Rational antipsychotic polypharmacy in psychotic and bipolar disorders: A focus on D2 receptor partial agonists

Aripiprazole, brexpiprazole, and cariprazine have a unique pharmacology as demonstrated by their high affinity to the dopamine type-2 receptor (ie, D2 receptor). These agents may be preferred over others for the treatment of psychotic and bipolar disorders due to their lower incidence of movement disorders and sedation. When prescribed adjunctively to full antagonist agents, partial agonist antipsychotics can mitigate adverse effects such as hyperprolactinemia. However, their high affinity for the D2 receptor may interfere with the efficacy of full antagonist antipsychotics when used in combination. Some partial agonists may be less preferred in particular patient scenarios based on their demonstrated clinical efficacy. Three illustrative patient cases highlight clinical pearls related to the safe and effective use of antipsychotic polypharmacy involving partial agonist antipsychotics.