EXCRETION OF PSYCHOACTIVE-DRUGS INTO BREAST-MILK - PHARMACOKINETIC PRINCIPLES AND RECOMMENDATIONS

The postpartum period is a time of great physical and emotional change s. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whethe r women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on pas sive diffusion of the unionised unbound drug. Passive diffusion is aff ected mainly by the drug disposition in lactating mothers, by the phys icochemical properties of the molecule and by the protein and lipid co ntents of breast milk. Indeed, breast milk can be considered as a comp artment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropi c drugs. Generally there does not seem to be any contraindication to b reast feeding after a single dose, provided the dose administered is r elatively low. If higher doses are to be used or long term administrat ion is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basi s of the average concentration of phenobarbital (phenobarbitone) in mi lk, breast feeding is not recommended. For glutethimide, breast feedin g would appear to be safe for the infant when a single dose is taken o ccasionally. 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 nonp henothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not a lways considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clo mipramine should be contraindicated during breast feeding depends on t he concentration of active metabolites in breast milk, and this has no t yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendati ons are made, more infants should be studied. The available data sugge st that the amount of doxepin and its metabolite in breast milk is sma ll. However, the metabolite of doxepin may accumulate in the infant wi th risk of sedation and respiratory depression; therefore, an alternat ive antidepressant should be selected for breast feeding mothers. The small amount of moclobemide, a new reversible monoamine oxidase inhibi tor, 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 fluvoxam ine and on fluoxetine are limited. However, it is unlikely that mother s receiving fluoxetine will be able to breast feed safely. Higher conc entrations of phencyclidine in breast milk than in plasma, the potenti al for accumulation of cannabinoids, the lack of information on excret ion of diamorphine (heroin) into milk, and the potential high sensitiv ity of the neonate to morphine, despite a low bioavailability, imply t hat mothers using these drugs should not breast feed. The potential lo ng term effects of psychoactive substances on the psychomotor and ment al development of the infant are unknown. The deleterious effects of m aternal drug use via breast feeding should be investigated, as postnat al exposure might be associated with a decreased motor development lon g beyond the postnatal period.