Exposure to Mirtazapine During Pregnancy: A Prospective, Comparative Study of Birth Outcomes
Josephine Djulus, MD; Gideon Koren, MD; Thomas R. Einarson, PhD; Lynda Wilton, PhD; Saad Shakir, MD; Orna Diav-Citrin, MD; Deborah Kennedy, MD; Sharon Voyer Lavigne, MSc; Marco De Santis, MD; and Adrienne Einarson, RN
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
© Copyright 2006 Physicians Postgraduate Press, Inc.