247 patients were evaluated for the long-term safety and efficacy of adjunctive brexpiprazole 2 mg/day in major depressive disorder.
Common included weight gain (33.2%), akathisia (23.5%), and nasopharyngitis (21.1%).
The mean increase in body weight from baseline to Week 52 was 4.2 kg, with 44.5% of patients experiencing weight gain of 7% or more.
Improvements in depression scores were observed, with a mean reduction in the score of 7.3 points at Week 52.
The overall response rate for depression symptoms was 41.3%, and the remission rate was 34.8% at Week 52.
No cases of tardive dyskinesia or treatment-related suicides were reported, suggesting a favorable safety profile.
Simplified
BACKGROUND AND OBJECTIVE: Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD.
METHODS: An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the (MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score.
RESULTS: In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment.
CONCLUSIONS: This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks.
STUDY REGISTRATION: ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).
Key numbers
-7.3
Mean Change in Total Score
Observed in patients receiving brexpiprazole.
44.5%
Weight Gain Incidence
Percentage of patients with weight gain ≥ 7% at any postbaseline visit.
26.7%
Discontinuation Rate Due to
Overall rate for patients receiving brexpiprazole.
Full Text
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M.K. reports consulting fees for this study from Otsuka Pharmaceutical Co., Ltd.; consulting fees from outside of this study from Sumitomo Pharma Co., Ltd., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Lundbeck Japan K.K., and Takeda Pharmaceutical Co., Ltd.; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Sumitomo Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Eli Lilly Japan K.K., MSD K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Shionogi & Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Lundbeck Japan K.K., Viatris Inc., Eisai Co., Ltd., Kyowa Pharmaceutical Industry Co., Ltd., and Ono Pharmaceutical Co., Ltd. M.S., K.K., K.I., Y.S., M.S., D.S., K.A., and Y.S. are full-time employees of Otsuka Pharmaceutical Co., Ltd. T.H. reports consulting fees for this study and honoraria for lectures from Otsuka Pharmaceutical Co., Ltd.
PubMed
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