November 12, 2010 — A large retrospective study appears to confirm a recent previous study that suicidal behavior in individuals with severe acne is linked to the disease, and not to treatment with isotretinoin.

The study also shows that an additional risk may be present during and up to 1 year after treatment with isotretinoin. However, investigators stress that this additional risk is most likely a result of the acne itself, rather than treatment with the drug.

"Severe acne is not a trivial condition; in the absence of treatment with isotretinoin, it is associated with an increased risk of attempted suicide," write investigators led by Anders Sundstrom, a pharmacoepidemiologist from the Karolinska Institute, Sweden.

The study was published online November 12 in BMJ.

Isotretinoin has been used to treat acne since the 1980s, with effective results. Although the study authors note that there has been research linking the drug to depression and suicidal behavior, the findings have been conflicting.

"The association between acne, psychiatric morbidity, and suicide attempts has been described, and some authors have observed that isotretinoin actually lead to an improvement in anxiety and depression because of the clearing of disfiguring acne," they write.

The investigators hypothesized that those with acne are at higher risk for suicide regardless of whether they are taking isotretinoin. They analyzed data from 5756 individuals aged 15 to 49 years who were prescribed isotretinoin for severe acne between 1980 and 1989. These data were then linked to data from hospital discharge and cause-of-death registers from 1980 to 2001.

Of the total cohort, 3613 were men. The average age of the patients when they were first prescribed isotretinoin was 22 years for men and 27 years for women.

The main outcome measure was the standardized incidence ratio, which was the observed number of suicides divided by the expected number of suicide attempts calculated up to 3 years before, during, and up to 15 years after the end of treatment.

A total of 128 patients were admitted to the hospital for attempted suicide. During the year before treatment, the standardized incidence ratio for attempted suicide was raised by 1.57 (95% confidence interval [CI], 0.86 - 2.63) for all suicide attempts, including repeat attempts, and 1.36 for first attempts only (95% CI, 0.65 - 2.50).

The standardized incidence ratio during and up to 6 months after treatment was 1.78 (95% CI, 1.04 - 2.85) for all attempts and 1.93 (95% CI, 1.08 - 3.18) for first attempts.

The investigators report that 3 years after treatment stopped, the observed number of attempts was close to the expected number and remained so during 15 years of follow-up, with a standardized incidence ratio of 1.04 (95% CI, 0.74 - 1.43) for all attempts and 0.97 (95% CI, 0.64 - 1.40) for first attempts.

The study authors speculate that the finding that the risk for attempted suicide was highest within 6 months after treatment ended may be because patients whose acne and physical appearance improved after treatment were distraught if there was no improvement in their social life.

"We must stress that we cannot exclude the possibility that the raised risk of suicide attempts during treatment and 6 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," the study authors write.

These findings appear to support results of a recent study published September 16 in the Journal of Investigative Dermatology and reported by Medscape Medical News at that time, which suggested that suicidal ideation in this population may reflect the burden of the disease, rather than treatment with isotretinoin.

"Physicians prescribing isotretinoin should be aware that a history of psychiatric problems, such as suicide, need not constitute a decisive factor when considering treatment with isotretinoin.

"Much more important is the fact that suicide attempts can occur quite a long time after treatment has stopped. For this reason, close monitoring of the mental status of patients receiving isotretinoin, as well as those with severe acne, should be a part of the treatment process and should continue for at least a year after the end of treatment."

In an accompanying editorial, Parker Magin, MD, PhD, from the University of Newcastle, in Callaghan, Australia, and John Sullivan, MD, from the University of New South Wales, in Sydney, Australia, acknowledge that "it is difficult to tease out the relationship between mental health and isotretinoin because acne itself is associated with psychiatric morbidity, including depression.

"Clinicians can draw important practical conclusions from this study, which are relevant whether isotretinoin is or is not, directly or indirectly, causally implicated in suicide. During and after treatment with isotretinoin (perhaps, especially, unsuccessful treatment), patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored," they write.

The study authors have disclosed no relevant financial relationships.

BMJ. Published online November 11, 2010.