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Isotretinoin and suicide

Systematic reviews
Results
New cohort study [3]
Comment

Bandolier, like many of its readers, finds rare associations between an intervention and some rare but serious adverse event both interesting and challenging. It is interesting because any evidence that informs on how to avoid the adverse event is important. It is challenging because when adverse events are rare, determining causation or even rate is often difficult to the point of impossibility.

An example might be the use of isotretinoin for acne and reports of suicide, especially in young men. A search found three recent papers, two of them systematic reviews, which help to some extent, but will be deeply unsatisfying to anyone who wants to find a connection between treatment and suicide.

Systematic reviews


Both systematic reviews [1,2] searched three of four large and relevant databases, essentially for any study including the drug, and depression or suicide, and in humans. The formal studies could be cohort studies or randomised trials. One included case reports [1], while the other [2] did not.

Results


Surprisingly, given the general similarity in inclusion criteria, only four studies were common to both reviews.

The first review included case reports as well as formal studies, mainly from reports to registration authorities. Case reports included depression, psychiatric reactions, and some suicide ideation, suicide attempts, and completed suicides. In 25 cases documented by the FDA, cessation of drug was associated with resolution of mood disturbance, and reinstitution followed by a period of depression.

Many of the studies were small, and only two examined suicidal behaviour and isotretinoin use. One found no events, and the other, looking at attempted and completed suicide together, found 37 such events in 35,000 person-years of isotretinoin exposure. The only predictor was a previous history of depression or psychosis, which had an 8-fold increased risk.

New cohort study [3]


In 2003 all cases of psychosis associated with exposure to isotretinoin among conscripts in the Israeli Defence Force were reviewed. In this period 500 conscripts were seen for severe acne by a dermatologist. There were five cases, three female, aged 19 or 20 years, all treated with isotretinoin before developing psychiatric morbidity. All had undergone pre-intake assessment at age 17, including a review of psychiatric history. The lag time was between three and 11 months, with a median of eight months. Three of the five soldiers had attempted suicide.

In all five cases there were predisposing factors, including obsessive-compulsive disorder, family history of schizophrenia or bipolar disorder, pituitary tumour, or intractable headache after head trauma. Three had more than one predisposing condition. One of the cases has a sibling with a manic episode after isotretinoin treatment.

Comment


It is impossible to say from the evidence available that there is a link between isotretinoin and suicidal behaviour. Neither is it impossible to say that there is no such link. But there are now two tenuous pieces of evidence to suggest that giving isotretinoin to young people with acne who either themselves have depression or psychiatric history, or who have a family history, may not be the best of ideas.

Young people have higher suicide risk, and acne has itself been associated with increased depression and suicidal behaviour. So is mental illness, and the lifetime risk of suicide is 1 in 20 in schizophrenia [4]. Very high suicide risks can occur on admission to and after discharge from psychiatric hospitals [5].

For a young person with acne and a personal or family history of depression or mental illness, the risk of suicide or suicidal behaviour must be high. Whether treating acne with isotretinoin increases the risk further is an almost impossible question to answer. It may be best avoided in those circumstances by appropriate history-taking.

The issue here, like so many other cases, is not so much whether therapies are effective or harmful, but in whom they are effective or harmful. This is a much under-researched area, where regulation and trials fail practice. It also asks some fundamental questions about our priorities.

References:



  1. P Magin et al. Isotretinoin, depression and suicide: a review of the evidence. British Journal of General Practice 2005 55: 134-138.
  2. AL Marqueling, LT Zane. Depression and suicidal behaviour in acne patients treated with isotretinoin: a systematic review. Seminars in Cutaneous Medicine and Surgery 2005 24: 92-102.
  3. Y Barak et al. Active psychosis following Accutane (Isotretinoin) treatment. International Clinical Psychopharmacology 2005 20: 39-41.
  4. BA Palmer et al. The lifetime risk of suicide in schizophrenia. Archives of General Psychiatry 2005 62: 247-252.
  5. P Qin, M Nordentoft. Suicide risk in relation to psychiatric hospitalization. Archives of General Psychiatry 2005 62: 427-432.

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