Antidepressant
PREGNANCY RECOMMENDATION: Human Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
Although the data are limited, desipramine does not appear to be a major human teratogen.
FETAL RISK SUMMARY
Desipramine, a tricyclic antidepressant, is an active metabolite of imipramine (see also Imipramine). No reports linking the use of desipramine with congenital defects have been located. Neonatal withdrawal symptoms, including cyanosis, tachycardia, diaphoresis, and weight loss, were observed after desipramine was taken throughout pregnancy (1).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 31 newborns had been exposed to desipramine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (3.2%) major birth defect was observed (one expected). No anomalies were observed in six defect categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. The number of exposures is too small for comment.
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 (2). Multiple drug therapy occurred in about two-thirds of the mothers. Desipramine was used in one pregnancy and the outcome was a spontaneous abortion.
In an in vitro study, desipramine was shown to be a potent inhibitor of sperm motility (3). A concentration of 27 µmol/L produced a 50% reduction in motility.
A 2002 prospective study compared two groups of mother-child pairs: one group exposed to antidepressants throughout gestation (46 exposed to tricyclics - 3 to desipramine; 40 to fluoxetine) and, the other group, 36 nonexposed, not depressed controls (4). Offspring between the ages 15 and 71 months were studied for effects of antidepressant exposure in terms of IQ, language, behavior, and temperament. Exposure to antidepressants did not adversely affect the measured parameters, but IQ was significantly and negatively associated with the duration of depression, and language was negatively associated with the number of depression episodes after delivery (4).
BREASTFEEDING SUMMARY
Desipramine is excreted into breast milk (5–7). No reports of adverse effects have been located. In one patient, milk:plasma ratios of 0.4–0.9 were measured with milk levels ranging between 17 and 35 mcg/mL (5). A 35-year-old mother in her 9th postpartum week took 300 mg of desipramine daily at bedtime for depression (7). One week later, simultaneous milk and serum samples were collected about 9 hours after a dose. Concentrations of desipramine in the milk and serum were 316 and 257 ng/mL (ratio 1.2), respectively, whereas levels of the metabolite, 2-hydroxydesipramine, were 381 and 234 ng/mL (ratio 1.6), respectively. The measurements were repeated 1 week later, 10.33 hours after the dose, and milk levels of the parent drug and metabolite were 328 and 327 ng/mL, respectively. No drug was detected in the infant’s serum nor were any clinical signs of toxicity observed in the infant after 3 weeks of maternal treatment (7).
A 1996 review of antidepressant treatment during breastfeeding found no information that desipramine exposure during nursing resulted in quantifiable amounts in an infant or that the exposure caused adverse effects (8). The American Academy of Pediatrics classifies desipramine as a drug whose effect on the nursing infant is unknown but may be of concern (9).
References
1.Webster PA. Withdrawal symptoms in neonates associated with maternal antidepressant therapy. Lancet 1973;2:318–9.
2.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.
3.Levin RM, Amsterdam JD, Winokur A, Wein AJ. Effects of psychotropic drugs on human sperm motility. Fertil Steril 1981;36:503–6.
4.Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002;159:1889–95.
5.Sovner R, Orsulak PJ. Excretion of imipramine and desipramine in human breast milk. Am J Psychiatry 1979;136:451–2.
6.Erickson SH, Smith GH, Heidrich F. Tricyclics and breast-feeding. Am J Psychiatry 1979;136:1483.
7.Stancer HC, Reed KL. Desipramine and 2-hydroxydesipramine in human breast milk and the nursing infant’s serum. Am J Psychiatry 1986;143:1597–600.
8.Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996;153:1132–7.
9.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.