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News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD

Severe acne is associated with the risk for suicide attempt even before treatment with isotretinoin was started, although the risk is increased during treatment and up to 6 months afterward, according to the results of a retrospective Swedish cohort study reported online first November 12 in the BMJ.

“Isotretinoin (13-cis-retinoic acid) has been used since the 1980s to treat severe recalcitrant nodular acne with good effect, but case reports and spontaneous reporting of adverse drug reactions have suggested an association between isotretinoin, depression, and suicidal behaviour,” write Anders Sundström, from the Karolinska Institute in Stockholm, Sweden, and colleagues. “Observational studies have had conflicting results, however.”

The goal of the study was to evaluate the risk for attempted suicide before, during, and after treatment with isotretinoin for severe acne. In Sweden from 1980 to 2001, a named patient register of isotretinoin users from 1980 to 1989 was linked to hospital discharge and cause-of-death registers from 1980 to 2001. The investigators identified 5756 patients aged 15 to 49 years who were prescribed isotretinoin for severe acne and who were observed for a total of 17,197 person-years before treatment, 2905 person-years during treatment, and 87,120 person-years after treatment.

The standardized incidence ratio (SIR), defined as the observed number of suicide attempts divided by the expected number and standardized by sex, age, and calendar year, was calculated up to 3 years before, during, and up to 15 years after treatment was completed.

During the study period, 128 patients were admitted to the hospital for attempted suicide. The SIR for attempted suicide was increased during the year before treatment: 1.57 (95% confidence interval [CI], 0.86 – 2.63) for all, including repeated attempts, and 1.36 (95% CI, 0.65 – 2.50) for only first attempts.

The risk for suicide attempts was further increased during and up to 6 months after treatment, with a SIR of 1.78 (95% CI, 1.04 – 2.85) for all attempts and 1.93 (95% CI, 1.08 – 3.18) for first attempts. At 3 years after treatment was stopped, the observed number of suicide attempts was close to the expected number, and this remained stable during 15-year follow-up, with a SIR of 1.04 (95% CI, 0.74 – 1.43) for all attempts and 0.97 (95% CI, 0.64 – 1.40) for first attempts.

Of 32 patients who made their first suicide attempt before treatment, 12 (38%) made a new attempt or committed suicide thereafter, whereas 10 (71%) of the 14 patients who made their first suicide attempt within 6 months after treatment was stopped made a new attempt or committed suicide during follow-up (2-sample test of proportions, P = .034).

For 1 additional first suicide attempt to occur, the number needed to harm was 2300 new 6-month treatments per year. For 1 additional repeated attempt, the number needed to harm was 5000 per year.

“An increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin, which motivates a close monitoring of patients for suicidal behaviour for up to a year after treatment has ended,” the study authors write. “However, the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established. As patients with a history of suicide attempts before treatment made new attempts to a lesser extent than did patients who started such behaviour in connection with treatment, patients with severe acne should not automatically have isotretinoin treatment withheld because of a history of attempted suicide.”

Limitations of this study include low statistical precision, estimation of exposure to isotretinoin from prescriptions vs actual use, lack of data on the effect of treatment, minor loss to follow-up, and inability to account or control for effects of risk factors changing within a person with time.

In an accompanying editorial, Parker Magin and John Sullivan, both from Australia, concur that it is essential for patients treated with isotretinoin for acne to be carefully monitored for depression and suicidal thoughts, especially among patients for whom treatment is unsuccessful.

“It is difficult to tease out the relation between mental health and isotretinoin because acne itself is associated with psychiatric morbidity, including depression,” Drs. Magin and Sullivan write.

The Swedish Research Council supported this study. The study authors and editorialists have disclosed no relevant financial relationships.

BMJ. 2010;341:c5812, c5866.

The National Association of School Psychologists provides a number of resources for healthcare professionals, educators, parents, and teenagers on preventing youth suicide.

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