Neuroleptic drugs in breast-milk: a study of pharmacokinetics and of possible adverse effects in breast-fed infants

Psychol Med. 1998 Jan;28(1):81-91. doi: 10.1017/s0033291797005965.

Abstract

Background: Very little is known about the pharmacokinetics of neuroleptic drugs in breast-feeding mothers and their infants or about possible adverse effects in the infants.

Method: Twelve mothers who breast-fed their infants were prescribed haloperidol, chlorpromazine or trifluoperazine. Two methods, enzyme immunoassay (EIA) and high performance liquid chromatography (HPLC) were used to assay these drugs in samples from mothers, but infants' samples were assayed only by the more sensitive EIA. Repeated clinical and developmental assessments of the breast-fed infants were carried out up to 30 months of age. The control subjects were 18 bottle-fed infants whose mothers were also prescribed neuroleptic or mood-stabilizing drugs.

Results: The total concentrations of neuroleptic drugs and their principal metabolites in maternal plasma were correlated with concentrations in fore-milk. Infants were ingesting up to 3% of the maternal daily dose per kg body weight and small amounts of the drugs were detected in infants' plasma and urine. Concentrations of haloperidol in the adult range were found in plasma from 2 of 5 infants assayed by EIA but there was no evidence of any acute or delayed adverse effects. Three other breast-fed infants whose mothers were prescribed both haloperidol and chlorpromazine showed a decline in their developmental scores from the first to the second assessment at 12-18 months.

Conclusion: More extensive longitudinal studies are needed but, in the meantime, there appears to be grounds for caution if breast-feeding mothers are prescribed doses of single or two neuroleptic drugs at the upper end of their recommended ranges.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacokinetics*
  • Antipsychotic Agents / therapeutic use
  • Bottle Feeding
  • Breast Feeding / adverse effects*
  • Child Development / drug effects
  • Chlorpromazine / blood
  • Chlorpromazine / pharmacokinetics
  • Chlorpromazine / therapeutic use
  • Chromatography, High Pressure Liquid
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Haloperidol / blood
  • Haloperidol / pharmacokinetics
  • Haloperidol / therapeutic use
  • Humans
  • Imipramine / blood
  • Imipramine / pharmacokinetics
  • Imipramine / therapeutic use
  • Immunoenzyme Techniques
  • Infant, Newborn / blood*
  • Maternal Exposure
  • Maternal-Fetal Exchange*
  • Milk, Human / chemistry*
  • Milk, Human / metabolism
  • Pregnancy
  • Psychotic Disorders / blood
  • Psychotic Disorders / drug therapy
  • Puerperal Disorders / blood
  • Puerperal Disorders / drug therapy

Substances

  • Antipsychotic Agents
  • Haloperidol
  • Imipramine
  • Chlorpromazine