Does isotretinoin increase the risk of depression?

Question: In patients with acne vulgaris, does treatment with isotretinoin increase the risk of depression? Design: A case-crossover study was performed among subjects who received 1 or more isotretinoin prescriptions from 1984 through 2003. Setting: Data were obtained from the Régie de l’Assurance Maladie du Québec (RAMQ) and Quebec’s hospital discharge (Med-Echo) administrative databases. Patients: Cases were defined as those with a first diagnosis or hospitalization for depression (International Classification of Diseases, Ninth Revision codes 296.2, 298.0, 300.4, 309.0, 309.1, and 311) during the study period (1984-2003) and those who filled a prescription for an antidepressant in the 30 days following their diagnosis or hospitalization. The index date was the calendar date of the diagnosis or hospitalization for depression. Cases were covered by the RAMQ drug plan and had 1 or more acne diagnoses in the 12 months prior to the index date. Those who received an antidepressant in the 12 months prior to the index date were excluded. Intervention: Exposure to isotretinoin in a 5-month risk period immediately prior to the index date was compared with a 5-month control period. Outcome: Relative risks along with 95% confidence intervals were estimated using conditional logistic regression. Results: Of the 30 496 subjects in the initial cohort, 126 (0.4%) cases met inclusion criteria. The crude relative risk for those exposed to isotretinoin was 2.00 (95% confidence interval, 1.03 to 3.89). After adjusting for potential time-dependent confounders, the relative risk for those exposed to isotretinoin was 2.68 (95% confidence interval, 1.10 to 6.48). Conclusions: This is the first controlled study to find a statistically significant association between isotretinoin and depression. Because depression could have serious consequences, close monitoring of isotretinoin users is indicated. Comment