Aripiprazole appears to be effective as adjunct therapy for adults whose major depressive disorder responds inadequately to antidepressant medication, according to study results presented at the annual meeting of the American Psychiatric Association.

The addition of aripiprazole to antidepressant therapy resulted in significant improvement in the primary endpoint, the Montgomery- Asberg Depression Rating Scale (MADRS) total score.

"Investigational studies are important because many patients with major depressive disorder do not achieve adequate symptom response," said study investigator Arif Khan, MD, 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."

The double-blind, randomized, placebo-controlled, multi-center, six-week study enrolled adults with major depressive disorder who had a documented inadequate response to one or more antidepressant medication. After a 7- to 28-day screening phase, patients underwent an 8-week prospective treatment phase with one antidepressant plus single-blind placebo to confirm the inadequate response to medication. Antidepressants 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 6-week randomized treatment phase during which they continued their antidepressant and added adjunctive placebo or aripiprazole (2-20 mg/day) in double-blinded fashion.

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 the MADRS total score, which can range from 0 (no symptoms) to 60 points (most severe symptoms). Some 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 significantly greater reduction in MADRS Total Score compared with placebo (-8.8 vs. -5.8 points).

The discontinuation rate due to an adverse event for adults taking aripiprazole was 3.3 percent compared with 2.3 percent for placebo. The most common adverse events in the aripiprazole and 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).