Second-generation antipsychotics are common candidates for the adjunctive treatment of major depressive disorder and for the
treatment of schizophrenia. However, unmet needs remain in the treatment of both disorders. Considering schizophrenia, antipsychotics
are the most common treatment and have demonstrated good efficacy. Still, side effects of these treatments are commonly reported
and may impact adherence to the medication and functioning in patients with schizophrenia. Regarding major depressive disorder,
despite the availability of several classes of antidepressants, many patients do not achieve remission. Adjunctive treatment with
antipsychotics may improve clinical and functional outcomes.
Compared with dopamine D2 receptor antagonism that is exhibited by most antipsychotics, partial agonism may result in improved
outcomes in major depressive disorder and in schizophrenia. Aripiprazole, cariprazine, and brexpiprazole have partial agonism at the
dopamine D2 receptor and could potentially overcome limitations associated with D2 antagonism. The objectives of this review were (1)
to discuss the goal of treatment with second-generation antipsychotics in major depressive disorder and schizophrenia, and the clinical
factors that should be considered, and (2) to examine the short- and long-term existing data on the efficacy and safety of D2 receptor
partial agonists (aripiprazole, cariprazine, and brexpiprazole) in the adjunctive treatment of major depressive disorder and in the
treatment of schizophrenia.