Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris: A Case-Crossover Study

Laurent Azoulay, M.Sc.; Lucie Blais, Ph.D.; Gideon Koren, M.D.; Jacques LeLorier, M.D., Ph.D.; and Anick Bérard, Ph.D.

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 >= 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-Écho) 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 >= 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.

(J Clin Psychiatry 2008;69:526-532. Online Ahead of Print March 5, 2008.)

Received June 26, 2007; accepted Aug. 27, 2007. From the Departments of Pharmacy (Drs. Blais and Bérard and Mr. Azoulay) and Medicine (Dr. LeLorier) and CHU Sainte-Justine Research Center (Dr. Bérard and Mr. Azoulay), University of Montreal; the Research Center, Sacré-Coeur Hospital (Dr. Blais), Montreal, Quebec; Motherisk Program, Hospital for Sick Children, University of Toronto, Ontario, and Ivey Chair in Molecular Toxicology, University of Western Ontario, London (Dr. Koren), Canada.

This study was supported by Canadian Institutes of Health Research (CIHR) grant IHD-67337. Mr. Azoulay was the recipient of a doctoral bursary from the Fonds de la recherche en santé du Québec. Dr. Bérard is the recipient of a career award from the CIHR/Canadian Foundation for Health and is on the endowment research chair of the Famille Louis-Boivin on "Medications, Pregnancy and Lactation" at the Department of Pharmacy, University of Montreal, Quebec, Canada.

This study was presented at the 22nd International Conference on Pharmacoepidemiology & Therapeutic Risk Management; Aug. 24-27, 2006; Lisbon, Portugal.

The authors report no additional financial or other affiliation related to the subject of this article.

Corresponding author and reprints: Anick Bérard, Ph.D., CHU Sainte-Justine Research Centre, 3175, chemin de la Côte-Ste-Catherine, Montreal (Quebec), Canada H3T 1C5 (e-mail: anick.berard@umontreal.ca).