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Efficacy and safety of Aripiprazole as adjunctive therapy in major depressive disorder

May 22, 2007

In adults with major depressive disorder, adding aripiprazole to antidepressant therapy (ADT) resulted in significant improvement in the primary endpoint, the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. In this six-week, randomized, placebo-controlled study presented here at the 160th Annual Meeting of the American Psychiatric Association, the Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka Pharmaceutical Co., Ltd. atypical antipsychotic aripiprazole was added to antidepressants in patients who did not have an adequate response to ADT alone. (1)(Berman, 2007, APA Poster) These findings are from one of two completed studies evaluating adjunctive aripiprazole with ADT.

"Investigational studies are important because many patients with major depressive disorder do not achieve adequate symptom response," said study investigator Arif Khan, M.D., Medical Director, Northwest Clinical Research Center, Bellevue, Wash., and Adjunct Professor, Psychiatry, Duke University, Durham, N.C. "The findings from this study contribute more information about the potential use of add-on medications to antidepressant therapy in patients who inadequately respond to antidepressants alone."

Study Design and Findings

This double-blind, randomized, placebo-controlled, multi-center, six-week study enrolled adults diagnosed with major depressive disorder who had an inadequate response to one or more ADTs. After a seven to 28-day screening phase, adults in this study underwent an eight-week prospective treatment phase with one ADT plus single-blind placebo to confirm their inadequate response to ADT. The ADTs included escitalopram, fluoxetine, paroxetine controlled release, sertraline or venlafaxine extended release, dosed per label guidelines. A total of 362 adults with inadequate response then entered the six-week randomized treatment phase during which they continued their ADT plus double-blind adjunctive placebo or adjunctive aripiprazole (2-20 mg/day).

The primary efficacy endpoint was the mean change from baseline - the end of the prospective treatment phase - to the end of the randomized treatment phase in a standard measure called the MADRS Total Score, which can range from 0 (no symptoms) to 60 points (most severe symptoms). A reduction in MADRS Total Score represents improvement in depressive symptoms. Some of the secondary endpoints included Sheehan Disability Scale (SDS), MADRS-measured remission and response rates and Clinical Global Impression-Severity of Illness (CGI-S) score.

For the primary endpoint, the study showed that adults taking adjunctive aripiprazole had a greater reduction in MADRS Total Score from baseline compared to placebo (-8.8 vs. -5.8 points, p-value less than 0.001).

The discontinuation rate due to an adverse event for adults taking add-on aripiprazole was 3.3 percent and 2.3 percent for placebo. The most common adverse events in the add-on aripiprazole and add-on placebo groups, respectively, (greater than or equal to 5 percent and at least twice the incidence of placebo) were akathisia (23.1 percent vs. 4.5 percent), insomnia (7.7 percent vs. 2.3 percent), restlessness (14.3 percent vs. 3.4 percent), upper respiratory tract infection (8.2 percent vs. 4 percent), and blurred vision (6.6 percent vs. 1.7 percent).

Bristol-Myers Squibb