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.


BACKGROUND
ClinicalTrials.gov identifier: NCT01942733.
Duke University Hospital, Durham, NC 27710. andrew.krystal@duke.edu.|Duke University Hospital, Durham, North Carolina, USA.
Andrew D
AD
Krystal
H. Lundbeck A/S, Valby, Denmark.
Aurélia
A
Mittoux
H. Lundbeck A/S, Valby, Denmark.
Peter
P
Meisels
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Ross A
RA
Baker
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D018490:Serotonin Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012893:Sleep Wake Disorders / Q000150:complications / Q000188:drug therapy*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D018491:Dopamine Agonists; D015363:Quinolones; D018490:Serotonin Agents; D013876:Thiophenes; C000591922:brexpiprazole