TRAZODONE

Fetal Risk Summary

No published reports of the use of trazodone in human pregnancy have been located. At high doses in some animal species, trazodone is fetally toxic and teratogenic.

One manufacturer has received several anecdotal descriptions concerning the use of trazodone in pregnancy (T. Donosky, personal communication, Mead Johnson Pharmaceutical Division, 1987). Included in these was a report of an infant born with an undefined birth defect after in utero exposure to the antidepressant. Another report described a normal infant exposed throughout gestation beginning with the 5th week. No confirmatory follow-up information was available for either of these cases. A third case from the manufacturer's files involved a woman who took trazodone, 50–100 mg/day, during the first 3 weeks of pregnancy and eventually delivered a normal infant. Finally, a woman was treated with trazodone for 8 days, at which time the drug was discontinued because of a positive pregnancy test. A spontaneous abortion occurred approximately 1.5 months later. No cause-and-effect relationship can be inferred between trazodone and any of the above adverse outcomes.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 100 newborns had been exposed to trazodone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (1%) major birth defect was observed (four expected), but details are not available. 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.

A prospective multicenter study evaluated the effects of lithium exposure during the 1st trimester in 148 women (1). One of the pregnancies was terminated at 16 weeks' gestation because of a fetus with the rare congenital heart defect, Ebstein's anomaly. The fetus had been exposed to lithium, trazodone, fluoxetine, and L-thyroxine during the 1st trimester. The defect was attributed to lithium exposure.

Breast Feeding Summary

Trazodone is excreted into human milk (2). In six healthy lactating women, 3–8 months postpartum, a single 50-mg oral dose of trazodone was given after an overnight fast. Simultaneous serum and milk samples were collected at various times up to 30 hours after ingestion. The infants of the mothers were not allowed to breast-feed during the first 4 hours after the dose. The mean milk:plasma ratio, based on the concentration-time curves for the two fluids, was 0.142. Based on 500 mL of milk consumed during a 12-hour interval, the infants would have received a trazodone dose of 0.005 mg/kg (2). This study was unable to include a potentially active metabolite, 1-m-chlorophenylpiperazine, in the analysis (2). Although the amount of trazodone in milk is very small, the American Academy of Pediatrics considers the potential effects of trazodone on the nursing infant to be unknown, but of possible concern (3).

References

1. Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, Donnenfeld AE, Rieder M, Santelli R, Smythe J, Pastuszak A, Einarson T, Koren G. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992;339:530–3.
2. Verbeeck RK, Ross SG, McKenna EA. Excretion of trazodone in breast milk. Br J Clin Pharmacol 1986;22:367–70.
3. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.