Effects of Adjunctive Brexpiprazole on Sleep Disturbances in Patients With Major Depressive Disorder: An Open-Label, Flexible-Dose, Exploratory Study

Background: Brexpiprazole is a serotonin-dopamine activity modulator. We evaluated the effects of adjunctive treatment with brexpiprazole on sleep disturbances in patients with DSM-IV-TR major depressive disorder (MDD) and inadequate response to antidepressant treatment.

Methods: This study was conducted between September 27, 2013, and August 19, 2014. Patients with inadequate response to antidepressant treatment and sleep disturbances continued treatment with their current antidepressant for 2 weeks. Patients still having inadequate response and sleep efficiency less than 85% measured by baseline polysomnography (PSG) received 8-week open-label treatment with their current antidepressant treatment and adjunctive brexpiprazole (target dose: 3 mg/d). Assessments included PSG recordings and scales of insomnia severity, depressive symptoms, and daytime alertness and functioning. Changes from baseline to week 8 were analyzed.

Results: Forty-four patients were treated. Improvements (P < .05) measured by PSG and Consensus Sleep Diary for Morning, respectively, were observed in sleep efficiency (10.4 and 15.4 percentage points), total sleep time (49.0 and 84.5 min), sleep onset latency (−19.7 and −42.6 min), wake-time after sleep onset (−26.4 and −48.0 min), and latency to persistent sleep (−24.9 min, PSG only). Insomnia Severity Index (ISI) total score was improved (−9.2), as was daytime sleepiness (−2.1) as measured by the Epworth Sleepiness Scale (ESS) total score and morning sleepiness (−9.2) as measured by the Bond-Lader Visual Analog Scale (all P < .05). Reaction time was slightly decreased (−0.2 sec−1) by treatment (P < .05). Depressive symptoms improved (Montgomery-Asberg Depression Rating Scale [MADRS]: −16.0 and Clinical Global Impressions—Severity [CGI-S]: −1.8), as did functioning (−8.4) assessed by the Massachusetts General Hospital—Cognitive and Physical Functioning Questionnaire (all P < .05). Improvements in depressive symptoms were dependent on sleep (as assessed by ISI) (P < .0001) and improvements in daytime alertness (as assessed by ESS) were dependent on improvements in ISI (P = .009). No new safety concerns were observed compared to previous brexpiprazole studies.

Conclusions: In patients with inadequate response to antidepressant treatment and sleep disturbances treated with adjunctive brexpiprazole, physiologic measures of sleep and daytime alertness were improved.

Trial registration: ClinicalTrials.gov identifier: NCT01942733