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


OBJECTIVE
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 chi2, 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 (chi2 = 2.04, p = 0.92); funnel plot and test (tau = -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.
Einarson
Thomas R
TR
Faculty of Pharmacy, Department of Clinical Pharmacology, Faculty of Medicine, University of Toronto, Ont., Canada.
Einarson
Adrienne
A
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015201:Meta-Analysis as Topic; D011247:Pregnancy / Q000706:statistics & numerical data*; D011261:Pregnancy Trimester, First; D012306:Risk; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D017367:Selective Serotonin Reuptake Inhibitors