Adjunctive Brexpiprazole Therapy Improves Outcomes in Individuals With MDD

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Researchers found data that showed, while the majority of patients with major depressive disorder left the study by week 26, in the long-term brexpiprazole is effective.

Adjunctive treatment with brexpiprazole was associated with improvement in efficacy and functional measures in individuals with major depressive disorder (MDD), according to an article published in the Journal of Clinical Psychopharmacology.

Adults with MDD were rolled over into the 52-week Orion study (later amended to 26 weeks), which sought to assess the long-term safety and tolerability of open-label treatment with adjunctive brexpiprazole (flexible dose 0.5 to 3 mg/day [d]). Previously, they had completed the Pyxis, Polaris, or Delphinus study, all of which were randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in MDD. Also, participants were not remitted on antidepressant treatment plus placebo in the parent studies and may or may not have been responders in parent studies.

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A total of 2944 adults were enrolled (1547 for 52 weeks, 1397 for 26 weeks). Of these participants, 1895 (64.4%) completed the study where they were titrated to brexpiprazole at the following doses: 0.5 mg/d during week 1, 1 mg/d during week 2, 0.5 to 2 mg/d during weeks 3 and 4, and 0.5 to 3 mg/d from week 5 onward. From the third week onward, doses were administered based on efficacy and tolerability, according to the investigator’s judgment. Antidepressant treatments used were escitalopram 10 and 20 mg/d; fluoxetine 20 and 40 mg/d; paroxetine controlled-release 37.5 and 50 mg/d; sertraline 100, 150, and 200 mg/d; duloxetine 40 and 60 mg/d; and venlafaxine extended-release, 75, 150, and 225 mg/d.

The treatment-emergent adverse events associated with antidepressant treatment plus brexpiprazole with an incidence of 5% or greater were weight increase (17.7%), somnolence (8%), headache (7.2%), akathisia (6.7%), increased appetite (6.3%), insomnia (6.3%), fatigue (6.1%), viral upper respiratory tract infection (5.4%), and anxiety (5.2%). Most treatment-emergent adverse events were mild or moderate in severity. The mean increase in body weight was 2.7 kg to week 26 and 3.2 kg to week 52; 25.8% of patients had a weight increase of 7% or greater at any postbaseline visit. There were no clinically relevant findings related to extrapyramidal symptoms, prolactin, lipids, or glucose. Patients’ symptoms and functioning showed continual improvement as assessed using the Clinical Global Impressions-Severity of Illness and Improvement scales, the Sheehan Disability Scale, and the Inventory of Depressive Symptomatology, Self-report.

Limitations of this study included the lack of a comparator for brexpiprazole, a relatively new drug.

Researchers concluded that that adjunctive treatment with brexpiprazole 0.5 to 3 mg/d was well tolerated for up to 52 weeks in MDD and “associated with continued improvement in efficacy measures and functional outcomes in the long term.”

Multiple authors declare affiliations with the pharmaceutical industry. Please refer to original reference for a complete list of authors’ disclosures.


Hobart M, Zhang P, Skuban A, et al. A long-term, open-label study to evaluate the safety and tolerability of brexpiprazole as adjunctive therapy in adults with major depressive disorderJ Clin Psychopharmacol. 2019;39(3):203-209.