Drowsiness and poor feeding in a breast-fed infant: association with nefazodone and its metabolites

Ann Pharmacother. 2000 Nov;34(11):1269-72. doi: 10.1345/aph.10120.


Objective: To investigate whether adverse effects in a premature neonate could be attributed to nefazodone exposure via breast milk.

Case summary: The breast-fed white infant (female, 2.1 kg, 36 weeks corrected gestational age) of a 35-year-old woman (60 kg) taking nefazodone 300 mg/d was admitted to the hospital because she was drowsy, lethargic, unable to maintain normal body temperature, and was feeding poorly. A diagnosis of exposure to nefazodone via breast milk was considered only after other more likely diagnoses had been excluded. After breast feeding was discontinued, the infant's symptoms resolved slowly over a period of 72 hours. The maternal plasma and milk concentration-time profiles for nefazodone and its metabolites, triazoledione, HO-nefazodone, and m-chlorphenylpiperazine, were quantified by HPLC. The calculated infant dose for nefazodone and its active metabolites (as nefazodone equivalents) via the milk was only 0.45% of the weight-adjusted maternal nefazodone daily dose.

Discussion: Our data suggest a putative association between maternal nefazodone ingestion and adverse effects in a premature breast-fed neonate. The measured amount of drug exposure would normally be considered safe in a full-term infant. However, there was a temporal relationship between resolution of adverse effects in the infant and cessation of breastfeeding.

Conclusions: This case highlights the importance of individualizing the risk-benefit analysis for exposure to antidepressants in breast milk, especially when dealing with premature neonates.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / adverse effects*
  • Antidepressive Agents, Second-Generation / metabolism
  • Area Under Curve
  • Breast Feeding*
  • Depression, Postpartum / drug therapy*
  • Feeding Behavior / drug effects*
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Milk, Human / chemistry*
  • Piperazines
  • Sleep Stages / drug effects*
  • Triazoles / adverse effects*
  • Triazoles / metabolism
  • Triazoles / pharmacokinetics


  • Antidepressive Agents, Second-Generation
  • Piperazines
  • Triazoles
  • nefazodone