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. The small amount of moclobemide, a new reversible monoamine oxidase inhibitor, excreted into breast milk is unlikely to be hazardous to suckling infants. The amount of trazodone that a suckling infant would ingest is less than 1% of the weight-adjusted maternal dose. Data on fluvoxamine and on fluoxetine are limited. However, it is unlikely that mothers receiving fluoxetine will be able to breast feed safely. Higher concentrations of phencyclidine in breast milk than in plasma, the potential for accumulation of cannabinoids, the lack of information on excretion of diamorphine (heroin) into milk, and the potential high sensitivity of the neonate to morphine, despite a low bioavailability, imply that mothers using these drugs should not breast feed. The potential long term effects of psychoactive substances on the psychomotor and mental development of the infant are unknown. The deleterious effects of maternal drug use via breast feeding should be investigated, as postnatal exposure might be associated with a decreased motor development long beyond the postnatal period.