Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies

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Abstract
Background A substantial number of women of childbearing age suffer from depression. Despite this, relatively little is known about the safety of antidepressant use during pregnancy. Purpose We conducted a meta‐analysis of prospective comparative cohort studies to quantify the relationship between maternal exposure to the newer antidepressants and major malformations. Methods We searched Medline, Embase and Reprotox from 1996 to the present for studies comparing outcomes in first trimester exposures to citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, reboxetine, venlafaxine, nefazodone, trazodone, mirtazapine and bupropion to those of non‐exposed mothers. Data were combined using a random effects model; heterogeneity was tested with χ2, and publication bias with a funnel plot and the Begg–Mazumdar statistic. Results Twenty‐two studies were identified, 15 were rejected (4 reviews, 4 without comparison groups, 2 third trimester exposures, 2 retrospective database studies, 2 case reports and 1 duplicate); 7 studies (n = 1774) met inclusion criteria. Effects were not heterogeneous (χ2 = 2.04, p = 0.92); funnel plot and test (τ = −0.24, p = 0.45) indicated no publication bias. The summary relative risk was 1.01 (95%CI: 0.57–1.80). Conclusions As a group, the newer antidepressants are not associated with an increased risk of major malformations above the baseline of 1–3% in the population. Copyright © 2005 John Wiley & Sons, Ltd.