Cariprazine in Human Milk

BACKGROUND: Cariprazine is a dopamine D2/D3 partial agonist approved for treatment-resistant depression, bipolar disorder (BD) and schizophrenia. Women with bipolar disorder face an increased risk of postpartum mania and psychosis, as childbirth often triggers episodes. While continuing cariprazine can be crucial for maternal well-being, limited data exist on its peripartum safety. The objective of this research is to assess the risk of infant exposure to maternal cariprazine via breast milk. METHODS: Breast milk samples were released from the InfantRisk Human Milk Biorepository from 5 lactating women who were taking cariprazine 1.5 to 4.5 mg daily, 4 of whom continued the drug since pregnancy. Timed samples were collected and analyzed using liquid chromatography-tandem mass spectrometry for cariprazine and its active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR). Infant risk was assessed by determining relative infant dose (RID%) and maternal reports of infant outcomes. RESULTS: Cariprazine and its metabolites were detectable in all participants' milk samples. Mean RID% was 1.23% for cariprazine, 0.09% for DCAR, and 1.22% for DDCAR, yielding a cumulative exposure of 2.54% RID; the highest individual dose-standardized RID was 3.99% (cumulative). Two mothers self-reported infant lethargy, one of which resolved after maternal dose reduction. CONCLUSIONS: Estimated infant exposure to cariprazine and its active metabolites falls below standard safety thresholds. However, reported infant adverse effects and the potential for metabolite accumulation due to DDCAR's long half-life necessitate further research to examine potential long-term adverse effects while breastfeeding, particularly in infants exposed to higher maternal doses. These findings represent the first empirical data on cariprazine during lactation and highlight the need for further studies, including pharmacokinetic modeling, to inform clinical guidance.