Dopamine Partial Agonists in Pregnancy and Lactation: A Systematic Review

Abstract

Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when breastfeeding assumes great importance. We set to investigate the use of dopamine partial agonists in pregnancy and lactation. Methods: On 23 June 2025, we used suitable strategies for identifying cases and studies of cariprazine, aripiprazole, brexpiprazole, dopamine partial agonists in pregnancy, perinatal period, and/or lactation on PubMed, CINAHL, PsycInfo/PsycArticles, Scopus, and ClinicalTrials.gov. We used the PRISMA Statement in developing our review. We included case reports and clinical studies. We excluded reports without pregnancy or focused on other drugs than the above. We reached consensus on eligibility with Delphi rounds among all authors. Results: Our searches produced 386 results on the above databases. We included 24 case reports/series and 15 studies. Most studies showed no negative pregnancy outcomes. There were serious concerns about the use of dopamine D₂/D₃ partial agonists during lactation. Conclusions: The use of dopamine partial agonists during pregnancy appears to be safe, but during breastfeeding they should be better avoided.

Keywords: aripiprazole; breastfeeding; brexpiprazole; cariprazine; dopamine D2/D3 partial agonists; lactation; perinatal period; pregnancy; puerperium.

Figure 1

Chemical structures of DAPAs (aripiprazole, brexpiprazole, and cariprazine).

Figure 2

Mechanism of action of dopamine partial agonists. Ideally, these drugs displace dopamine and antagonists from the D₂ group of dopamine receptors (D₂, D₃, and D₄), thus moderately enhancing the action of dopamine at this level. The consequence of this action in the site of origin of dopaminergic neurons that project to the cortex and the limbic system (ventral tegmental area {A10} and retrorubral area {A8}) is that dopamine synthesis and forwarding to the synapse is slowed down. The presynaptic action at the mesolimbic level ensues in smoothly modulating dopamine release, while the partial agonist activity partially counteracts the excess dopamine activity at that level, which is linked to production of positive symptoms, such as hallucinations and delusions. At the prefrontal cortical level, where there is a relative lack of dopamine autoreceptors, where the decreased baseline dopamine activity is believed to be related to intellectual numbness, lack of curiosity, and low drive for pleasurable activity, partial dopamine agonists increase the dopaminergic stimulation of these receptors, accounting for their efficacy against negative symptoms. Of course, this may only be wishful thinking.

Figure 3

PRISMA 2020 flowchart [45] of our search with reasons for exclusion.