Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

AIMS: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. METHODS: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression-Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

Randomized, double-blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder.

AIM: This study compared the efficacy and safety of aripiprazole/sertraline combination (ASC) and placebo/sertraline combination (PSC) in patients with major depressive disorder (MDD) who showed an inadequate response to sertraline 100 mg/day. METHODS: The study comprised a screening period, an 8-week prospective treatment (single-blind sertraline 25-100 mg/day) period, and a 6-week double-blind treatment period. Patients with DSM-5-defined MDD were enrolled. Following the prospective treatment, non-responders were randomly assigned to the ASC group (aripiprazole 3-12 mg/day/sertraline 100 mg/day) or the PSC group (sertraline 100 mg/day). The primary efficacy end-point was the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks. RESULTS: A total of 412 patients were randomly assigned to either the ASC group (n = 209) or the PSC group (n = 203). Mean change in MADRS total score was significantly greater in patients with ASC than PSC (-9.2 vs -7.2; P = 0.0070). Treatment-emergent adverse events (TEAE) that occurred in ≥10% of patients with ASC versus PSC were nasopharyngitis (13.4% vs 11.3%) and akathisia (12.9% vs 3.4%). All TEAE reported in the ASC group were mild or moderate in severity. Rates of discontinuations due to TEAE were low in both the ASC (1.9%) and PSC (1.5%) groups. There were no notable issues in safety assessments in the ASC group compared with the PSC group. CONCLUSION: In patients with MDD who showed an inadequate response to treatment with sertraline 100 mg/day, ASC was efficacious and well tolerated.