Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Objective: Evaluate the efficacy and safety of adjunctive aripiprazole versus placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an incomplete response to ≥1 historical ADT and one prospective ADT. Methods: The study comprised a 7 to 28-day screening phase, an 8-week prospective treatment phase and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (HAM-D17 Total score ≥18) received escitalopram, fluoxetine, paroxetine CR, sertraline or venlafaxine XR, each with single-blind, adjunctive placebo. Patients with an incomplete response were then randomized to either continued adjunctive placebo (n=178) or adjunctive aripiprazole 2–20mg (n=184). Primary efficacy endpoint was the mean change in MADRS Total score from end of prospective treatment to end of randomized treatment (Week 14, LOCF). Results: 178 Mean MADRS change was significantly greater with adjunctive aripiprazole versus adjunctive placebo (-8.8 vs. -5.8; p<0.001). Adverse events occurring in ≥10% of patients with either adjunctive placebo or adjunctive aripiprazole groups were: akathisia (4.5 vs. 23.1%); headache (10.8 vs. 6.0%); restlessness (3.4 vs. 14.3%). Incidence rates of adverse events leading to discontinuation were low in both groups (adjunctive placebo: 1.7% vs. aripiprazole 2.2%). Weight gain ≥7% was seen in 1.2% and 7.1% of adjunctive placebo- and aripiprazole-treated patients, respectively.