Adjunctive Brexpiprazole for Patient Life Engagement in Major Depressive Disorder: A Canadian, Phase 4, Open-Label, Interventional Study: Brexpiprazole d'appoint pour l'engagement dans la vie des patients souffrant de trouble dépressif majeur: une étude interventionnelle canadienne ouverte de phase 4

Objectives To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. Methods An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1–2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5–2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. Results Of 122 enrolled patients, 120 (98.4%) were treated (mean SD dose: 1.2 0.4 mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR 10 Life Engagement subscale score (baseline mean SD: 16.1 4.7; change 95% confidence interval: −8.11 −9.34, −6.88; p < 0.001) and IDS-SR total score (baseline mean SD: 41.3 9.8; change 95% confidence interval: −17.38 −20.08, −14.68; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue ( n = 13, 10.8%), headache ( n = 13, 10.8%), insomnia ( n = 12, 10.0%), nausea ( n = 9, 7.5%), tremor ( n = 8, 6.7%), and weight increase ( n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean ( SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. Conclusions Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. Clinical Trial Registration ClinicalTrials.gov identifier: NCT04830215.