OBJECTIVES:  Brexpiprazole, a serotonin-dopamine activity modulator, was approved in 2015 in the United States for the treatment of schizophrenia and for use as adjunctive therapy in major depressive disorder (MDD). Characteristics of patients with MDD and their treatment adherence to brexpiprazole have not been previously studied in the long term care setting. METHODS:  The study used data from longitudinal long-term care pharmacy and outpatient medical databases. Patients aged ≥18 years, with a diagnosis of MDD, and who initiated brexpiprazole or an older atypical antipsychotic (AAPs; quetiapine, aripiprazole, or lurasidone) between 10-Jul-2015 and 3-Mar-2016 were included. Patient characteristics and prior use of antidepressants were measured in the 12 months prior to therapy initiation. Treatment adherence was measured by variable medication possession ratio (MPR_v) over a 3 month follow up among patients with ≥2 fills. RESULTS:  177 brexpiprazole, 14,261 quetiapine, 5,376 aripiprazole, and 1,244 lurasidone patients were identified. Mean age of brexpiprazole patients was 49±15.4 years (quetiapine: 64±18.8 years, aripiprazole: 57±18.4 years, lurasidone: 48±16.4 years). Anxiety was observed in 54% of brexpiprazole patients. 52% of brexpiprazole patients received their prescriptions from psychiatrists/psychologists compared to other AAPs (25% of quetiapine, 35% of aripiprazole, 45% of lurasidone). More brexpiprazole patients were previously treated with a selective serotonin reuptake inhibitor, and fewer were treated with a selective norepinephrine reuptake inhibitor compared to other AAPs. Mean MPR_v values were 94% in brexpiprazole, 94% in quetiapine, 93% in aripiprazole, and 92% in lurasidone. CONCLUSIONS:  This is the first study to describe the use of brexpiprazole for MDD in the long-term care setting. Patients treated with brexpiprazole were more often treated with a prior selective serotonin reuptake inhibitor and were more often treated by a specialist compared to patients on other AAPs. Adherence to brexpiprazole was similar to that of other AAPs.