Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes.
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.


METHODS
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 +/- 654 g 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).


CONCLUSIONS
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.
Djulus
Josephine
J
Motherisk Program, Division of Clinical Pharmacology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Koren
Gideon
G
Einarson
Thomas R
TR
Wilton
Lynda
L
Shakir
Saad
S
Diav-Citrin
Orna
O
Kennedy
Deborah
D
Voyer Lavigne
Sharon
S
De Santis
Marco
M
Einarson
Adrienne
A
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000209:etiology; D000022:Abortion, Spontaneous / Q000139:chemically induced / Q000453:epidemiology; D000032:Abortion, Therapeutic / Q000706:statistics & numerical data; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000627:therapeutic use; D001724:Birth Weight; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D018811:Maternal Exposure; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011261:Pregnancy Trimester, First; D047928:Premature Birth / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies; D018570:Risk Assessment; D006113:United Kingdom / Q000453:epidemiology
D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine