The preclinical discovery and development of brexpiprazole for the treatment of major depressive disorder.

INTRODUCTION: Brexpiprazole is the most recently approved second-generation antipsychotic, which is used as adjunctive therapy to antidepressants for treating major depressive disorder (MDD) with inadequate response. Brexpiprazole shares pharmacological similarities with other second-generation antipsychotics, especially aripiprazole. Area covered: This review provides a detailed overview of the pre-clinical studies of brexpiprazole, followed by a summary of its clinical studies, and a comparison with other antipsychotics in MDD. Brexpiprazole is superior to placebo in reducing depressive symptoms of patients who have had an inadequate response to a standard antidepressant treatment. The efficacy of brexpiprazole is comparable to aripiprazole and quetiapine-XR, but brexpiprazole has demonstrated a lower risk for akathisia than aripiprazole and a lower risk for somnolence than quetiapine-XR. Expert opinion: Given that different studies have used different criteria to define 'treatment-resistance' or 'inadequate-response', an accurate comparison of the efficacy and safety of brexpiprazole with other antipsychotics is difficult. Preclinical data supports the premise that the antidepressant-like effects of antipsychotics are mainly due to their ability to modulate/regulate the monoamine system. Therefore, antipsychotics with similar pharmacodynamic properties like brexpiprazole could also take the 'me too' approach to treating MDD.