12 August 2015

Could some acne medications cause depression and suicide?

CyberShrink discusses the side-effects of Accutane, a very effective acne medication, one of which appears to be severe depression.


Of course we want acne drugs and treatments to be both effective and safe, but somehow this is easier said than done. 

Dangerous side-effects

Recently, on the CyberShrink Forum, a mother reported that her daughter had developed severe anxiety, depression and suicidal thoughts after a few weeks on Accutane (used to treat severe acne), and still hadn’t recovered after four months of treatment. (This article is about the drug Isotretinoin, which will be referred to as Accutane [formerly Roccutane], the name under which it is sold in South Africa.)

The question about the dangerous side-effects of Accutane remains annoyingly unsettled. We may hear stories from friends about horrible side-effects, but doctors are often strangely reluctant to discuss important facts about any of the drugs they prescribe and don’t explain possible side-effects.

Read: Computer can predict drug side effects

There is however no good excuse for them not to do so. Some doctors have explained that they believe that if they mention side-effects, the person will inevitably experience them. This is superstition, not fact.  Not only is there no evidence that this actually happens, but research actually shows that people who’ve been given a proper explanation of benefits and risks, are no more likely to experience side-effects – and if they do, they’re more likely to remain on the drug and benefit from it. 

Since Accutane was first released in America in 1982, there have been repeated reports of serious problems like birth defects, suicidal depression, and bowel disorders. The parent company, Roche, stopped making it in 2009, not because of safety issues, but because the exclusive patent had lapsed and it was no longer guaranteed to be a profitable product, even though it remained very expensive. It has remained available in generic versions.

Usually drug companies try very hard to find creative ways to extend their patent rights to any profitable drug and discourage the advent of generics. Roche did not choose to do so in this case, perhaps because there are reports of close to 1,000 lawsuits against the company, with many more pending. Such litigation is expensive – with a potential for punitive damages and compensation.    

Dermatologists had been delighted to have a treatment that could produce dramatic improvements in chronic severe acne that was not responding to routine treatments. Indeed, in many cases the condition was described as cured, an uncommon outcome in medicine. South African guidelines for its use, written by dermatologists, are highly enthusiastic, warning only of “foetal damage”, and describing other side-effects as “uncomfortable rather than dangerous”. 

Permanent facial scarring and disfigurement

But over the past 30 years thousands of patients across the world have complained of serious side-effects. 

Accutane is only supposed to be used in severe nodular acne when there are large, painful red lumps on the skin, potentially causing permanent facial scarring and disfigurement, which can lead to psychological distress and severe depression.

That Accutane can cause serious birth defects when taken by pregnant women is a fact, and great care needs to be taken by the prescribing doctor to make sure that the woman is not pregnant, and is using effective contraception to avoid pregnancy during treatment. In a 2007 study of 90 women who became pregnant while taking Accutane (isotretinoin), only 9 had a live birth and 76 had elective abortions. Obviously this is unacceptable, and care to avoid pregnancy is paramount.

Read: Abortion: religion plays small role

Researchers in gastroenterology have indicated that shown that Accutane users have a higher incidence of various digestive disorders (about double the usual risk), inflammatory bowel disease (four times the normal risk). Raised cholesterol levels and liver toxicity have also been recorded.

There have been a multitude of reports of severe depression associated with Accutane use. However, it is important to remember that things may be associated in the sense that they often occur together, without one actually causing the other. Whether Accutane actually causes depression is not yet clear.

In 1998 the American FDA (Food and Drug Administration) issued a formal warning to doctors of a possible association between isotretinoin and depression, psychosis, suicidal thinking and suicide. The FDA recommended that patients should sign informed consent forms and receive a printed guide.

The evidence for an association

Between 1982 and 2000, the FDA received 394 reports of cases of depression and 37 suicides in patients taking isotretinoin. Of all drugs reported to the US system for reporting adverse drug effects, it’s the 5th most often reported as associated with depression, and the 10th most often reported with regards to suicide. A similar situation presented itself in Canada, Australia and Britain. 

It’s worth noting that in a number of the reported cases the depression resolved when the person stopped taking the Accutane, and returned when it was started again. 

Read: The depressed child

Such situations can be more complex than they seem. One case appeared very clear: a 17 year-old boy in Korea behaved oddly while taking isotretinoin, improved when it was stopped, and started acting strangely again when it was re-started – and the drug was blamed. Then they discovered he had also been taking street LSD and cannabis at those times.

Another way to study these issues is to analyse very large volumes of information about large numbers of patients, and this has produced different results. Analysis of the Canadian Health Database and the British General Practice Research Database found no increase in the risk of depression, or suicide, attempted or completed, when comparing people with acne treated by Accutane and those treated with antibiotics.

There have been concerns about the fact that that this study was sponsored by the drug industry, and with aspects of the research itself. It ignored the severity of the acne and the doses of the drug, among other flaws.

An actual improvement in depression in some patients

Another large scale study showed no relationship between the drug and depression. But another calculated that if there was no causal effect, there should have been only 6 suicides in those taking Accutane, whereas there were actually 36 reported, thus suggesting it might indeed have caused depression.

On the other hand, because having severe, painful and ugly acne is in itself depressing, some researchers have reported an actual improvement in depression in some patients on Accutane. But remember that the issue isn’t whether everyone who takes the drug becomes severely depressed. The question is whether some people run an increased risk of severe and dangerous depression.

Read: Causes of depression

A chemically similar drug, etretinate, also used for skin disease, has been reported to be associated with depression as well.  Accutane has also been reported to show a range of other possible side-effects suggesting psychiatric/neurological impact: such as irritability, unstable emotions, memory problems, tiredness, incoordination and marked dreaming.   

There is already a significant risk of depression and suicide attempts in adolescents, the very group most likely to need Accutane. Some studies found a greater degree of impairment of mental health due to acne than from asthma, epilepsy, diabetes, pain or arthritis, so this is far from a trivial condition. Acne by itself has been associated with depression and suicide.


So how should we deal with the question about whether and how to use Accutane? As I see it, there is not enough convincing evidence to assume a high risk of depression or suicide, but also not enough evidence of safety to allow us to assume that there is no risk. The risk may not be the same for everyone, and the severe depression and suicidality reported with Accutane use may be a high risk for a small number of people we can’t identify in advance, and a very low or no risk for many others.

There have been a surprising number of studies with really significant flaws, failing to satisfactorily resolve this important question. The lack of enough research to answer the question definitively is not a matter of negligence – to try to do it properly would be very expensive and difficult. Considering how effective the drug is for the severe acne, there would be ethical problems both in administering it to some patients, and in withholding it from others, in such an experiment.

Read: Ethics in health research

As a precaution it would be wise for the drug to be prescribed only by specialists such as dermatologists after screening for existing depression, and obtaining a psychiatric opinion where this is present. It should be reserved for really severe cases and not be used for mild acne.

Patients and their families should be informed that there is a risk of depression so that they can be vigilant. (They should also be informed of other potential risks and benefits.)

There appears to be no evidence suggesting that Accutane has any effect on the standard treatments for depression.

Read more:

Acne linked to thoughts of suicide

Symptoms of acne

Overweight teen girls have higher acne risk

Reference: Isotretinoin, depression and suicide: a review of the evidence. Magin & Smith. Br J Gen Pract. 2005 Feb 1; 55(511): 134–138.

Image: Depressed teenager from Shutteerstock

Professor MA Simpson is Health24's CyberShrink. A South African psychiatrist, he qualified in medicine and in psychiatry in Britain. He has been a senior academic, researcher, and Professor in several countries. Read more of his columns.


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Michael Simpson has been a senior psychiatric academic, researcher, and Professor in several countries, having worked at London University in the UK; McMaster University in Canada; Temple University in Philadelphia, USA.; and the University of Natal in South Africa.

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