Exposure to Mirtazapine During Pregnancy: A Prospective, Comparative Study of Birth Outcomes

Background: Mirtazapine is a novelpiperazinoazepine antidepressant, unrelated to any known class ofantidepressants. Currently, apart from a few case reports andcase series in the literature, there are no studies evaluatingthe safety of this drug during pregnancy.

Objective: To determine whether mirtazapineincreases the risk for major malformations in newborns when usedby pregnant women.

Method: The study design was prospective, with 2comparison groups: disease-matched pregnant women diagnosed withdepression taking other antidepressants and pregnant womenexposed to nonteratogens. The primary outcome was majormalformations in neonates; secondary endpoints includedspontaneous abortions, therapeutic abortions, gestational age atbirth, and mean birth weight. Women were recruited from 5teratogen 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, UnitedKingdom. Women were recruited into the study from June 2002 toAugust 2005.

Results: We were able to follow 104 pregnancyoutcomes in each drug group. There were 77 live births, 1stillbirth, 20 spontaneous abortions, 6 therapeutic abortions,and 2 major malformations in the mirtazapine group. The mean ± SDbirth weight was 3335 ± 654g and the mean ± SD gestational age atdelivery was 38.9 ± 2.5 weeks. Most (95%) of the women took mirtazapine in the first trimester, but only 25% of the womentook it throughout pregnancy. The differences among the 3 groupswere in the rate of spontaneous abortions, which was higher inboth 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 statisticallysignificant. The rate of preterm births (prior to 37 weeks’gestation) was also higher in the mirtazapine group (10%) and inthe other antidepressant group (7%) than in the nonteratogengroup (2%). The difference was statistically significant betweenthe mirtazapine group and the nonteratogen group (p = .04).

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