Possible teratogenic effects of imipramine in the rat.

Abstract

Tricyclic antidepressants are sometimes used during pregnancy (Crombie et al. 1972; Scanlon 1969). In reviews of studies which examine the teratogenic potential of antidepressants in humans it is frequently concluded that these drugs are relatively safe for use in pregnant patients (Calabrese and Gulledge 1985; Csernansky and Hollister 1984). While ethical and experimental restraints prohibit a thorough assessment of the results of prenatal drug exposure in humans, animal experiments have indicated that physiologic, biochemical, and behavioral effects may result from in utero drug exposure. Collectively, our pharmacokinetic and dynamic studies indicate that third trimester administration of imipramine (IMI) to rats in doses that do not cause dysmorphic effects in the fetus results in substantial fetal drug and metabolite exposure, enhances infant mortality, and has teratogenic effects persisting into adulthood on neuronal systems which regulate growth and reproductive function. These data imply that maternal ingestion of imipramine may result in subclinical teratogenic effects, which may not be evident, if at all, until offspring have matured past adolescence.