New Study: Authors Implicate Acne, Rather Than Accutane, for Increasing Suicide Risk

There are mixed messages from a newly published Swedish study, which examined the potential association between suicidal behavior and Accutane, but the authors correctly hedge their overall finding with some important caveats. 

The blunt-force trauma of the study is that there is a significantly increased risk of suicide attempts during the first 6 months of Accutane treatment.* According to data from Sweden's socialized-medicine database, the standardized incidence ratio** for all suicide attempts (n = 128 among 5756 treated patients) was 1.78 (95% CI: 1.04, 2.85) and that for first-time attempts was 1.93 (95% CI: 1.08, 3.18). Moreover, these incidence ratios declined after the completion of Accutane therapy (see Table). The knee-jerk conclusion: Accutane increases the risk of attempted suicide.

Time period	Incidence Ratio (95% CI)
	First Suicide Attempts	All Suicide Attempts
3 years before treatment	0.89 (0.54, 1.37)	0.99 (0.65, 1.44)
1 year before treatment	1.36 (0.65, 2.50)	1.57 (0.86, 2.63)
6 months after treatment start	1.93 (1.08, 3.18)	1.78 (1.04, 2.85)
3 years after treatment	0.97 (0.64, 1.4)	1.04 (0.74, 1.43)

However, however:

The authors stressed that the incidence ratios for attempted suicide were already increasing before Accutane therapy—for unclear reasons, but possibly as a result of despondence over progressive acne. The authors speculated,  

Considering the increasing risk of attempted suicide during the years before treatment, we cannot state whether the continued rise during and immediately after treatment was due to the natural course of severe acne or to negative effects of the treatment.

Alternative explanations for the relative increase in suicide attempts during Accutane treatment were also provided:

• Despair over a lack of acne improvement
• Despair over a lack of improvement in social life after clearing of acne

The possibility that suicidal behavior may be related to acne rather than Accutane treatment could also explain the declining ratios after the completion of therapy, when acne had cleared because of Accutane treatment. The authors concluded,

We must stress that we cannot exclude the possibility that the raised risk of suicide attempts during treatment and six months after treatment is due to the exposure to isotretinoin. However, a more probable interpretation is that the underlying severe acne may best explain the raised risk.

Supporting this conclusion is the observation that patients (n = 32) who made their first suicide attempt before treatment did not seem to have their suicidal behavior reinforced during or after Accutane treatment: Only 38% of these patients made new suicide attempts or committed suicide during follow-up. On the other hand, among the 14 patients who made a first suicide attempt during treatment or within 6 months after the end of treatment, 71% made a new attempt or committed suicide during follow-up.

* The mean length of Accutane treatment was approximately 6 months.

** The denominator was the age-, sex-, and season-adjusted background rate of suicide attempts for the population.

N.B. A previous review of the literature at this blog suggests that the risk of suicide with Accutane treatment is idiosyncratic.