Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations.
The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)
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Département de Pharmacologie Clinique Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Université René Descartes, Paris, France.
Rey
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Matheson
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D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D000928:Antidepressive Agents / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D001940:Breast / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D007231:Infant, Newborn; D007774:Lactation / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism*; D009294:Narcotics / Q000493:pharmacokinetics; D011597:Psychomotor Performance / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002491:Central Nervous System Agents; D006993:Hypnotics and Sedatives; D009294:Narcotics