Antidepressant
PREGNANCY RECOMMENDATION: Human Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
The animal data suggest low risk but, if the comparison to the human dose had been based on BSA, the toxic dose would have been close to the human dose. The human data are too limited to assess the risk to the embryo–fetus. In general, though, most tricyclic antidepressants do not have a known teratogenic effect in humans (1). In addition, of the tricyclic antidepressants, nortriptyline and desipramine are preferred during pregnancy because they have the least sedative action and maternal adverse effects (1).
FETAL RISK SUMMARY
Trimipramine is a tricyclic antidepressant in the same class as amitriptyline, clomipramine, doxepin, and imipramine. It is indicated for the relief of symptoms of depression (2). Trimipramine has an elimination half-life of 9–11 hours and it is metabolized in the liver to an active metabolite (3).
Reproduction studies have been conducted in rats, rabbits, and mice. In rats and rabbits, evidence of embryotoxicity and/or increased incidence of major anomalies (type not specified) were observed at doses 20 times the human dose (2). A single SC dose given to mice on day 9 of gestation resulted in exencephaly and other defects of the central nervous system (4). In the isolated rat uterus, trimipramine had greater antihistamine H2 activity than cimetidine, amitriptyline, or imipramine (5).
It is not known if trimipramine or its active metabolite crosses the human placenta. The molecular weight of the free base (about 294) and the long elimination half-life suggest that both compounds will cross to the embryo–fetus.
In a 1996 descriptive case series, the European Network of the Teratology Information Services (ENTIS) prospectively examined the outcomes of 689 pregnancies exposed to antidepressants (6). Multiple drug therapy occurred in about two-thirds of the mothers. There were nine exposures to trimipramine. The outcomes of these pregnancies were eight normal newborns (including three premature infants) and one normal infant with a neonatal disorder (bilateral metatarsus varus [possibly positional]) (6).
BREASTFEEDING SUMMARY
No reports describing the use of trimipramine during human lactation have been located. The molecular weight of the free base (about 294) and the long elimination half-life (9–11 hours) suggest that both compounds will be excreted into milk. The effect of this exposure on a nursing infant is unknown. However, the American Academy of Pediatrics classifies other tricyclic antidepressants as drugs whose effect on the nursing infant is unknown but may be of concern (see Amitriptyline).
References
1.Committee on Drugs, American Academy of Pediatrics. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics 2000;105:880–7.
2.Product information. Surmontil. Odyssey Pharmaceuticals, 2004.
3.Parfitt K, ed. Martindale: The Complete Drug Reference. 32nd ed. London, UK: Pharmaceutical Press, 1999:310.
4.Jurand A. Malformations of the central nervous system induced by neurotropic drugs in mouse embryos. Develop Growth Differ 1980;22:61–78. As cited by Shepard TH. Catalog of Teratogenic Agents. 10th ed. Baltimore, MD: The Johns Hopkins University Press, 2001:510.
5.Alvarez FJ, Casas E, Franganillo A, Velasco A. Effects of antidepressants on histamine H2 receptors in rat isolated uterus. J Pharmacol (Paris) 1986;17:351–4.
6.McElhatton PR, Garbis HM, Elefant E, Vial T, Bellemin B, Mastroiacovo P, Arnon J, Rodriguez-Pinilla E, Schaefer C, Pexieder T, Merlob P, Dal Verme S. The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS). Reprod Toxicol 1996;10:285–94.