Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study

J Clin Psychiatry. 2008 Apr;69(4):526-32. doi: 10.4088/jcp.v69n0403.


Objective: To determine whether isotretinoin increases the risk of depression in patients with acne vulgaris.

Method: A case-crossover study was performed among subjects who received > or = 1 isotretinoin prescription from 1984 through 2003. Data were obtained from the Régie de l'Assurance Maladie du Québec (RAMQ) and Quebec's hospital discharge (Med-Echo) administrative databases. Cases were defined as those with a first diagnosis or hospitalization for depression (ICD-9 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 > or = 1 acne diagnosis in the 12 months prior to the index date. Those who received an antidepressant in 12 months prior to the index date were excluded. Exposure to isotretinoin in a 5-month risk period immediately prior to the index date was compared to a 5-month control period. Relative risks along with 95% CIs 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% CI = 1.03 to 3.89). After adjusting for potential time-dependent confounders, the relative risk for those exposed to isotretinoin was 2.68 (95% CI = 1.10 to 6.48).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Acne Vulgaris / epidemiology
  • Adult
  • Case-Control Studies
  • Cross-Over Studies
  • Depression / chemically induced*
  • Depression / epidemiology*
  • Depression / rehabilitation
  • Dermatologic Agents / adverse effects*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Administration Schedule
  • Emergency Services, Psychiatric / statistics & numerical data
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Isotretinoin / adverse effects*
  • Male
  • Office Visits / statistics & numerical data
  • Prevalence
  • Risk Factors
  • Severity of Illness Index
  • Suicide / statistics & numerical data


  • Dermatologic Agents
  • Isotretinoin