Lactation and antipsychotic medication

A drug that is safe for use during pregnancy may not be safe for the nursing infant. Exposure to antipsychotic medication in breast milk markedly differs from exposure to antipsychotics by the fetus during pregnancy (118). The non-protein-bound (free) drug in the blood of the nursing mother enters breast milk at a rate that depends on its lipid solubility. The more fat-soluble the drug, the more of it enters. How much antipsychotic drug is present in breast milk at any one time depends mainly on the lipid concentration of the breast milk, which is different in foremilk and hindmilk and changes over time. An important factor is the temporal relationship between maternal drug ingestion and the time of nursing. The neonate's metabolic and excretory functions mature over time but are relatively underdeveloped at birth. Immature liver enzymes cannot detoxify drugs efficiently nor can the immature kidney competently eliminate drugs.

Metabolic pathways in existence at these early stages of development are not always the same ones that exist later, so the metabolites of a drug in the neonate may differ from those in the adult.

Relatively low protein binding in the infant increases the serum concentration of free drug that crosses into the brain, and all tissue concentrations are relatively high because of the small volume of distribution (118).

The literature suggests that infant serum concentrations of antipsychotics are largely unpredictable.

Clinical risk assessment is compromised by sparse data, as studies in breast-feeding women and their infants are ethically difficult to conduct.

A literature review (119) concluded that women who are vulnerable to postpartum exacerbation of psychiatric disorders are placed in a difficult position, often choosing to abandon the drugs they need to keep well or going to the other extreme and foregoing breast-feeding with all its known benefits to the infant and to the mother-child bond. These authors advise that parents be provided with all known available information and that the psychiatrist involve the pediatrician in monitoring the infant's exposure. Della-Giustina and Chow (120) offer the following advice to physicians advising nursing mothers:

1. Determine if medication is necessary.

2. Choose the safest drug available, that is, one that has been proven safe when administered directly to infants, has a low milk-to-plasma ratio, has a short half-life, has a high molecular weight, has high protein binding in maternal serum, is ionized in maternal plasma, and is relatively nonlipophilic.

3. Consult with the infant's pediatrician.

4. Advise the mother to take her medication just after she has breast-fed the infant or just before the infant's longest sleep period.

5. If there is a possibility that a drug may put the health of the infant at risk, monitor infant serum drug levels.