A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy.

Objectives: Trazodone and nefazodone are phenylpiperazine antidepressants. Currently, there are no adequate, well-controlled studies on the fetal safety of these drugs. Our primary objective was to determine whether the use of trazodone or nefazodone during pregnancy is associated with an increased risk for major malformations. Secondary outcomes of interest included rates of spontaneous and therapeutic abortions, rates of premature labour, and birth weight.

Methods: Pregnant women from 5 centres who had been exposed to these drugs (n = 147) were enrolled in the study during their first trimester. We compared the women with 2 groups of women who took either other antidepressant drugs (n = 147) or nonteratogenic drugs (n = 147). All the women were followed up after delivery to ascertain pregnancy outcome and the health of the baby.

Results: We have completed 147 follow-ups. There were 121 (82.4%) live births, 20 (13.6%) spontaneous abortions, and 6 (4%) therapeutic abortions. Of the live births, there were 2 (1.6%) major malformations. In all cases, drug exposure occurred during the first trimester, with 52 (35%) of the women using these drugs throughout pregnancy. The mean gestational age at birth was 38 weeks (SD 4.2), and the mean birth weight was 3306.34 g (SD 655). We found no statistically significant differences among the 3 groups in any of the endpoints of interest that we examined. Of the sample, 58 women were exposed to trazodone, and 89 were exposed to nefazodone.

Conclusion: Our results suggest that these drugs do not increase the rates of major malformations above the baseline rate of 1% to 3%.