Objective: The Orion study (NCT01360866) evaluated the long-term safety, tolerability, and therapeutic effect of brexpiprazole (0.5–3 mg/day), as adjunct to antidepressant treatment, in adult patients with major depressive disorder (MDD).
Methods: Patients rolled over into this 52-week open-label study (amended to 26 weeks) from three randomized, double-blind, placebo-controlled Phase 3 studies. The primary outcome was the frequency and severity of TEAEs. Efficacy was assessed as a secondary objective using the CGI-S and CGI-I scales, SDS, and IDS-SR.
Results: 2,944 patients were enrolled (1,547 for 52 weeks; 1,397 for 26 weeks); 1,895 (64%) completed. The mean daily dose of adjunctive brexpiprazole at endpoint was 1.51 mg/day. Among patients who took at least one dose of brexpiprazole, the incidence of discontinuation due to TEAEs was 8.6%. TEAEs with an incidence of ≥5.0% were weight increased (17.7%), somnolence (8.0%), headache (7.2%), akathisia (6.7%), insomnia and increased appetite (6.3% each). Most TEAEs were mild or moderate in severity. The mean increase in body weight from baseline to Week 26 was 2.7 kg, and 3.2 kg to Week 52; 26.8% of patients had a weight increase ≥7% at any time during the study. Patients’ symptoms and functioning showed continual improvement, as measured by decreases in CGI-S, CGI-I, SDS and IDS-SR scores from baseline to Week 26 and further at Week 52.
Conclusions: In patients with MDD, adjunctive treatment with open-label brexpiprazole (0.5–3 mg/day) was generally well tolerated for up to 52 weeks. During this time, efficacy measures and functional outcomes continued to improve.