VIENNA (FRONTLINE MEDICAL NEWS) – Adjunctive brexpiprazole in patients with an inadequate response to antidepressant monotherapy for major depressive disorder resulted in clinically meaningful improvement in multiple aspects of functional impairment, including cognitive dysfunction, in three open-label exploratory studies, Ross A. Baker, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Clinician-rated depressive symptoms also showed significant improvement once brexpiprazole (Rexulti) was on board, added Dr. Baker of Otsuka Pharmaceutical in Princeton, N.J.

The improvement in depressive symptoms was to be expected because the Food and Drug Administration has approved brexpiprazole as adjunctive therapy to antidepressants for treatment of major depression on the strength of pivotal trials showing a significant reduction in Montgomery-Asberg Depression Rating Scale ( MADRAS ) scores.

But fatigue and cognitive impairment are another matter. They are now recognized as core aspects of major depression. Even after patients’ depressive symptoms have gone into remission, lingering cognitive dysfunction often impairs performance at work or school, social life, and family/home life. Antidepressants don’t improve this depression-related cognitive impairment. This was the impetus for the three open-label exploratory studies, which addressed these common problems of functional disability and cognitive impairment in different populations with major depressive disorder. The target dose of brexpiprazole in all three studies was 2 mg per day in addition to whatever antidepressant medication patients were already on.

One 12-week study included 47 young patients working at a job or in school. Their mean baseline score on the Sheehan Disability Scale (SDS) was 6.5; a score of 5 or more on the 0-10 scale indicates significant functional impairment in the three domains covered by the SDS: home responsibilities, social life, and work or school performance.

After 12 weeks of adjunctive brexpiprazole, the patients’ mean SDS score had improved by 3.7 points. The improvement was significant across all three domains in this study, as well as in the other two open-label studies.

Patients also demonstrated significant improvement on the Cognitive and Physical Functioning Questionnaire (CPFQ), a self-rated scale that addresses cognitive impairment and executive function. The CPFQ consists of seven items, each scored 1-6, with a higher score indicating worse function in that domain. After 12 weeks on adjunctive brexpiprazole, the young patients experienced a mean 8.1-point improvement from a baseline CPFQ score of 26.1.

Another study included 37 patients with prominent anxiety as a feature of their major depressive disorder. Over the course of 6 weeks of treatment, their mean SDS score improved by 3.6 points from a baseline of 6.5. Also, their CPFQ score fell by 9.9 points from a baseline of 29.3.

The third study involved 61 patients who had switched antidepressants after an inadequate response. After 6 weeks on adjunctive brexpiprazole, their mean SDS score improved from 6.3 to 3.2, and their CPFQ dropped by 9.9 points from a baseline of 29.3 points.

Increased energy and alertness were commonly reported by participants in all three studies.

MADRS scores improved by a mean of 18.1 points from 28.3 points at baseline in the youth study, by 19.8 points from a baseline of 30.1 in the high-anxiety group, and by 17.3 points from a baseline of 29.6 in the study of patients who’d switched antidepressants.

These exploratory studies were sponsored by Otsuka Pharmaceutical. Dr. Baker is a company employee.

Brexpiprazole also is FDA-approved for treatment of schizophrenia.


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