OBJECTIVES:  Brexpiprazole, a serotonin-dopamine activity modulator, was approved in 2015 in the United States for the treatment of schizophrenia and for use as an adjunctive treatment for major depressive disorder (MDD). The aim of the study was to describe patient characteristics, treatment history before adjunctive atypical antipsychotic (AAP) initiation, and adherence to brexpiprazole and older AAPs indicated for MDD (quetiapine, aripiprazole, and lurasidone). METHODS:  Prescription and medical history were obtained from longitudinal prescription and medical claims databases. Patients selected were ≥18 years of age with a diagnosis of MDD who initiated adjunctive brexpiprazole or other AAPs between 10-Jul-2015 and 31-Mar-2016. Patient characteristics and antidepressant use were measured in the 12 months before therapy initiation. Adherence was measured by variable medication possession ratio (MPR_v) during a 3 month follow up period in patients with ≥2 fills. RESULTS:  4,265 brexpiprazole, 88,063 quetiapine, 63,004 aripiprazole, and 11,462 lurasidone patients were identified. Mean age of brexpiprazole patients was 49±14.4 years (quetiapine: 54±16.7 years, aripiprazole: 49±15.7 years, lurasidone: 44±14.3 years). 55% of brexpiprazole patients had prior use of a selective serotonin reuptake inhibitor (quetiapine: 59%, aripiprazole: 58%, lurasidone: 54%), and 48% of brexpiprazole patients had prior use of a serotonin and norepinephrine reuptake inhibitor (SNRI) (quetiapine: 30%, aripiprazole: 38%, lurasidone: 33%) in the previous year. Among patients newly diagnosed with MDD, 19% of brexpiprazole, 11% of quetiapine, 12% of aripiprazole, and 12% of lurasidone patients had used ≥3 antidepressants prior to current therapy. Mean MPR_v was 90% in brexpiprazole, 89% in quetiapine, and 88% in aripiprazole and lurasidone. CONCLUSIONS:  Brexpiprazole patients were more often treated with a prior SNRI compared to other AAP patients. Brexpiprazole patients had used ≥3 prior antidepressants. Adherence to brexpiprazole was similar to that of other AAPs.