Old made new: medication offers hope for bipolar depression

Current treatments for bipolar disorder are more effective for the symptoms of mania than for depression. Chris Connelly

Little understood and lacking effective drugs for addressing the scope of its symptoms, bipolar disorder can wreak havoc with the lives of people who suffer from it.

Now an over-the-counter drug is offering hope for treating the sometimes deadly depressive stage of this disorder.

Bipolar disorder affects approximately 1% to 2% of the population and is characterized by two illness phases – mania and depression.

The symptoms of mania include increased energy, decreased sleep, enhanced impulsivity and elevated mood while the symptoms of depression include decreased mood and energy, altered sleep patterns, suicidal thoughts and a lack of motivation.

People with bipolar disorder tend to spend more time in the depressive phase than the manic phase. And suicide, the most catastrophic consequence of the disorder, is more of a risk during depression.

Current treatments for bipolar disorder are more effective for the symptoms of mania than for depression.

What’s more, standard medications used to treat unipolar (clinical) depression aren’t as effective for treating the depressive phase of bipolar disorder (commonly known as bipolar depression).

Little known

We don’t know the precise mechanisms that lead to bipolar disorder but there’s consensus among the research community that it involves complex interactions of many factors.

One of the few things we do know is that people with bipolar disorder have increased oxidative stress.

Oxidative stress is a state in which the brain’s capacity to defend against free radicals is overwhelmed, leading to cell damage and adverse changes in the way cells function.

Examples of oxidation in action are rusting iron, or when your apple turns brown once you’ve bitten it. The brown part of the apple is damaged by oxidative stress.

During normal brain function, free radicals are produced and have healthy functions in the brain’s biological systems. The balance between oxidative stress and oxidative defences is maintained by antioxidants.

It is only when the levels of free radicals exceed the levels of antioxidants that oxidative stress occurs. This may occur both through increased oxidative stress or a decrease in antioxidant capacity.

It appears that both of these factors are present in bipolar disorder.

A promising find

Cysteine is an essential amino acid required for many biological functions. It’s the critical component of the brain’s primary antioxidant, glutathione.

N-acetyl cysteine (NAC) – a registered medicine currently used to treat paracetamol overdose and as a mucolytic (breaks down phlegm) in cystic fibrosis – is a modified version of this naturally occurring amino acid.

Having previously shown that NAC reduces the core symptoms of bipolar disorder and schizophrenia, our research team is now studying NAC for the treatment of unipolar (clinical) depression and autism.

In our latest study, we investigated the potential benefits of N-acetyl cysteine as an adjunctive (or add-on) treatment for bipolar depression.

Given the increased oxidative stress in bipolar disorder, we studied NAC to see if increasing the levels of the primary antioxidant in the brain (glutathione) could improve the symptoms experienced by those with the disorder. (Remember that people with bipolar disorder have decreased defenses against oxidative stress.)

The study involved 149 people (aged between 22 and 70 years) with bipolar depression who were recruited across several sites including Melbourne, Geelong, Sydney and Brazil.

All of the participants in the study received 2 grams of NAC a day for two months, in addition to any medication they were already taking.

This “add-on” design is more attractive to participants as they can continue with their current treatment. It also more closely reflects reality, as people with bipolar disorder are often given combinations of treatments.

We found that participants’ depressive symptoms decreased significantly over the two-month period. And overall, participants reported improved functioning (such as increased rates of work or better social interactions) and quality of life.

This suggests NAC may be effective as an add-on therapy for the treatment of bipolar disorder.

And unlike what happens in many clinical trials, NAC was available for purchase at the end of the study. N-acetyl cysteine can be purchased from a limited number of pharmacies in Australia and is also available from online sources.

Further studies are required to fully explore the potential of NAC as a treatment for bipolar depression even though these results are promising.

The impact of bipolar disorder can be significant and while current therapies are useful, many people either don’t respond or tolerate treatment.

Studies such as these provide hope for newer and safer therapies that may lead to better outcomes for people with the disorder.

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