Background: Mirtazapine is a novel piperazinoazepine antidepressant, unrelated to any known class of antidepressants. Currently, apart from a few case reports and case series in the literature, there are no studies evaluating the safety of this drug during pregnancy.

Objective: To determine whether mirtazapine increases the risk for major malformations in newborns when used by pregnant women.

Method: The study design was prospective, with 2 comparison groups: disease-matched pregnant women diagnosed with depression taking other antidepressants and pregnant women exposed to nonteratogens. The primary outcome was major malformations in neonates; secondary endpoints included spontaneous abortions, therapeutic abortions, gestational age at birth, and mean birth weight. Women were recruited from 5 teratogen information services in Toronto, Canada; Farmington, Conn., U.S.A.; Jerusalem, Israel; Rome, Italy; Sydney, Australia; and from the Drug Safety Research Unit in Southampton, United Kingdom. Women were recruited into the study from June 2002 to August 2005.

Results: We were able to follow 104 pregnancy outcomes in each drug group. There were 77 live births, 1 stillbirth, 20 spontaneous abortions, 6 therapeutic abortions, and 2 major malformations in the mirtazapine group. The mean ± SD birth weight was 3335 ± 654g and the mean ± SD gestational age at delivery was 38.9 ± 2.5 weeks. Most (95%) of the women took mirtazapine in the first trimester, but only 25% of the women took it throughout pregnancy. The differences among the 3 groups were in the rate of spontaneous abortions, which was higher in both antidepressant groups (19% in the mirtazapine group and 17% in the other antidepressant group) than in the nonteratogen group (11%), but none of the differences were statistically significant. The rate of preterm births (prior to 37 weeks' gestation) was also higher in the mirtazapine group (10%) and in the other antidepressant group (7%) than in the nonteratogen group (2%). The difference was statistically significant between the mirtazapine group and the nonteratogen group (p = .04).

Conclusion: Mirtazapine does not appear to increase the baseline rate of major malformations of 1% to 3%. However, the higher number of spontaneous abortions in the antidepressant groups confirms the higher rates of spontaneous abortions in pregnant women taking antidepressant medications found in previous studies.

J Clin Psychiatry 2006;67(8):1280-1284