Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study).
OBJECTIVE
This randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3mg/day) and flexible dose (3-15 mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT).


METHODS
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 treatment with placebo (n=195), fixed dose aripiprazole (n=197) or flexible dose aripiprazole (n=194) 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 (-10.5 and -9.6, respectively) than with placebo (-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.


CONCLUSIONS
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.
International University of Health and Welfare, Otawara, Tochigi, Japan. Electronic address: kamijima@kitanet.ne.jp.
Kunitoshi
K
Kamijima
Teruhiko
T
Higuchi
Jun
J
Ishigooka
Tetsuro
T
Ohmori
Norio
N
Ozaki
Shigenobu
S
Kanba
Toshihiko
T
Kinoshita
Tsukasa
T
Koyama
D000328:Adult; D017109:Akathisia, Drug-Induced / Q000209:etiology; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068180:Aripiprazole; D044466:Asian People; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole
Aripiprazole; Japanese; Major depressive disorder; antipsychotic; augmentation therapy