoku</a>, translated as forest bathing or opening up the senses to <a href="https://www.degruyter.com/document/doi/10.1515/revneuro-2015-0009/html">the natural world’s scents</a>, sights and sounds. </p>
<p>Researchers have also found that access to green space is associated with <a href="https://doi.org/10.3390%2Fijerph110303453">lower levels of depression symptoms</a>. Other studies <a href="https://doi.org/10.1016%2Fj.pmedr.2016.11.007">show that gardening is linked with</a> less depression, stronger social connections and improvement in quality of life. Gardening also gives those with access a chance to move their bodies and eat more homegrown vegetables as part of an <a href="https://doi.org/10.1186/s12888-022-03771-z">anti-depression nutrition plan</a>. </p>
<p>We cannot describe everything on the endless list of life-affirming, research-supported and low-risk methods to decrease stress, boost mood and enhance fulfillment. But here are a few more examples: </p>
<ul>
<li><a href="https://doi.org/10.1155/2017/5869315">aromatherapy</a></li>
<li><a href="https://www.health.harvard.edu/blog/light-therapy-not-just-for-seasonal-depression-202210282840">light therapy</a></li>
<li><a href="https://doi.org/10.1177%2F2156587217715927">yoga</a></li>
<li><a href="https://doi.org/10.3389/fpsyg.2021.647879">music</a></li>
<li><a href="https://www.helpguide.org/articles/mental-health/mood-boosting-power-of-dogs.htm">animals</a></li>
<li><a href="https://www.artandhealing.org/health-concerns/">making art</a> </li>
<li><a href="https://www.cdc.gov/howrightnow/gratitude/index.html#">gratitude practice</a> </li>
<li><a href="https://psycnet.apa.org/doi/10.1037/emo0000324">sexual activity</a> </li>
<li><a href="https://ppc.sas.upenn.edu/">positive psychology</a></li>
<li><a href="https://www.psychologytoday.com/us/blog/the-athletes-way/202008/beyond-fun-and-games-playfulness-may-help-combat-depression#">playfulness enhancement</a></li>
<li><a href="https://doi.org/10.2196%2Fjmir.6482">mobile</a> <a href="https://screening.mhanational.org/content/what-are-best-apps-depression/">apps</a></li>
<li>self-help <a href="https://doi.org/10.1177%2F2515690X18823691">tools like “tapping”</a> to help with strong emotions</li>
<li><a href="https://www.artandhealing.org/unlonely-project/">peer and social</a> <a href="https://mystrength.com/">support programs</a> </li>
</ul>
<p>These seemingly simple interventions are powerful because they lead to health-promoting psychological and <a href="https://www.ncbi.nlm.nih.gov/books/NBK541120/">physiological changes</a>. </p>
<h2>Staying true to what works</h2>
<p>Clinicians, researchers and <a href="https://www.wired.com/2017/05/star-neuroscientist-tom-insel-leaves-google-spawned-verily-startup/">leaders</a> have been trying to identify the <a href="https://clinicaltrials.gov/ct2/show/NCT00021528">best treatment for depression</a> for at least two decades. </p>
<p>This is an unanswerable question. Some treatments work extremely well for certain people and cause terrible reactions for others. When <a href="http://dx.doi.org/10.1136/adc.2004.058222">standard research protocols</a> try to capture these effects, it can <a href="https://doi.org/10.1111/j.0887-378X.2004.00327.x">look like there is no effect of the treatment</a> because the positive effects average out with the negative effects. </p>
<p>A search for the holy grail of a <a href="https://doi.org/10.1016/j.neubiorev.2017.08.019">neurobiological cause for depression</a> has drawn attention away from efforts to implement what is already known about how to <a href="https://www.who.int/europe/about-us/our-work/core-priorities/promoting-health-and-well-being">promote health</a>. </p>
<p>To <a href="https://www.cdc.gov/hrqol/wellbeing.htm#one">live one’s best life</a>, everyone needs safety, shelter, clothing, good nutrition, good sleep, physical movement, <a href="https://doi.org/10.1007/s12671-020-01375-w">loving and kind social connection</a> and a sense of meaning and purpose. There are many ways to help people get there.</p><img src="https://counter.theconversation.com/content/198282/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>An overreliance on medication as the first-line treatment for depression can lead some people to be labeled with treatment-resistant depression when there are other viable alternatives for relief.Elissa H. Patterson, Clinical Assistant Professor of Psychiatry and Neurology, University of MichiganJay Kayser, PhD Student in Social Work and Developmental Psychology, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1988802023-02-27T19:16:01Z2023-02-27T19:16:01ZConsidering going off antidepressants? Here’s what to think about first<figure><img src="https://images.theconversation.com/files/511353/original/file-20230221-20-otku8g.jpg?ixlib=rb-1.1.0&rect=20%2C0%2C6689%2C3780&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">sh</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/black-girl-hold-white-pills-jar-1702567036">Shutterstock</a></span></figcaption></figure><p>Mental health is key to health and wellbeing. Yet two in five Australians aged 16 to 85 (44%) <a href="https://www.aihw.gov.au/reports/mental-health-services/mental-health">experience a mental illness</a> during their lifetime, commonly anxiety or depression. And more than <a href="https://www.aihw.gov.au/mental-health/topic-areas/mental-health-prescriptions">32 million</a> antidepressant prescriptions are dispensed on the Pharmaceutical Benefits Scheme each year for these diagnoses. </p>
<p>Use of antidepressants has <a href="https://pubmed.ncbi.nlm.nih.gov/34963328/">increased</a> since the beginning of the COVID pandemic at a greater rate than past decades. As we return to some semblance of normality, people may well be thinking about going off their mental health medicines, particularly antidepressants. </p>
<p>But what are the risks of stepping down or stopping these medicines? Here’s what to consider.</p>
<h2>Is there ever a good time to stop antidepressants?</h2>
<p>It can take several weeks after starting an antidepressant before symptoms begin to improve. During this time, the person may feel worse before they feel better, as side effects often occur before symptoms improve. Troublesome symptoms (nausea, diarrhoea or insomnia) will <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181894/">usually improve</a> once the body adjusts to the new medicine. So, it is important to give the antidepressant a “fair go” and not stop too early in this process.</p>
<p>For people who have been diagnosed with their first episode of anxiety or depression and are responding to their antidepressant, <a href="https://www.nice.org.uk/guidance/ng222/chapter/recommendations">guidelines</a> recommend a six- to 12-month duration of use, followed by medical review to assess if taking medication is still indicated.</p>
<p>Of course, there are reasons you might be thinking about discontinuing your antidepressant. They could include:</p>
<ul>
<li><p>no longer experiencing symptoms of depression or anxiety</p></li>
<li><p>finding other ways of coping</p></li>
<li><p>medicine seeming ineffective</p></li>
<li><p>long-term use and wanting a break</p></li>
<li><p>a life event such as pregnancy, divorce or job change</p></li>
<li><p>media influences, such as reports about treatments or portrayals of people taking similar medications</p></li>
<li><p>side effects, stigma or pressure from family and friends.</p></li>
</ul>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-chemical-imbalance-theory-of-depression-is-dead-but-that-doesnt-mean-antidepressants-dont-work-187769">The chemical imbalance theory of depression is dead, but that doesn't mean antidepressants don't work</a>
</strong>
</em>
</p>
<hr>
<h2>Go slowly</h2>
<p>In animal studies, <a href="https://pubmed.ncbi.nlm.nih.gov/36057649/">restricted plasticity in specific brain parts </a> (that is, the brain’s ability to modify connections or rewire itself) can cause features of depression or anxiety. How antidepressants work is not completely understood. However, <a href="https://pubmed.ncbi.nlm.nih.gov/34053675/">recent evidence</a> suggests they protect against or reverse some of these maladaptive neuroplastic changes. </p>
<p>Beneficial effects take time, and stopping antidepressants quickly can unwind the medicine’s neurophysiological adaptations. This can create a “shock to the system” and potentially lead to unwanted side effects such as withdrawal symptoms. </p>
<p>Slower reduction allows the brain time to gradually readjust.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-tga-has-approved-certain-psychedelic-treatments-the-response-from-experts-is-mixed-199290">The TGA has approved certain psychedelic treatments: the response from experts is mixed</a>
</strong>
</em>
</p>
<hr>
<h2>What can go wrong when you abruptly stop antidepressants?</h2>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/36400895/">Stopping antidepressants abruptly</a>, especially after a long period of use, will make most people – although not everyone – unwell. It’s impossible to tell in advance who will be affected, so slow dose reduction is advisable.</p>
<p>Stopping antidepressants (or tapering down the dose) too rapidly can cause <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449237/">antidepressant discontinuation syndrome</a> in around 20% of people. </p>
<p>Withdrawal symptoms are variable but can include flu-like symptoms (lethargy, fatigue, headache, achiness, sweating), insomnia, nausea (sometimes vomiting), dizziness, sensory disturbances (such as burning or tingling) and hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness). </p>
<p>Symptoms typically occur within ten days and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970174/">usually resolve</a> in two to three weeks. But occasionally, a protracted withdrawal syndrome lasting many months can occur. </p>
<p>People who’ve had irregular doses, switched antidepressants, overlooked side-effects or previous withdrawal symptoms are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970174/">more likely</a> to experience protracted symptoms and take longer to recover.</p>
<h2>Is this withdrawal or a relapse?</h2>
<p>In mental illness, the cause of symptoms can be difficult to differentiate. Antidepressant side-effects can mimic withdrawal symptoms or disease relapse, causing confusion for both patients and prescribers.</p>
<p><iframe id="DU2ve" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/DU2ve/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Withdrawal symptoms tend to <a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.18060692">surge irregularly</a> like waves. This makes them different to a relapse of the original condition, which has a more consistent pattern and <a href="https://pubmed.ncbi.nlm.nih.gov/16456219/">takes longer</a> to develop.</p>
<p>Antidepressant discontinuation is an important decision. Consider whether you are in the right mindset to make this change. Work with a trusted mental health professional to tailor a strategy for your individual circumstances to minimise withdrawal or relapse risk. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="woman sits on couch with hands clasped" src="https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511354/original/file-20230221-18-pluj3c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Chat to your prescriber about tapering down slowly at the right time.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/woman-clasped-her-hands-lap-closed-1756005818">Shutterstock</a></span>
</figcaption>
</figure>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/can-taking-vitamins-and-supplements-help-you-recover-from-covid-182220">Can taking vitamins and supplements help you recover from COVID?</a>
</strong>
</em>
</p>
<hr>
<h2>4 things to think about</h2>
<p>Once you’ve considered your reasons for wanting to stop taking an antidepressant and whether you’ve given it a fair shot to work, think about whether you feel well physically and emotionally and have supportive people in your life.</p>
<p>If you still want to embark on a process of stepping down or ceasing medication:</p>
<p><strong>1. approach your prescriber</strong> honestly with your reasons for discontinuation and work towards a shared decision to reduce the dose</p>
<p><strong>2. plan dose reduction</strong> at a rate suitable for your personal health and duration of antidepressant use (months versus years). Longer use requires a longer taper. Dose reduction can be by as little as 10% or as much as 25% every one to two weeks, followed by another two to four weeks when you can observe how you feel and manage the reduced dose. If symptoms are tolerable, continue tapering as before. But be prepared to move back to the previous or a 10% dose increase if symptoms emerge</p>
<p><strong>3. monitor any symptoms</strong> and health by using a daily diary that records the drug dosage throughout the taper</p>
<p><strong>4. maximise the chances of success</strong> with self-care: a healthy diet, regular exercise and sleep.</p>
<p>Every medicine we take should have a reassessment date. People taking antidepressants should have their medication reviewed no later than 12 months after they started. </p>
<p>This gives an opportunity for the patient to discuss the risks versus benefits of remaining on their medicine or developing a shared strategy for safe discontinuation.</p><img src="https://counter.theconversation.com/content/198880/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Treasure McGuire does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>There are lots of reasons someone might want to stop taking antidepressants, from a life change to wanting to take a break. But the process of tapering off medications needs to be carefully managed.Treasure McGuire, Assistant Director of Pharmacy, Mater Health SEQ in conjoint appointment as Associate Professor of Pharmacology, Bond University and Associate Professor (Clinical), The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1975142023-01-12T21:26:23Z2023-01-12T21:26:23ZA fishy problem: How antidepressants may impact the health of our aquatic ecosystems<figure><img src="https://images.theconversation.com/files/504080/original/file-20230111-17-xprb39.png?ixlib=rb-1.1.0&rect=28%2C25%2C1833%2C998&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The rising use of antidepressants has led to a parallel spike in their presence in our ecosystems.</span> <span class="attribution"><span class="source">(Tammy Rodela)</span>, <span class="license">Author provided</span></span></figcaption></figure><p>The use of antidepressant pills has become synonymous with improved mental health, quelling sometimes crippling anxiety, and altering energy levels and behaviour. They are heavily relied upon when <a href="https://doi.org/10.1007/s40199-021-00390-z">treating depression</a> and <a href="https://doi.org/10.31887/DCNS.2017.19.2/bbandelow">general anxiety disorder</a>. </p>
<p>In the past 20 years, European nations have seen consumption rates of antidepressants <a href="https://www.oecd-ilibrary.org/sites/43146d4b-en/index.html?itemId=/content/component/43146d4b-en">more than double</a>. Closer to home, their usage amongst Canadian youth <a href="https://doi.org/10.1089/cap.2019.0121">is surging</a>. In the shadow of the COVID-19 pandemic, <a href="https://doi.org/10.1017%2FS0033291722001891">these rates are only expected to rise</a>, particularly when considering the affordability of and need for these medications.</p>
<p>However, many people are likely unaware of a hidden and perhaps surprising environmental cost associated with antidepressant usage. The rising use of antidepressants has led to a parallel spike in their presence in our ecosystems.</p>
<p>As a developmental toxicologist who has been studying the impact of our actions on aquatic life, I investigate the impacts of antidepressants on fish. Identifying and characterizing the potential damage to fish exposed to these neuroactive compounds is paramount for protecting the biodiversity of our aquatic ecosystems. </p>
<h2>Antidepressants and aquatic environments</h2>
<p>Our bodies do not fully break down each pill we take and the by-products released from our bodies are often <a href="https://psychscenehub.com/psychinsights/venlafaxine-and-desvenlafaxine-pharmacology/">just as active as the original medication</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/OYbRlJLBzn4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The active byproducts of antidepressants expelled by our bodies can survive wastewater treatment, and end up entering our ecosystems.</span></figcaption>
</figure>
<p>Our toilets carry these neuroactive ingredients that affect nervous systems into our wastewater. Despite best attempts to treat them, not all the components of antidepressants <a href="https://doi.org/10.1016%2Fj.cscee.2020.100074">can be removed</a> from our sewage. </p>
<p>So, treated municipal wastewater is released into our ecosystems, containing the remnants of antidepressants people consume. </p>
<p><a href="https://doi.org/10.1002/etc.27">Antidepressants are accumulating in our waterways today</a>. They break down significantly slower than we replenish them, and the global scorecard shows that they have reached record levels.</p>
<h2>Antidepressants and fish</h2>
<p>Research has found the neuroactive compounds of antidepressants <a href="https://doi.org/10.1021/acs.est.7b02912">in the livers, brains and reproductive organs of various fish species</a>. </p>
<p>These pills offer people balance and reprieve by altering their levels of neurotransmitters. These are signalling molecules in our bodies that orchestrate movement and regulate how our bodies perform daily activities.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Fluorescent image of a fish brain" src="https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/504173/original/file-20230112-46586-uejugp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Serotonin imaging revealed that antidepressants can alter zebrafish’s serotonin levels during their development.</span>
<span class="attribution"><span class="source">(William Andrew Thompson)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Despite the glaring differences between humans and fish, the underpinnings of our physiology and neural networks <a href="https://doi.org/10.1242/dmm.015545">share similarities</a>. It’s not surprising that antidepressants affect fish in many ways, and the evidence <a href="https://doi.org/10.3389/fendo.2022.895064">suggests their impacts are specific</a> to the life-stage of each fish.</p>
<p>Research has found that today’s environmental levels of antidepressants can <a href="https://doi.org/10.1016/j.chemosphere.2020.127437">alter fish behaviour</a>. Changes in fish behaviour are significant because their ability to acquire food, seek shelter and breed requires nuanced movements. Even a small change in the delicate balance between the energy derived from food and that required to obtain it can have a huge impact.</p>
<p>Apart from fish behaviour, antidepressants alter systems necessary for species survival. For example, antidepressants that target serotonin can influence the quality and abundance of <a href="https://pubmed.ncbi.nlm.nih.gov/28622660/">fish eggs</a> and <a href="https://doi.org/10.1016/j.scitotenv.2018.09.294">sperm</a>. They can change <a href="https://doi.org/10.1152/physiolgenomics.90263.2008">the hormones</a> that guide the development and function of reproductive tissues.</p>
<p>My research on Effexor (venlafaxine), a highly-prescribed antidepressant that changes levels of <a href="https://my.clevelandclinic.org/health/articles/22572-serotonin#:%7E:text=Serotonin%20is%20a%20chemical%20that,blood%20clotting%20and%20sexual%20desire.">serotonin</a> and <a href="https://my.clevelandclinic.org/health/articles/22610-norepinephrine-noradrenaline#:%7E:text=Norepinephrine%20(Noradrenaline),short%2Dterm%20serious%20health%20situations.">norepinephrine</a>, has revealed that this drug has the capacity to <a href="https://doi.org/10.1021/acs.est.7b04099">influence the brain development of fish</a>. The most pronounced changes seem to be in the same <a href="https://doi.org/10.1021/acs.est.0c06032">systems that the antidepressant targets</a> in humans.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1404838608071139330"}"></div></p>
<p>Early-life exposures to antidepressants can leave long-lasting impressions on fish development. Antidepressants like Prozac (fluoxetine) <a href="https://doi.org/10.1073/pnas.1811695115">can influence how fish produce cortisol</a> — the saviour stress hormone that lets us respond to tough times in our lives. Moreover, these drugs have been shown on several occasions to <a href="https://doi.org/10.3389/fendo.2022.895064">influence how fish grow</a>, possibly reducing the ability of smaller fish to survive in the wild.</p>
<h2>Using antidepressants with care</h2>
<p>While it is unclear whether or not antidepressants explicitly lead to the reduced survival of fish, studies have found that antidepressants, specifically at current environmental levels, are <a href="https://doi.org/10.1016/j.chemosphere.2020.127437">sufficient to influence how fish perform and function</a>.</p>
<p>Higher levels only add to these effects. Recently, medical experts <a href="https://doi.org/10.1136/bmj.f191">have suggested</a> that despite their apparent benefits of antidepressants, these pills may be over-prescribed. This is concerning, particularly given the <a href="https://doi.org/10.3389/fphar.2018.00239">addictive potential</a> of several commonly prescribed antidepressants.</p>
<p>While antidepressants seem to have become a first response for treating depression (and other conditions), <a href="https://www.bmj.com/company/newsroom/prescribe-fewer-antidepressants-and-for-shorter-periods-doctors-advised/">some experts in psychiatry and pharmaceutical researchers have argued</a> that <a href="https://doi.org/10.1186%2F1471-244X-14-107">therapy and lifestyle changes</a> are sufficient to <a href="https://www.health.harvard.edu/mind-and-mood/the-no-drug-approach-to-mild-depression">combat most minor and moderate iterations of the disease</a>.</p>
<p>If antidepressant usage continues to increase, these levels could reach critical thresholds, not just for fish, but for other animals and people too. And unfortunately this may come at the cost of the ecosystem — a price humanity cannot afford to pay.</p><img src="https://counter.theconversation.com/content/197514/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Andrew Thompson is currently a MITACS Postdoctoral Fellow in the Department of Biology at McMaster University. He was awarded the Eyes High doctoral scholarship at the University of Calgary, with his doctoral work further supported by an NSERC grant awarded to Dr. Matt Vijayan. </span></em></p>Neuroactive compounds in antidepressants enter our wastewater and affect how fish function. Identifying the potential damage to fish is paramount for protecting our aquatic ecosystems.William Andrew Thompson, Post-doctoral Fellow, Department of Biology, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1867372022-11-16T13:29:25Z2022-11-16T13:29:25ZPatients suffering with hard-to-treat depression may get relief from noninvasive magnetic brain stimulation<figure><img src="https://images.theconversation.com/files/477266/original/file-20220802-18-nnapcv.jpg?ixlib=rb-1.1.0&rect=15%2C0%2C5218%2C3931&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Transcranial magnetic stimulation has worked when medication and other therapies have not.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/patient-in-transcranial-magnetic-stimulation-royalty-free-image/548557027?adppopup=true">Monty Rakusen/Image Source via Getty Images</a></span></figcaption></figure><p>Not only is depression a debilitating disease, but it is also widespread. Approximately 20 million adult Americans experience at least <a href="https://www.nimh.nih.gov/health/statistics/major-depression">one episode of depression per year</a>. </p>
<p>Millions of them <a href="https://www.cdc.gov/nchs/products/databriefs/db377.htm#:">take medication</a> to treat their depression. But for many, the <a href="https://www.webmd.com/depression/guide/treatment-resistant-depression-what-is-treatment-resistant-depression">medications don’t work</a>: Either they have minimal or no effect, or the side effects are intolerable. These patients have what is called <a href="https://www.mayoclinic.org/diseases-conditions/depression/in-depth/treatment-resistant-depression/art-20044324">treatment-resistant depression</a>. </p>
<p>One promising treatment for such patients is a type of brain stimulation therapy <a href="https://www.healthline.com/health/tms-therapy#What-is-TMS-therapy">called transcranial magnetic stimulation</a>. </p>
<p>This treatment is not new; it has been around since 1995. The U.S. Food and Drug Administration <a href="https://doi.org/10.1016/j.brs.2021.11.010">cleared transcranial magnetic stimulation in 2008</a> for adults with “non-psychotic treatment-resistant depression,” which is typically defined as a failure to respond to two or more antidepressant medications. More recently, in 2018, the FDA cleared it for <a href="https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-transcranial-magnetic-stimulation-treatment-obsessive-compulsive-disorder#">some patients with obsessive-compulsive disorder</a> and <a href="https://www.fda.gov/consumers/consumer-updates/want-quit-smoking-fda-approved-and-fda-cleared-cessation-products-can-help#">smoking cessation</a>. </p>
<p>Insurance <a href="https://www.mytransformations.com/post/the-ultimate-guide-to-tms-therapy-and-insurance-coverage">generally covers these treatments</a>. Both the psychiatrist and the equipment operator must be certified. While the treatment has been available for years, the equipment to perform the procedure remains expensive enough that few private psychiatry practices can afford it. But with the growing recognition of the potential of transcranial magnetic stimulation, the price will likely eventually come down and access will be greatly expanded.</p>
<h2>Does it work?</h2>
<p>Transcranial magnetic stimulation is a noninvasive, pain-free procedure that has minimal to no side effects, and it often works. Research shows that 58% of once treatment-resistant patients experience <a href="https://doi.org/10.1002/da.21969">a significant reduction in depression</a> following four to six rounds of the therapy. More than 40 independent clinical trials – with more than 2,000 patients worldwide – have demonstrated that repetitive transcranial magnetic stimulation <a href="https://doi.org/10.1136/gpsych-2019-100074">is an effective therapy</a> for the treatment of resistant major depression. </p>
<p><a href="https://medicine.fiu.edu/about/faculty-and-staff/profiles/psychiatry-and-behavioral-health/junquera,-patricia.html">As a professor and psychiatrist</a> who has used transcranial magnetic stimulation to treat some of my patients, I have seen depression symptoms decrease even within the first two weeks of treatment. What’s more, the effects continue after the treatment has ended, typically for six months to a year. After that, the patient has the option of maintenance treatment. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/pfy0t5Yapco?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Transcranial magnetic stimulation helps increase blood flow and dopamine levels in the brain.</span></figcaption>
</figure>
<h2>About the procedure</h2>
<p>For the patient, the procedure is easy and simple. One sits in a comfortable chair with a snug pillow that holds their head in place, puts on earplugs and can then relax, check their phone, watch TV or read a book.</p>
<p>A treatment coil, which looks like a figure 8, is placed on the patient’s head. A nearby stimulator sends an electrical current to the coil, which transforms the current into <a href="https://www.livescience.com/38059-magnetism.html">a magnetic field</a>. </p>
<p>The field, which is highly concentrated, turns on and off rapidly while targeting a portion <a href="https://neuroscientificallychallenged.com/posts/know-your-brain-prefrontal-cortex">of the prefrontal cortex</a> – the area of the brain responsible for mood regulation. </p>
<p>Researchers know that people suffering from depression have reduced blood flow and less activity in that part of the brain. Transcranial magnetic stimulation causes increases in both blood flow and in the levels of <a href="https://www.healthdirect.gov.au/dopamine#">dopamine</a> and <a href="https://doi.org/10.1007/s00702-014-1180-8">glutamate</a> – two neurotransmitters that are responsible for brain functions like concentration, memory and sleep. It’s the repeated stimulation of this area – the “depression circuit” of the brain – that brings the antidepressant effect. </p>
<h2>It is not ‘electroshock’ or deep brain stimulation</h2>
<p>Some people confuse transcranial magnetic stimulation with <a href="https://www.psychiatry.org/patients-families/ect#">electroconvulsive therapy</a>, a procedure used for patients with severe depression or catatonia. With electroshock therapy, the anesthetized patient receives a direct electrical current, which causes a seizure. Typically, people who undergo this procedure experience <a href="https://www.mayoclinic.org/tests-procedures/electroconvulsive-therapy/about/pac-20393894#:">some memory loss after treatment</a>. </p>
<p>Transcranial magnetic stimulation is very different. It doesn’t require anesthesia, and it doesn’t affect memory. The patient can resume daily activities right after each treatment. Dormant brain connections are reignited without causing a seizure.</p>
<p>It should also not be confused with <a href="https://www.mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac-20384562">deep brain stimulation</a>, which is a surgical procedure used <a href="https://theconversation.com/deep-brain-stimulation-can-be-life-altering-for-ocd-sufferers-when-other-treatment-options-fall-short-186109">to treat obsessive-compulsive disorder</a>, tremors, epilepsy and Parkinson’s disease. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/a_8bOCNjJpY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Transcranial magnetic stimulation stimulates the ‘depression circuit’ in the brain.</span></figcaption>
</figure>
<h2>Side effects and access</h2>
<p>Transcranial magnetic stimulation patients undergo a total of <a href="https://www.mindpath.com/resource/what-a-typical-tms-treatment-looks-like/">36 treatments, at 19 minutes each</a>, for three to six weeks. Research has concluded that this is the best protocol for treatment. Some patients report that it feels like someone is tapping on their head. Others don’t feel anything. </p>
<p>Some very minor side effects may occur. The most common is facial twitching and scalp discomfort during treatment, sensations that go away after the session ends. Some patients report a mild headache or discomfort at the application site. Depending on how effective the therapy was, some patients return for follow-ups every few weeks or months. It can be used in addition to medications, or with no medication at all. </p>
<p>Not everyone with depression can undergo <a href="https://www.clinicaltmssociety.org/content/who-cannot-have-tms">this type of brain stimulation therapy</a>. Those with epilepsy or a history of head injury may not qualify. People with metallic fillings in their teeth are OK for treatment, but others with implanted, nonremovable metallic devices in or around the head are not. Those with pacemakers, defibrillators and vagus nerve stimulators may also not qualify, because the magnetic force of the treatment coil may dislodge these devices and cause severe pain or injury. </p>
<p>But for those who are able to use the therapy, the results can be remarkable. For me, it is amazing to see these patients smile again – and come out on the other side feeling hopeful.</p><img src="https://counter.theconversation.com/content/186737/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia Junquera does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Patients who undergo transcranial magnetic stimulation say it’s painless, with few to no side effects. The treatment isn’t yet widely accessible, but for those who use it, the effects can be profound.Patricia Junquera, Associate Professor and Vice Chair of Clinical Services, Florida International UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1861092022-09-28T12:32:58Z2022-09-28T12:32:58ZDeep brain stimulation can be life-altering for OCD sufferers when other treatment options fall short<figure><img src="https://images.theconversation.com/files/486344/original/file-20220923-8064-5j7otz.jpg?ixlib=rb-1.1.0&rect=1161%2C23%2C6826%2C4467&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Deep brain stimulation relies on thin electrodes implanted deep in the brain that deliver electrical currents. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/artificial-intelligence-digital-concept-royalty-free-image/1283240410">Olemedia/E+ via Getty Images</a></span></figcaption></figure><p>Imagine growing up tormented by fears and life-consuming rituals that make no sense to you or those around you. Then imagine the shame of being told by mental health providers that, because you understand that your behaviors are illogical but keep doing them anyway, you must want to stay sick. </p>
<p>One of my patients, Moksha Patel, who is a doctor himself, endured this from childhood until his early 30s. In September 2021, Patel underwent deep brain stimulation surgery, a rare neurosurgical procedure that can be used for severe obsessive-compulsive disorder, or OCD, when it has been resistant to less invasive treatments. </p>
<hr>
<iframe id="noa-web-audio-player" style="border: none" src="https://embed-player.newsoveraudio.com/v4?key=x84olp&id=https://theconversation.com/deep-brain-stimulation-can-be-life-altering-for-ocd-sufferers-when-other-treatment-options-fall-short-186109&bgColor=F5F5F5&color=D8352A&playColor=D8352A" width="100%" height="110px"></iframe>
<p><em>You can listen to more articles from The Conversation, narrated by Noa, <a href="https://theconversation.com/us/topics/audio-narrated-99682">here</a>.</em></p>
<hr>
<p>Patel has consented to this publication of his medical information. He <a href="https://news.cuanschutz.edu/news-stories/ocd-ruled-moksha-patels-life-until-a-rare-surgical-procedure-changed-everything">shares his story publicly</a> to combat stigma and to provide hope for other sufferers that relief is possible. </p>
<p>The term OCD is thrown around casually, often by someone joking about how organized they are: “I’m so OCD.” But true <a href="https://doi.org/10.1176/ajp.153.6.783">obsessive-compulsive disorder is debilitating</a> and leads to <a href="https://doi.org/10.1007/s40263-013-0056-z">significant suffering</a>. </p>
<p>I <a href="https://som.ucdenver.edu/Profiles/Faculty/Profile/13845">lead a team</a> that treats people with OCD using <a href="https://medschool.cuanschutz.edu/psychiatry/PatientCare/obsessive-compulsive-disorder-program">evidence-based approaches</a>. I am also co-director of the <a href="https://medschool.cuanschutz.edu/psychiatry/PatientCare/obsessive-compulsive-disorder-program/reclaim-deep-brain-stimulation-therapy-for-ocd">OCD surgical program</a> at the University of Colorado, Anschutz campus, and UC Health, a nonprofit health care system in Colorado. </p>
<p>Our surgical program is one of the few academic centers in the U.S. that offer deep brain stimulation for the treatment of OCD. My experience and research have given me insight into how a rare procedure can be used in <a href="https://doi.org/10.3389/fpsyt.2021.568932">real-world settings</a> to provide relief to those who suffer from OCD when other less invasive treatments have not been successful.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/4euYnqMWT5w?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Dr. Sabine Wilhelm of Mass General Hospital answers the most commonly searched questions about obsessive-compulsive disorder.</span></figcaption>
</figure>
<h2>What does OCD feel like for a sufferer?</h2>
<p>A brain with OCD is primed to detect any signs of potential danger. Many people with OCD <a href="https://iocdf.org/blog/2019/04/22/what-it-feels-like-to-live-with-ocd/">wake up every day with a sense of dread</a> and an expectation of bad things happening. Daily life is overshadowed by ever-present guilt, shame, fear and doubt. As a result, they carry out compulsive and repetitive activities to attempt to forestall disaster and manage the painful emotions. </p>
<p>OCD fears most often involve the things and people that matter the most to the sufferer, such as their values, loved ones or purpose in life. For example, someone who values kindness and compassion might fear that they will offend, betray or somehow hurt the people they care about.</p>
<p>Sometimes what is hardest for someone who suffers with OCD is a recognition that the fears and behaviors are illogical – insight that provides no relief. </p>
<p>And because other people usually don’t understand, those with OCD do their best to hide their illness so they won’t be judged as ridiculous or “crazy,” which often leads to long delays in diagnosis and treatment. This is a painful and lonely life for the approximately <a href="https://www.psychiatrist.com/jcp/ocd/ocd-prevalence-and-gender/">1%-2% of the world population with OCD</a>. </p>
<h2>Current OCD treatment options</h2>
<p>The best initial treatment for OCD is a type of mental health therapy called <a href="https://www.erp4ocd.com/">exposure and response prevention</a>. During these sessions, OCD sufferers are supported in gradually confronting their fears while also limiting the behaviors they have come to associate with providing safety. </p>
<p>For instance, someone with a fear of harming others might start by sitting near a butter knife and work their way up to holding a sharper knife to their therapist’s throat. They either learn that their fear does not play out, or – in the case of fears that cannot be disproved – that they can tolerate their anxiety or distress and move forward even in the absence of certainty. </p>
<p>The primary <a href="https://iocdf.org/about-ocd/ocd-treatment/meds/">medications used to treat OCD</a> are <a href="https://www.fda.gov/drugs/information-drug-class/selective-serotonin-reuptake-inhibitors-ssris-information">serotonin reuptake inhibitors, or SRIs/SSRIs</a>, which are commonly prescribed for treatment of depression and anxiety. But when used for OCD, these medications are typically prescribed at much higher dosages.</p>
<p>Unfortunately, <a href="https://doi.org/10.4088/jcp.v67n0214">OCD is a chronic condition</a> for most; studies show that only 65% of people with OCD respond to standard treatment, which is a combination of therapy and medication, and only about 35% recover completely. About 10% of individuals with OCD <a href="https://doi.org/10.1186/s12888-014-0214-y">remain severely impaired</a>, regardless of how intensively they are treated.</p>
<h2>The potential of deep brain stimulation</h2>
<p>For this small group of individuals with severe and persistent OCD, deep brain stimulation – a procedure that <a href="http://dx.doi.org/10.5498/wjp.v11.i9.659">fewer than 400 people</a> with OCD have undergone worldwide – provides hope. </p>
<p>Patel, an internal medicine doctor, first came to my office in 2019. He is one of 13 patients I’ve worked with to provide deep brain stimulation for OCD and other psychiatric illnesses.</p>
<p>He has suffered with OCD since the age of 4 or 5, with obsessive fears about germs, contamination and social interactions, among other things. He learned to function and succeed by shaping his life around his rituals – for example, by not consuming water or food at work so that he would not need to use public restrooms. </p>
<p>Patel, like many others with OCD, is conscientious, thorough and compassionate, traits that contribute to his success as a physician. However, before deep brain stimulation, most of his life outside of work was occupied by painful, consuming rituals. These included scrubbing himself with harsh chemicals for hours. </p>
<p>He had explored every treatment he could find, seeing 13 mental health providers since high school and participating in years of exposure therapy. He had tried at least 15 different medications, all with little benefit. Then he learned that deep brain stimulation was available at the hospital where we both work. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A neurosurgeon prepares his patient, who is lying down, for deep brain stimulation surgery." src="https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/486645/original/file-20220926-8644-62d70o.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Dr. Steven Ojemann, a CU Anschutz/UCHealth neurosurgeon, preparing Dr. Moksha Patel for deep brain stimulation surgery on Sept. 15, 2021.</span>
<span class="attribution"><span class="source">Radhika Patel</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<h2>How deep brain stimulation works</h2>
<p>Deep brain stimulation requires a neurosurgical procedure to place thin electrodes into deep structures of the brain, specifically a region known as the <a href="https://doi.org/10.1016/j.wneu.2019.01.254">ventral capsule/ventral striatum</a>. These <a href="https://www.youtube.com/watch?v=wYLJGuUt4iI">electrodes deliver electrical currents to the brain</a>. The current is produced by pulse generators in the chest that look much like cardiac pacemakers. They are connected to the electrodes in the brain by wires tunneled beneath the skin.</p>
<p>We researchers do not yet have a precise understanding of exactly how deep brain stimulation works, but we do know that it <a href="https://doi.org/10.1038/nn.3344">normalizes the communication</a> between parts of the brain responsible for taking in information and those responsible for acting on this information. These areas are hyperconnected in people with OCD, leading to a reduced ability to make thoughtful, value-driven decisions and an over-reliance on <a href="https://doi.org/10.1038/s41380-020-01007-8">reflexive or habitual behaviors</a>. And the changes induced by deep brain stimulation correlate with a reduction in OCD symptoms.</p>
<p>This type of neurostimulation is most commonly used to manage symptoms of <a href="https://www.nia.nih.gov/health/parkinsons-disease">Parkinson’s disease</a>, a movement disorder that leads to tremors and body rigidity. OCD is the only psychiatric disorder that currently has approval from the Food and Drug Administration for deep brain stimulation treatment. But deep brain stimulation <a href="https://doi.org/10.3171/2015.3.FOCUS1546">has been investigated</a> in <a href="https://doi.org/10.1016/j.neuroimage.2020.117515">other conditions, including major depression</a>, Tourette syndrome, schizophrenia, substance use disorders, post-traumatic stress disorder and eating disorders. </p>
<p>Deep brain stimulation is a procedure of last resort for patients with OCD. Because of the invasive nature of brain surgery and the potential for <a href="https://doi.org/10.1016/j.neubiorev.2020.01.007">serious adverse effects</a> such as infection or hemorrhage, individuals need to try standard, less invasive treatments first and meet the <a href="https://doi.org/10.3389/fpsyt.2021.706181">criteria for severe and persistent OCD</a>, which have been established based on OCD and brain stimulation research. </p>
<p>But for those who do undergo the procedure for OCD treatment and receive ongoing stimulation, <a href="https://doi.org/10.1038/mp.2008.55">up to 70%</a> have a <a href="http://dx.doi.org/10.5498/wjp.v11.i9.659">good long-term response</a>. “Good” is considered to be a 35% reduction in OCD symptoms based on a <a href="https://doi.org/10.1001/archpsyc.1989.01810110048007">standardized scale for obsessive-compulsive behavior</a> that experts in our field rely on. </p>
<p>This, for example, could mean that someone goes from spending more than eight hours per day on OCD behaviors and not leaving the house at all to spending four hours per day and being able to go to school with significant support. Such progress is remarkable, given how ill these individuals are.</p>
<h2>Barriers and stigma</h2>
<p>There aren’t very many treatment centers anywhere in the world, so patients who need this procedure may have trouble getting to one. Additionally, as our team has described in published research, getting insurance coverage for the procedure is <a href="https://doi.org/10.1038/s41591-022-01879-z">often time-consuming</a> and <a href="https://doi.org/10.3389/fsurg.2021.642503">sometimes prohibitive</a>. </p>
<p>Another barrier is the stigma associated with brain surgery for psychiatric illness. The reasons behind this stigma are complicated, and some factors have historical roots. In the early to mid-1900s, destructive, dangerous and <a href="https://nihrecord.nih.gov/2019/11/01/when-faces-made-case-lobotomy">not very effective brain surgeries such as lobotomies</a> were performed routinely for mental illness without regulation, ethical guidelines or regulatory oversight.</p>
<h2>A way forward</h2>
<p>After I worked with Patel for about a year, including trials of six additional medications and ongoing exposure and response prevention therapy, his symptoms remained severe. I recommended he begin the extensive evaluation process for deep brain stimulation surgery.</p>
<p>Three weeks after his surgery, I turned on electrical stimulation, and we began the intensive programming procedure to determine the optimal settings. This process takes several hours a day over the course of several days, with fine-tuning in the following weeks and months. </p>
<p>Patel recalls that early on, during programming, he experienced a roller coaster of feelings, shifting between “giddiness and sadness.” Most individuals experience gradual improvement over the course of six to 12 months. At first, they feel happier and less anxious, and weeks to months later they experience a decrease in OCD symptoms. </p>
<p>Most commonly, stimulation is constant, 24 hours a day. But the treating psychiatrist may give the patient the ability to turn it off, such as at night if the stimulation causes problems with sleep.</p>
<p>Since surgery, Patel has continued weekly therapy sessions. Research shows that <a href="https://doi.org/10.1017/s0033291714000956">deep brain stimulation is most effective</a> when people continue to engage in exposure and response prevention therapy. Electricity alone will not break years of hard-wired habits, but it can be the catalyst that allows for new neural pathways to be established and new behaviors to be learned. Likewise, most individuals need to continue medication. Though the effects of deep brain stimulation can be remarkable, it is not a cure. </p>
<p>Patel has experienced a 54% reduction in his OCD, according to the <a href="https://doi.org/10.1001/archpsyc.1989.01810110048007">standardized scale</a>. This means that his symptoms decreased from the “extreme OCD” to the “moderate” range. </p>
<p>He can now eat and drink at work and use public restrooms. He has more social connections, seeks less reassurance and spends less time decontaminating himself and his belongings. While sleep was previously his only respite, Patel is now intentional about finding meaningful activities to fill the hours that are no longer occupied by rituals. </p>
<p>Most importantly, he is beginning to feel hopeful that it just might be possible to build a life driven by purpose and intention, rather than by fear.</p><img src="https://counter.theconversation.com/content/186109/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rachel Davis consults for Medtronic, Inc. She receives funding from the NIH . </span></em></p>This rare procedure is offered by only a handful of centers in the US and around the world and should be used only when less invasive treatment options for OCD have been tried.Rachel A. Davis, Associate Professor of Psychiatry and Neurosurgery, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1909502022-09-22T18:08:48Z2022-09-22T18:08:48ZKetamine paired with looking at smiling faces to build positive associations holds promise for helping people with treatment-resistant depression<figure><img src="https://images.theconversation.com/files/485716/original/file-20220920-14233-xe0rz7.jpg?ixlib=rb-1.1.0&rect=10%2C0%2C6699%2C4476&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some of the positive photos used in the study were similar to this one -- a group of smiling strangers.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/successful-business-team-taking-selfie-royalty-free-image/1132119295?adppopup=true">Luis Alvarez/DigitalVision via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Simple computer exercises using positive words and images designed to boost self-worth can prolong the antidepressant effects of ketamine in people with depression. That’s what my research team and I found <a href="https://www.doi.org/10.1176/appi.ajp.20220216">in our new study</a>.</p>
<p>Over two decades ago, researchers serendipitously discovered that intravenous ketamine, a widely used anesthetic medication that has been <a href="https://doi.org/10.1111/j.1365-2044.2007.05298.x">shown to be safe</a> when administered under medical supervision, had <a href="https://doi.org/10.1016/s0006-3223(99)00230-9">rapid-acting antidepressant effects</a> when given at lower doses than is used for anesthesia. </p>
<p>Our study included 154 adult patients with depression. One-third received a single infusion of ketamine and returned a day later to begin four consecutive days – about 30 to 40 minutes total each day – of our novel digital exercises. That is, we showed them repeated pairings of self-related words and images – such as the letter “I” and photos of the patient – paired up repeatedly with positive cues. These include positive words like “good,” “sweet” and “lovable” as well as photos of strangers smiling.</p>
<p>We targeted this period of time within five days of ketamine because we expected ketamine would quickly help restore the brain’s healthy capacity to adjust and learn in response to the environment. The specific exercises we used were designed based on our prior work showing that, shortly after a ketamine infusion, thought patterns related to oneself <a href="https://doi.org/10.1002/da.22253">may become less “stuck”</a> and be more malleable, creating a window of opportunity to improve a person’s sense of self-worth.</p>
<p>The other two-thirds of patients went into one of our two control groups: those who received ketamine followed by a neutral, or placebo, version of computer training, and those who received a saline infusion followed by the real training exercises. </p>
<p>We found that after just a single intravenous infusion of ketamine, patients experienced relief from depression symptoms for at least one month as long as they were assigned to the group that completed the digital exercises within the first five days. Compared with those in the control saline group, both of the groups that received a ketamine infusion experienced substantial relief from depression on the first day, prior to any computer training. </p>
<p>However, whereas the control group who went on to receive the “sham” computer training began to experience the return of depression symptoms in the subsequent 1.5 weeks or so, the group that received ketamine followed by exposure to positive conditioning continued to report decreased depression severity all the way out to the last follow-up interview, one month after ketamine. </p>
<p>The people who got digital training in the absence of ketamine had very little relief from their depression.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/a1Y1ocyudjs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">More than 20 million U.S. adults and 4 million adolescents have had at least one major depressive episode, according to the National Institute of Mental Health.</span></figcaption>
</figure>
<h2>Why it matters</h2>
<p>Depression is a highly prevalent and disabling condition that exacts a staggering burden on patients, families and communities. </p>
<p>Globally, <a href="https://www.who.int/news-room/fact-sheets/detail/depression">an estimated 280 million people</a> experience depression. There are <a href="https://doi.org/10.7326/AITC202105180">numerous effective treatments</a> for depression, including <a href="https://www.nice.org.uk/guidance/ng222">antidepressant medications and psychotherapy</a>. </p>
<p>However, unfortunately, not all patients <a href="https://doi.org/10.1176/ajp.2006.163.11.1905">are helped by such treatments</a>. And accessing them initially, as well as maintaining them over the long haul can be challenging for many patients.</p>
<p>The discovery of ketamine’s rapid-acting antidepressant effects opened up a brand new possibility within psychiatry to begin relieving symptoms within a day. Conventional treatments typically take six to eight weeks to reach a therapeutic effect.</p>
<p>However, a key question is how to keep that relief going without relying solely on repeated ketamine infusions. These can be burdensome and costly for patients and health care systems, and it is important to consider <a href="https://doi.org/10.1176/appi.ajp.2014.13101434">possible risks</a>, such as the potential for drug misuse. </p>
<p>Our study is the first to demonstrate that the rapid effects of ketamine can be made more enduring with simple, portable and automated techniques that would be relatively easy to provide to patients in a wide range of settings. </p>
<h2>What’s next</h2>
<p>Our initial findings suggest the positive conditioning exercises tripled – at a minimum – the duration of ketamine’s effects. But we don’t yet know how much longer the relief from depressive symptoms may have continued. </p>
<p>Patients in our trial will continue to complete questionnaires about their depression symptoms for an entire year following the infusion, enabling us to gain an initial understanding of just how long this benefit may endure.</p>
<p>Ongoing research is exploring whether <a href="https://clinicaltrials.gov/ct2/show/NCT04578938">similar techniques might help ease suicidality</a>, in the hopes of providing relief in the midst of a suicidal crisis that is both immediate and enduring. Other future research may expand these techniques to additional common forms of psychological suffering, such as anxiety, disordered eating and more.</p><img src="https://counter.theconversation.com/content/190950/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Price receives funding from the National Institute of Mental Health.
Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report.</span></em></p>In a new study, a single infusion of the antidepressant – along with repeated exposure to positive imagery – significantly reduced symptoms in depressed patients in a clinical trial.Rebecca Price, Associate Professor of Psychiatry and Psychology, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1889212022-08-23T16:11:22Z2022-08-23T16:11:22ZChemical imbalance theory of depression: clearing up some misconceptions<figure><img src="https://images.theconversation.com/files/480549/original/file-20220823-17-2jwz2h.jpg?ixlib=rb-1.1.0&rect=16%2C8%2C5590%2C3724&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-woman-takes-white-round-pill-634905689">fizkes/Shutterstock</a></span></figcaption></figure><p>The scale of the response to our recent <a href="https://www.nature.com/articles/s41380-022-01661-0">study</a> finding that there was no support for the idea that low serotonin causes depression – the so-called “chemical imbalance” theory of depression – was enormous. Our paper is one of the <a href="https://www.altmetric.com/details/132834624?src=bookmarklet#score">400 most shared</a> of the 21 million papers that have ever been tracked. And our article in The Conversation was read by <a href="https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672">more than 1.3 million people</a>. However, we feel that some of the responses missed the point, and we’d like to address those points here.</p>
<p>The main response from leading psychiatrists was that <a href="https://theconversation.com/depression-low-serotonin-may-not-be-the-cause-but-antidepressants-still-work-187477">antidepressants work</a> and <a href="https://theconversation.com/the-chemical-imbalance-theory-of-depression-is-dead-but-that-doesnt-mean-antidepressants-dont-work-187769">it does not matter how</a>. However, whether antidepressants work is not clear-cut, and how they produce their effects matters.</p>
<p>But first, we want to highlight a point skipped over by many commentators: for decades, people, including doctors, have been misled by false claims about what antidepressants are doing. The marketing line that antidepressants correct an underlying chemical imbalance has <a href="https://pubmed.ncbi.nlm.nih.gov/24657311/">influenced people’s choices</a> about <a href="https://slate.com/technology/2022/08/ssris-chemical-imbalance-depression.html">their treatment</a>, their self-perception, and their outlook <a href="https://pubmed.ncbi.nlm.nih.gov/24657311/">on recovery</a>. </p>
<p>We should acknowledge that people were misled and take stock of how corporate interests and marketing have affected medical discussions, otherwise we will be condemned to repeat these mistakes with new pharmaceutical products. For example, various unsubstantiated theories are currently circulating about how <a href="https://www.psychiatrictimes.com/view/esketamine-depressions-journey-monoamines-glutamate">esketamine</a> might rectify other <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205453/">chemical imbalances</a> or other <a href="https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression#:%7E:text=Esketamine%20Helps%20the%20Brain%20Form%20New%20Connections&text=Studies%20show%20that%20people%20with,the%20harmful%20effects%20of%20depression.">brain abnormalities</a>.</p>
<p>Many people taking antidepressants get better, but whether they work or not <a href="https://www.cambridge.org/core/journals/bjpsych-bulletin/article/against-the-stream-antidepressants-are-not-antidepressants-an-alternative-approach-to-drug-action-and-implications-for-the-use-of-antidepressants/576198D6AEA703B318251B38B2FAE43E">is contested</a>. The evidence for antidepressants’ effectiveness comes from randomised trials that show that people improve when they are given an antidepressant or a placebo.</p>
<p>On average, antidepressants reduce depression scores slightly more than a placebo. But the difference is small: two points on a 52-point depression scale. Evidence from <a href="https://pubmed.ncbi.nlm.nih.gov/23357658/">large analyses</a> of patient responses and National Institute of Health and Care Excellence <a href="https://www.nice.org.uk/guidance/ng222/evidence/b-treatment-of-a-new-episode-of-depression-pdf-11131004415">guideline committees</a> suggests that this is not a big enough difference to be noticeable by patients or doctors. </p>
<p>Even this difference may be exaggerated because antidepressants cause side-effects and other more subtle changes that let people know they are taking the active drug rather than the placebo, which may lead to <a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00407/full">amplified placebo effects</a>.</p>
<p>Furthermore, the studies of antidepressants last for six to eight weeks and <a href="https://bmjopen.bmj.com/content/9/6/e024886">cannot provide evidence</a> of whether taking antidepressants for longer periods is worthwhile, especially the months and years that many people take them for.</p>
<p>But even if we accept that the small difference between antidepressants and placebo is a real effect of the drug, there is no reason to assume, as many experts do, that it reflects the action of antidepressants on some underlying biological mechanism of depression. </p>
<h2>Possible explanations for antidepressants small effect</h2>
<p>First, although brain biology is involved in everything we think and feel, there are <a href="https://www.nature.com/articles/s41380-019-0585-z">no established specific biological causes</a> of depression. Other proposed ways in which antidepressants might target underlying mechanisms are hypotheses, often drawn from animal studies or cells in a dish and none have been consistently demonstrated in humans.</p>
<p>Second, there is <a href="https://www.bmj.com/content/338/bmj.b1963">another explanation</a> for what antidepressants do. Antidepressants are drugs that change brain chemistry, and like other drugs that do this, they produce changes in our mental states and experiences. These changes can temporarily override our current feelings. </p>
<p>For example, alcohol has sedative and relaxing effects that can reduce anxiety and briefly “drown your sorrows”, but this is not because alcohol works on the underlying mechanisms of anxiety or depression. Alcohol’s effects (with individual variation) are experienced by everyone and not just people with one of these diagnoses.</p>
<figure class="align-center ">
<img alt="Man pouring a large glass of whisky." src="https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/480557/original/file-20220823-27-7dwi3y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">You change your brain chemistry with alcohol. That doesn’t make it an antidepressant.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/elegant-man-suffering-alcoholism-drinking-whisky-167097482">Photographee.eu/Shutterstock</a></span>
</figcaption>
</figure>
<p>Antidepressants do not commonly make people merry like alcohol can. They cause a variety of more or less subtle mental alterations, depending on the chemistry of the drug. One common, <a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2021.792960/full">dose-dependent</a> alteration, is <a href="https://pubmed.ncbi.nlm.nih.gov/24534123/">numbing</a> <a href="https://www.sciencedirect.com/science/article/abs/pii/S0165032717308303?via%3Dihub">of emotions</a>. </p>
<p>This effect could also explain why antidepressants perform a little better than placebo in randomised trials. In the short term, the numbing may make people feel less depressed, but in the long term, the benefits are less clear.</p>
<p>This is why drawing analogies between antidepressants and paracetamol – as one <a href="https://www.theguardian.com/society/2022/jul/20/scientists-question-widespread-use-of-antidepressants-after-survey-on-serotonin">commentator has done</a> – is misleading. Paracetamol does not produce significant mental changes, and hence these cannot account for its effects on pain. </p>
<p>Unlike depression, we know there are specific biological mechanisms that produce pain, and we can therefore conclude that paracetamol is working through modifying these, even if we do not know exactly how it does so.</p>
<p>The mechanism of action of antidepressants is crucially important for considering the pros and cons of taking them, especially in the long term, given that we only have short-term trial data. </p>
<p>The idea that antidepressants correct an underlying chemical or other problem in the brain is reassuring – we do not have concerns about the long term use of insulin in diabetics. But if antidepressants are changing brain chemistry, without evidence they are rectifying anything, this is a different situation. </p>
<p>Other drugs that affect the way we feel and think by altering brain chemistry, such as alcohol and other recreational drugs, can cause concentration problems, sleep disturbance and withdrawal symptoms when they are used for long periods – <a href="http://www.eurekaselect.com/article/90929">all of</a> <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2009.02085.x">which</a> are <a href="https://pubmed.ncbi.nlm.nih.gov/30292574/">concerns</a> for antidepressants.</p>
<p>Lastly, we know more about what causes depression than is often thought. The number of stressors in life – job loss, relationship breakdown, physical illness – <a href="https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.161.4.631">strongly predicts</a> who will become depressed. </p>
<p>An over-emphasis on looking for the chemical equation of depression may have distracted us from its social causes and solutions. We suggest that looking for depression in the brain may be similar to opening up the back of our computer when a piece of software crashes: we are making a category error and mistaking problems of the mind for problems in the brain.</p>
<p>It would be wise to observe caution with drugs whose effectiveness is not certain, whose mode of action is unknown, and which have many side-effects, especially for use in the long term.</p><img src="https://counter.theconversation.com/content/188921/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Horowitz is a Collaborating Investigator on the RELEASE trial in Australia investigating supported, gradual, hyperbolic tapering of antidepressants. He is member of the Critical Psychiatry Network and an Associate of the International Institute for Psychiatric Drug Withdrawal (IIPDW). He is a co-founder of Outro Health which aims to use digital support to help people who wish to stop long-term antidepressant medication in Canada and the US using gradual, hyperbolic tapering.
</span></em></p><p class="fine-print"><em><span>Joanna Moncrieff is a co-investigator on a National Institute of Health Research funded study exploring methods of antidepressant discontinuation. She is co-chair person of the Critical Psychiatry Network, an informal and unfunded group of psychiatrists and an unpaid board member of the voluntary group, the Council for Evidence-based Psychiatry.</span></em></p>The authors of one of the most shared research papers in modern history clear up some of the misunderstandings that followed in the wake of its publication.Mark Horowitz, Clinical Research Fellow in Psychiatry, UCLJoanna Moncrieff, Professor of Critical and Social Psychiatry, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1877692022-08-02T06:47:22Z2022-08-02T06:47:22ZThe chemical imbalance theory of depression is dead, but that doesn’t mean antidepressants don’t work<figure><img src="https://images.theconversation.com/files/477102/original/file-20220802-11-orrm1p.jpg?ixlib=rb-1.1.0&rect=24%2C24%2C5439%2C3612&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The chemical imbalance theory of depression is well and truly dead. A <a href="https://www.nature.com/articles/s41380-022-01661-0">paper</a> by Joanna Moncrieff and colleagues, <a href="https://www.ucl.ac.uk/news/2008/mar/myth-chemical-cure-critique-psychiatric-drug-treatment">long-time critics</a> of the effectiveness of antidepressants, has caused a splash. The paper provides a summary of other summaries that confirm there is no evidence to support the idea that depression is caused by disturbance of the brain’s serotonin system. </p>
<p>They have done us a favour by corralling the evidence that says as much, even if we already knew this to be the case. </p>
<p>But the death of the chemical imbalance theory has no bearing on whether antidepressants that affect the serotonin system are effective. These medications weren’t developed on this premise. In fact quite the opposite is true – the chemical imbalance theory was based on an emerging understanding of how antidepressants were shown to work.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672">Depression is probably not caused by a chemical imbalance in the brain – new study</a>
</strong>
</em>
</p>
<hr>
<h2>How did the ‘chemical imbalance’ theory start?</h2>
<p>The first two antidepressant medications, both discovered in the 1950s, were observed to have positive effects on mood as side effects of their hoped-for functions. Iproniazid was developed as a treatment for tubercolosis, and imipramine as an antihistamine. </p>
<p>We know now that ipronizaid is a <a href="https://www.mayoclinic.org/diseases-conditions/depression/in-depth/maois/art-20043992">monoamine oxidase inhibitor</a> – it stops the enzyme that breaks down serotonin and similar brain chemicals. But we didn’t know this when its antidepressant effects were first observed in 1952.</p>
<p>Imipramine is a <a href="https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046983">tricyclic antidepressant</a> and, among other effects, it blocks the reuptake of serotonin after it has been secreted, also allowing more to stay in the brain. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Woman on floor with dog" src="https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477104/original/file-20220802-26-lct4bv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mechanism of action of antidepressants came before the chemical imbalance theory, not the other way around.</span>
<span class="attribution"><span class="source">Shane/Unsplash</span></span>
</figcaption>
</figure>
<p>A simple hypothesis then presented itself: if both classes of antidepressants were shown to increase brain levels of serotonin, then depression must be caused by low levels of serotonin. </p>
<p>Researchers set out to demonstrate this in patients with depression, showing that serotonin and its metabolites and precursors were lower in the <a href="https://pubmed.ncbi.nlm.nih.gov/4123618/">blood</a>, in the <a href="https://pubmed.ncbi.nlm.nih.gov/5962034/">cerebrospinal fluid</a>, and so on.</p>
<p>But these studies suffered from what we now know plagued many studies of their era, leading to the so-called “<a href="https://www.vox.com/future-perfect/21504366/science-replication-crisis-peer-review-statistics">replication crisis</a>”. Studies used small sample sizes, selectively reported their results, and if they failed to demonstrate the hypothesis, were often not reported at all. In short, the findings were unreliable, and since then larger studies and meta-analyses (which summarised the many smaller studies), made it clear the hypothesis wasn’t supported.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-depression-11447">Explainer: what is depression?</a>
</strong>
</em>
</p>
<hr>
<h2>What’s the link between the theory and antidepressants?</h2>
<p>In the meantime, pharmaceutical companies spotted a clear line to communicate the effectiveness of their medications. Depression was caused by a “chemical imbalance” that could be corrected by antidepressants. </p>
<p>This coincided with the development of a new class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), which, as their name suggests, were more selective than the tricyclic antidepressants in targeting serotonin reuptake as their mechanism of action. </p>
<p>These drugs – then known as Prozac, Zoloft, and Cipramil – became blockbusters, and remain widely used today (albeit with a variety of names since expiration of their patents).</p>
<p>Few psychiatrists with an understanding of the nuance of brain function believed the chemical imbalance theory. It never fitted with the way they could see that SSRIs worked, with serotonin function changing hours after taking the medication, but depression not showing improvement for about four weeks. </p>
<p>But there were, and are, many medical practitioners with less sophisticated understanding of depression and neurochemistry who were happy to repeat this message to their patients. It was an effective message, and one that took hold in the popular imagination. I have heard it repeated many times.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pills in shape of happy and sad faces" src="https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477106/original/file-20220802-22-xdtl9v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">SSRIs don’t work for everyone.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>So are antidepressants effective?</h2>
<p>The new paper by Moncrieff and colleagues, while not saying anything new, does us all a favour by reiterating the message that has been clear for some time: there is no evidence to support the chemical imbalance theory. Their message has been amplified by the extensive media attention the article has received. </p>
<p>But much of the commentary has extrapolated from the study’s finding to suggest it undermines the effectiveness of antidepressants – including by the <a href="https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672">authors</a> themselves.</p>
<p>This shows a misunderstanding of how medical science works. Medicine is pragmatic. Medicine has often established that a treatment works well before it has understood how it works.</p>
<p>Many commonly used medicines were used for decades before we understood their mechanisms of action: from aspirin to morphine to penicillin. Knowing they worked provided the impetus for establishing how they worked; and this knowledge generated new treatments.</p>
<p>The evidence for <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext">SSRIs being effective</a> for depression is convincing to most reasonable assessors. They are not effective for as many people with depression as we might hope, as I have <a href="https://www.mja.com.au/journal/2016/204/9/unfulfilled-promise-antidepressant-medications">written</a> before, but they are, overall, more effective than placebo treatments.</p>
<p>Critics suggest the magnitude of the difference between the medications and placebo isn’t great enough to warrant their use. That is a matter of opinion. And many people report very significant benefits, even as some people report none, or even that they have caused harm.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-causes-depression-what-we-know-dont-know-and-suspect-81483">What causes depression? What we know, don’t know and suspect</a>
</strong>
</em>
</p>
<hr>
<h2>If it’s not a chemical imbalance, how do antidepressants work?</h2>
<p>In truth, we still don’t really know how or why antidepressants work. The brain is a complex organ. We still don’t have a clear idea about how <a href="https://www.sciencealert.com/for-over-150-years-how-general-anaesthesia-works-has-eluded-scientists-we-re-finally-getting-close">general anaesthetics work</a>. But few people would refuse an anaesthetic when contemplating serious surgery on this basis. </p>
<p>In the same vein, when contemplating whether an antidepressant might be an option for someone with depression, it is of little consequence that its mechanism of action is incompletely understood.</p>
<p>So let’s put the chemical imbalance theory to bed. We should continue our efforts to understand the nature of depression, while we keep searching for better treatments.</p>
<p>Attending to diet, exercise, and sleep is effective for many people with depression. Psychotherapy can be very helpful too. But many people struggle with depression despite trying these things, and it is for them that we need to keep up our efforts to find better treatments.</p><img src="https://counter.theconversation.com/content/187769/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Davey does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A recent review of studies concluded depression is not caused by a lack of serotonin in the brain. But this doesn’t mean antidepressants, which work on serotonin, aren’t effective.Christopher Davey, Head of the Department of Psychiatry, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1782622022-07-29T12:20:56Z2022-07-29T12:20:56ZTaking certain opioids while on commonly prescribed antidepressants may increase the risk of overdose<figure><img src="https://images.theconversation.com/files/476389/original/file-20220727-1345-spk5fx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2127%2C1407&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Certain SSRIs can inhibit the breakdown of opioids in the body.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/hands-of-man-in-robe-surrounded-by-prescription-royalty-free-image/588316210">Glasshouse Images/The Image Bank via Getty Images</a></span></figcaption></figure><p>Taking oxycodone at the same time as certain selective serotonin reuptake inhibitors (SSRIs), a commonly prescribed class of antidepressant, can <a href="https://doi.org/10.1001/jamanetworkopen.2022.0194">increase the risk of opioid overdose</a>, according to a study my colleagues <a href="https://scholar.google.com/citations?user=nqtrb3oAAAAJ&hl=en">and I</a> published.</p>
<p>Doctors prescribe the opioid <a href="https://www.cdc.gov/opioids/basics/prescribed.html">oxycodone</a> to treat moderate to severe pain after surgeries and injuries or certain conditions like cancer. Opioids are also a <a href="https://www.cdc.gov/drugoverdose/epidemic/index.html">common drug of abuse</a>. In the U.S., over 70% of drug overdose deaths in 2019 involved an opioid. </p>
<p>Because many patients with depression <a href="https://doi.org/10.1001/archinte.163.20.2433">also experience chronic pain</a>, opioids are often <a href="https://doi.org/10.18773/austprescr.2021.004">coprescribed with antidepressants</a> like SSRIs. <a href="http://dx.doi.org/10.2174/1389200023338017">Prior research</a> has shown that certain SSRIs, namely fluoxetine (Prozac or Sarafem) and paroxetine (Paxil, Pexeva or Brisdelle), can strongly inhibit a liver enzyme crucial to the proper breakdown of drugs in the body, including oxycodone. The resulting increased concentration of oxycodone in the blood may lead to accidental overdose.</p>
<p>To see whether different types of SSRIs might affect a patient’s risk of overdosing on oxycodone, my colleagues and I examined data from three large U.S. health insurance claims databases. We included over 2 million adults who began taking oxycodone while using SSRIs between 2000 and 2020. The average age of the group was around 50, and a little over 72% were women. A little over 30% were taking the SSRIs paroxetine and fluoxetine.</p>
<p>We found that patients taking paroxetine or fluoxetine had a 23% higher risk of overdosing on oxycodone than those using other SSRIs.</p>
<p><a href="https://doi.org/10.7556/jaoa.2019.136">About 30% of patients</a> with chronic pain experience adverse drug interactions while taking opioids. Other types of drugs have been shown to increase the risk of overdose and other harmful interactions. These include some <a href="https://doi.org/10.1002/cpt.1807">muscle relaxants</a> commonly used to treat pain, <a href="https://doi.org/10.1001/jamanetworkopen.2018.0919">benzodiazepines</a> commonly used to treat anxiety or poor sleep and some <a href="https://doi.org/10.1093/schbul/sbab116">antipsychotics</a> commonly used to treat schizophrenia or bipolar disorder. Similarly, in 2019, the Food and Drug Administration required drugmakers to <a href="https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings-gabapentinoids-about-risk-respiratory-depression">include new warnings</a> on using gabapentinoids, a class of drugs commonly used to treat epilepsy and pain, concurrently with opioids and other drugs that suppress the central nervous system. This mandate was due to an increased risk of <a href="https://theconversation.com/pain-and-anxiety-are-linked-to-breathing-in-mouse-brains-suggesting-a-potential-target-to-prevent-opioid-overdose-deaths-174187">dangerously reduced breathing rates</a> that can result in overdose and death when these drugs are taken together.</p>
<p>The findings from our study offer insight on which of the most commonly used antidepressants could most likely lead to opioid overdose. Further investigation of how other drugs interact with opioids could help doctors and patients better understand which drugs are safe to take at the same time.</p><img src="https://counter.theconversation.com/content/178262/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ismaeel Yunusa does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Drugs can interact with one another in ways that are harmful. A study finds that taking oxycodone with certain SSRIs can make an opioid overdose more likely.Ismaeel Yunusa, Assistant Professor of Clinical Pharmacy and Outcomes Sciences, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.