Objective: This randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3 mg/day) and flexible dose (3-15 mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT). Method: During an 8-week prospective treatment phase, patients experiencing a major depressive episode received clinicians' choice of ADT. Subjects with inadequate response to ADT were randomized to receive adjunctive

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... t with placebo (n¼195), fixed dose aripiprazole (n¼ 197) or flexible dose aripiprazole (n¼194) for 6 weeks. The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of prospective treatment (baseline) to the end of randomized treatment. Results: More than 90% of patients in all treatment groups completed the 6-week double-blind treatment phase. Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole (À 10.5 and À 9.6, respectively) than with placebo (À 7.4). Aripiprazole was well tolerated. The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6 * 10 allele in Asian populations. Limitations: Six weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole. Exclusion of patients with established medical comorbidities does not reflect real-world practice. Conclusions: Aripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT. Clinical trials registration: ClinicalTrials.gov identifier NCT00876343.