A large, retrospective cohort study is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.
By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease - severe acne - than with the isotretinoin, and may be affected by treatment failure.
Pharmacoepidemiologist Anders Sundstrom of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15-49 years) who were prescribed isotretinoin in 1980-1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5 mg and 39.2 mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients' clinical records were compared with hospital-discharge and cause-of-death registers for the 1980-2001 period.
In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54-1.37) at 3 years before treatment to 1.36 (95% CI, 0.65-2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65-1.44) at 3 years before treatment to 1.57 (95% CI, 0.86-2.63) in the year before treatment for all attempts.
The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08-3.18) for first attempts and 1.78 (95% CI, 1.04-2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.
After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64-1.40) for first attempts and 1.04 (95% CI, 0.74-1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.
The investigators concluded that "an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin." However, they wrote, "the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established." Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but "close monitoring of patients for suicidal behavior for up to a year after treatment has ended" would be advisable (BMJ 2010 Nov. …