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PSYCHIATRY

Antidepressant Use During Pregnancy and the Rates of Spontaneous Abortions: A Meta-Analysis

at time of writing, MSc Student, Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Motherisk Program, Hospital For Sick Children, Toronto

Adrienne Einarson, RN

Assistant Director, Motherisk Program, Hospital For Sick Children

Gideon Koren, MD

Professor, Department of Pharmacology, Faculty of Medicine, University of Toronto, Hospital For Sick Children

Krista L Lanctôt, PhD

Assistant Professor, Department of Pharmacology, University of Toronto

Thomas R Einarson, PhD

Associate Professor, Leslie Dan Faculty of Pharmacy, University of Toronto

Reprints: Dr. Einarson, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, ON M5S 2S2, Canada, fax 416/978-1833, t.einarson{at}utoronto.ca

BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy.

OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates.

METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy.

RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (² 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes.

CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.

Key Words: antidepressants, depression, spontaneous abortion

Published Online, March 22, 2005. www.theannals.com, DOI 10.1345/aph.1E547

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