Insomnia is far from a modern concept, with sleep remedies such as opioids, chamomile and valerian root recorded in the earliest existing medical writings. The word insomnia itself dates back to at least the 1620s.
But since the latter part of the twentieth century our sleep woes have worsened. Increasing economic prosperity and consumerism have increased work hours and led to more unpredictable shift work. And the widespread use of electric lights and caffeine keep us awake longer and longer.
Most doctors promote non-drug techniques such as sleep hygiene and cognitive-behavioural strategies before resorting to medication. But while techniques can be highly effective, they take time and effort to succeed, and they’re incredibly difficult to explain in a ten-minute GP consultation.
So how effective are prescription drugs at getting us to sleep on demand? And what risks do they come with?
Benzodiazepines
The most commonly prescribed sleeping tablets in Australia are benzodiazepines (BZDs). Temazepam (known under brand names Normison, Temaze, TemTabs, Euhypnos) is a short-acting BZD, which means that within six hours it has had its effect and been excreted from the body. Other BZDs used for insomnia with slightly longer actions times include oxazepam (brand names Alepam, Murelax, Serepax), nitrazepam (Alodorm, Mogadon) and diazepam (Antenex, Valium).
Despite their unsavoury reputation as “date-rape drugs” and drugs of addiction, BZDs have a recognisable role in medical practice for treating a handful of sleep disorders and as part of the treatment of severe anxiety disorders. They’re also used to manage agitation, alcohol withdrawal and acute situational crisis episodes.
But given the limited number of generally accepted scenarios for prescribing them, it’s hard to work out why temazepam and diazepam alone were written on around 3.1 million Australian PBS prescriptions in 2010 alone. This doesn’t include oxazepam or alprazolam, which have a limited availability on the PBS.
The sleep-related benefits of BZDs only last couple of months. Longer-term users experience the withdrawal rebound insomnia when they try to skip doses. Users often assume they’ll never be able to sleep without them and may even decide that long-term dependence is preferable to any risk of a withdrawal syndrome.
The BZD withdrawal period is notoriously long and difficult, requiring slow weaning for months to avoid symptoms such as nausea, cravings, headaches, severe anxiety, poor concentration, mood swings and even delirium.
For these reasons, the National Prescribing Service’s guidelines recommend only short-term use.
The pharmacology of BZDs is very complex, but it’s fair to say there can be unpredictable effects that differ from one person to another due to genetic and developmental differences which can’t be foreseen.
Z-drugs
During the 1990s, a newer group of sleep drugs came onto the market. These drugs targeted more specific receptor subtypes on the brain than BZDs, though they worked in much the same way. These drugs have become known as the “Z-drugs” and include zolpidem (Stilnox, Stildem, Somidem) and zopiclone (Imovane, Imrest).
But despite hopes Z-drugs may have had fewer problems and better efficacy than the BZDs, there seems to be little to choose between them.
Zolpidem has been associated with complex automatic behaviours such as sleep-driving, -walking, -eating and other purposeful behaviours. A patient of mine was found cooking pasta at 3am, after having taken Zolpidem and going to sleep. She was in a confused state and had no recollection of the event the next day. Other people have reported writing emails in their sleep.
These kinds of adverse events were being reported in Australia long before the publicity surrounding Heath Ledger’s tragic death brought it to wider public and regulatory awareness in early 2008.
But it’s important to note that these problems aren’t isolated to Z-drugs: similar reactions have been reported with every other sleep drug.
Over-the-counter and herbal products
Despite widespread confidence in valerian plant preparations, there remains little convincing high-level evidence that it improves sleep quality. Some studies have found valerian to have a positive effect, but the lack of agreement in published trials means no clear conclusion can be drawn.
Valerian is believed to act via the same receptor pathway as BZDs and Z-drugs, so it would be reasonable to suspect the longer-term issues of tolerance and poor efficacy would be similar. It can also cause liver toxicity, as can kava, another popular herbal recommendation for insomnia.
Chamomile is the other very commonly recommended sleep herb, but I could only find one fairly decent (though small) trial which was negative.
As for the rest of the complementary medicines, a systematic review published in 2010 gives little cause for optimism.
Melatonin
The one area of mildly positive news is melatonin and its derivatives. Melatonin is a hormone secreted by the pituitary gland and can be produced synthetically. It’s also found in some plants, including cherries.
Melatonin appears to be fairly effective in aiding sleep the short term, and it seems to be free of major side effects.
We have no information on whether it remains effective in the longer term. Melatonin is an important regulatory hormone that contributes to several other processes in the body, so it’s possible there could be unforeseen problems with long-term use.
Some newer melatonin-like molecules may be better suited to the sleep-related functions of melatonin, while having less effect on the other hormonal systems it activates.
A word of warning
We have been struggling with sleep as a species for so long, the use of anything other than very occasional doses of sleep medications – over-the-counter or prescription – needs to be strongly justified by compelling clinical need.
As clinicians, we do not do patients a favour by overseeing the exchange of one set of problems for a whole raft of others they didn’t sign up for. But this may mean giving up on the idea of sleep on demand.
Luke Weston
Physicist / electronic engineer
What are your thoughts on the use of antihistamines to manage insomnia?
They do not seem to have the same risks and dependency potential as BZDs, but they are definitely effective unlike valerian.
After trying valerian, and finding it to have zero discernible effect, and wanting to avoid BZDs unless really necessary, I tried doxylamine and I was frankly surprised because I was not expecting a schedule 3 drug to be such a potently effective sedative.
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Antihistamines often cause drowsiness as a side effect, and I must say I tend to use hyoscine as my sedation on plane flights bc I'm very susceptible to it. Doxylamine is an odd drug which can be very sedating and also can impair cognitive function. It is notoriously prone to causing rebound headaches and insomnia and develops tolerance quite quickly.
Tricyclics are also useful and seem ok for longer term use if you can tolerate them. Pregabalin can also be used long term to improve sleep quality. I was trying to keep the article short an sweet so I concentrated on drugs that basically have no other purpose than getting to sleep.
Sean Lamb
Science Denier
I generally don't have a problem with sleep but I have to alter my sleep patterns regularly and that sometimes can be difficult.
I thought I would try melatonin and asked at the vitamin shop if they had any, they did. It wasn't until I got it home that I read the dreaded words "homeopathic preparation" in the fine print.
I think the theory is that water is supposed to contain the "memory" of the melatonin, but since the pills are solid I suppose I have to hope that the solid matrix contains the memory of the water than had the memory of the melatonin.
Sue Ieraci
Public hospital clinician
Sean - I would suggest that homeopathic melatonin would only give you the "memory" of sleep.
Or perhaps you could heat the tablets, because they are generally made of lactose, and warm milk is a traditional sleep rememdy.
Easy to buy Melatonin in the US, though - sold over the counter.
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Sean
A suitably quality-controlled (ie TGA-R) formulation of melatonin is available on private script. I think that would be more likely to help than the memory of a memory of a trace of melatonin ;)
Peter Reefman
Project Manager
I ALSO tried some Vitamin Shop "Melatonin", and found that the limit of the memory effect was that I DID indeed remember that once I used to sleep well!
I managed to get some proper Melatonin from the USA (ordered over the internet with no problems) and found for MY particular sleep issues that it seemed to have a marginal benefit for a while, sometimes. I have little problem falling asleep, but tend to wake at 3 to 4am. Initially I found I was waking at more like 4:30 to 5am, though a couple of glasses of wine with a late dinner seemed to snuff that out.
Lately, after about a year or so of use I've found that there seems to be no noticeable difference between taking it and not taking it. So I just go to bed before 9pm as often as possible to get a decent amount of sleep. Sadly, my more night-owl oriented wife finds it frustrating that just when she'd like to sit down and have a chat/cuppa/etc I bid her and the family good night!
Tony P Grant
Neo-Mort
I'm finding buying many "script drugs" is getting easier...without a script including DHEA/Melatonin/ED drugs from international sources via the internet...the TGA are a "painful experience"!
Tony P Grant
Neo-Mort
Very cheap, I got 10 bottles for $60 2.5mg x 60 per bottle. Not including freight. The days of paying 3/4 times the price are over.
A Saliva test can confirm if you have a depletion of melatonin and watch for "contraindications" if taking any others meds...from experience...one "bad trip"!
Bruce Moon
Bystander!
Michael
From what you have written, I suggest you have a problem.
Your article is a good overview of the clinicians approach to 'insomnia', except...
As a clinician, you have swallowed the drug company's line that only products tested according to the 'evidence based method' are efficacious.
Being beholden to regulations, drug companies spend large amounts to test and advocate their products.
Products that are not subjected to 'evidence based methods' thus undermine the drug companies…
Read moreStephen Prowse
CEO at Wound CRC
Quote "Despite 'widespread confidence', because it has not been tested according to the 'evidence based methods' used by drug companies, it is therefore not to be endorsed.
This, I suggest is your problem. Are you but an agent for drug companies, or a clinician with an open mind."
How else does one test something except by collecting evidence in a way that can be analysed? It does not matter whether it is big pharma or a small complementary medicine company; they should both have to have some justification for claims of efficacy.
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Thanks for commenting Bruce. You have enormous belief in the ability of the drug companies to influence clinicians. Controlled trials of drugs have been around since they were first suggested by the Arabic physician Ibn Sina (known in Europe by the Latinized form Avicenna) in the Middle Ages. The most recent refinement of doing double-blinded randomized controlled studies to determine efficacy has become accepted as the standard since the 1960s or so. The prinicples that underlie the reliability of these methods are what makes them the gold standard.
You have the cart before the horse with Big Pharma. They do lots of high-quality trials because they know perfectly well that clinicians won't accept anything else as proof of efficacy, not the other way around.
Bruce Moon
Bystander!
Michael
You do a better job than I explaining your problem.
The simple fact is that such blind adherence to clinical trials profits only big pharma (as you describe them).
The idea that ONLY products that are efficacious are those that are shown to be so by controlled trials is folly.
Clinical trials do not invalidate products not the subject of same. Rather, clinical trials validate ONLY those that have undergone same successfully.
To limit your conversation on insomnia solutions to products 'validated' by clinical trials, AND slag off at age old natural remedies because they haven't passed the big pharma test shows a subjective and limited reality.
As an aside, some 30 years ago, western GP's advanced the same approach you are advancing in relation to acupuncture and chiropractic. Consumer acceptance showed them they were wrong - benefits did accrue for some.
Cheers
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Bruce,
The empirical method you describe, whereby 'it works for me' is as good as 'consistently better than placebo' has long been abandoned. I (and most doctors in fact) will happily adopt any treatment which we find convincing. Your contention that we should just go back to empiricism and arguments from authority (such as acupuncture and chiropractic still use) will never happen. That isn't science-based health care being blinkered, it's how we find out more. I forget who it was that said "Confidence and faith makes you eel secure but it's doubt that gets you an education" but I certainly like the quote..
Kenneth Mazzarol
Kenneth Mazzarol is a Friend of The Conversation.
Retired
Why does everyone overlook Vitamin D3 when trying to find a solution to medical problems. There it is, the sun, bursting with free energy we only need to step naked out into it for ten minutes at midday twice a week to gain 20,000IUs at a time. But no! Man, thinking he is God, is manufacturing synthetic stuff which is making us even sicker than we were before. Oh! the power of the mighty dollar!
Jennifer Pilgrim
Postdoctoral researcher in Forensic Toxicology at Monash University
3.1 million prescriptions for diazepam/temazepam in 2010 is a concerning figure- especially considering privately written scripts are not captured in most reported PBS statistics, suggesting this number is a probably an underestimation. As you mentioned, BZPs are indicated for short-term use only, however I’m not sure how often this advice is followed!
I research drugs in sudden death and anecdotal reports from colleagues indicate alprazolam is a widespread and growing problem- have you noticed an increase in alprazolam dependence in recent years?
Since benzodiazepines were first marketed in the 1960s to replace barbiturates and end the self-poisoning ‘epidemic’, they have been seen as almost inherently 'safe' drugs- it seems that benzodiazepines may not be as benign as many once thought!
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Thanks Jennifer,
Alprazolam is a big concern as its rapid onset and potent effect predispose it to being an effective addiction trigger. It also has a fairly short half-life which means that users (whether licit or illicit) are soon feeling like they need more.
My colleagues in addiction medicine tell me that alprazolam is a highly-regarded drug to abuse, and they believe abuse of it is increasing. Exact figures are very hard to get for methodological reasons, and because so many of the scripts are non-PBS.
I agree with your last comment that while they are much safer than barbiturates in overdose, hypnotic drugs are certainly not benign.
Tony P Grant
Neo-Mort
The danger for those that are seeking "mothers' little helpers" sure...
Those where near every day is a struggle...everything assists and often "addiction" is not the primary concern!
Both Michael and Jennifer would be aware of the many "working/walking wounded"?
Peter Gerard
Retired medical practitioner
I don't wish to trivialize this important subject, but the best 'sleeping pill' in my opinion is sexual intercourse or its variations. When depression and over-work is a problem it can be difficult to motivate one's self, but try it.
Tony P Grant
Neo-Mort
If it was that easy doc!
Tom Hennessy
Retired
"Several research studies have confirmed L-tryptophan to be useful in the treatment of chronic insomnia at doses of between one to four grams at bedtime."
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Thanks for pointing out L-tryptophan. As it is a precursor molecule for serotonin (otherwise known as 5-hydroxytryptophan), the idea was that high doses should induce sleep as the tryptophan is metabolized into serotonin, thereby mimicking the natural serotonin rise in the brain that has been hypothesized to be a trigger for sleep. There are some small studies which suggested this might be correct, but larger and better ones (as so often happens) failed to confirm that there was a definite relationship. The article I linked to which reviewed the literature about CAMs and insomnia included L-tryptophan with the comment that evidence was 'mixed'.
Edward John Fearn
Edward John Fearn is a Friend of The Conversation.
Hypnotherapist and Naturopath
Michael
Thank you for the extremely interesting post, I am glad some of the non drug interventions were brought up in this discussion. A number of Hospitals across the country run excellent sleep disorder clinics, those readers with difficulties in this area should speak to their GP about a referral.
I am optimistic that Valerian will be vindicated in future clinical trials; it is a commonly held belief amongst herbalists that the liquid tincture has a stronger effect than tablet form. This…
Read moreMichael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Thanks for your comment Edward
I'm not sure how much I share your optimism about valerian. Not so much because it may be ineffective, but rather because even if it eventually can be shown to be statistically superior to placebo (which wouldn't surprise anybody much) I think it's relatively small clinical effect size and mode of action mean it is essentially like a weak benzodiazepine in terms of tolerance and rebound insomnia. I have quite a few patients who have had pretty typical withdrawal…
Read moreTony P Grant
Neo-Mort
Costs and long term benefits...if you can afford the "pampering of a quality medically trained person and or private hospital time" there are many possible benefits, 5 star service?
When the science is in and peer reviewed papers are in "Science/AMJ et al we will all be very pleased.
Julie Brown
Retired
I cannot remember the last time I went to bed and slept, unmedicated. I have bi-polar, I know doesn't everyone right, with extreme anxiety on occasions so the thought of laying awake, or staying up most of the night really freaks me out. I will take anything and everything to put me to sleep, in between prescription shopping I use Dolased, Mersyndol until the amounts I take are ridiculous then I go back to prescription shopping. I don't like what I am doing, yes I develop tolerances to everything, but the alternative... three nights without sleep, massive depression and delusional is not a trip I want to take. Of course I have tried all the safe options, but if I have to take anti depressants and mood stabilisers in ever increasing amounts to make me fit for society why the hell can't I take a pill or two or three to help me sleep?????????
Michael Vagg
Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health
Thanks for your perspective Julie.
I aim to be morally neutral and nonjudgemental about what can be very emotive issues in this discussion. Mood and sleep patterns are both controlled by the same part of the brain, and therefore sleep is usually the first thing to go in both bipolar disorder and depressive illness. What I have been talking about above is what the research shows.
Decisions about individuals and their care need to be made by careful weighing of the risks of sleeping pills (which are well documented) and the possible benefits (which sound as though they are there in your case). It's a bit like taking cortisone for asthma. It causes lots of well-known adverse effects, but it's often judged to be worth these side effects if it keeps somebody's asthma from putting them in hospital every 2 weeks. A good GP or cimmunity mental health worker to act as a long-term partner in managing the effects of bipolar is essential in keeping things as good as they can be.