Second-Generation Antipsychotics During the Lactation Period A Comparative Systematic Review on Infant Safety

Objective: This review examined the safety of second-generation antipsychotics (SGAs) in exposed breastfed infants. Methods: PubMed was searched for English language reports between January 1, 1990, to June 30, 2015, by using combinations of the key words breastfeeding, lactation, postpartum period, puerperium, antipsychotics, second-generation antipsychotics, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, amisulpride, clozapine, asenapine, lurasidone, and iloperidone. Case reports, case series, and prospective or cross-sectional studies including relevant data such as relative infant dose (RID), milk-to-plasma ratio (M/P ratio), infant drug plasma levels, and adverse events were identified. Results: A total of 37 relevant reports were examined. These reports included a total of 206 infants exposed to olanzapine (n = 170), quetiapine (n = 14), risperidone/paliperidone (n = 8), clozapine (n = 6), aripiprazole (n = 4), ziprasidone (n = 2), and amisulpride (n = 2). Approximately half of the available data on the M/P ratio, RID, and infant drug plasma levels included olanzapine. Relatively adequate reports suggest that olanzapine has low RID values. Limited reports suggest low RID values for quetiapine and ziprasidone, moderate RID values for risperidone/paliperidone and aripiprazole, and high RID values for amisulpride. Antipsychotic levels were undetectable in the plasma of most of the exposed infants. Other than clozapine, adverse events were rarely reported in infants exposed to SGAs. Conclusions: The current data suggest that SGAs seem to be relatively safe in the exposed breastfed infants for short-term usage. However, additional studies, in particular for antipsychotics other than olanzapine, examining short-term and especially long-term effects of SGAs on the breastfed infants are required.