Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled, 52-Week Randomized Withdrawal Study.
To evaluate efficacy, safety, and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) as maintenance treatment for bipolar I disorder (BP-I).



In a double-blind, placebo-controlled, 52-week randomized withdrawal study conducted from August 2012 to April 2016, patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then randomized to AOM 400 or placebo. The primary end point was time from randomization to recurrence of any mood episode. Other end points included proportion of patients with recurrence of any mood episode and recurrence by mood episode type.



Of 266 randomized patients, 64 (48.1%) of 133 in the AOM 400 group and 38 (28.6%) of 133 in the placebo group completed the study. AOM 400 significantly delayed the time to recurrence of any mood episode compared with placebo (hazard ratio: 0.45; 95% CI, 0.30 to 0.68; P < .0001). Significantly fewer patients (P < .0001) experienced recurrence of any mood episode with AOM 400 (35/132; 26.5%) compared with placebo (68/133; 51.1%), with the effects observed predominantly on manic episodes (P < .0001). Patients were not depressed at study entry, and between-group differences in depressive episodes were not significant (P < .864). The treatment-emergent adverse events (incidence > 5%) that were reported at higher rates with AOM 400 than placebo were weight increase, akathisia, insomnia, and anxiety.



AOM 400 delayed the time to and reduced the rate of recurrence of mood episodes and was generally safe and well tolerated. These findings support the use of AOM 400 for maintenance treatment of BP-I.



ClinicalTrials.gov identifier: NCT01567527.
University Hospitals Case Medical Center, 10524 Euclid Ave, Cleveland, OH 44106. joseph.calabrese@uhhospitals.org.|University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Joseph R
JR
Calabrese
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Raymond
R
Sanchez
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Na
N
Jin
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Joan
J
Amatniek
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Kevin
K
Cox
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Brian
B
Johnson
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Pamela
P
Perry
H. Lundbeck A/S, Valby, Denmark.
Peter
P
Hertel
H. Lundbeck A/S, Valby, Denmark.
Pedro
P
Such
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Phyllis M
PM
Salzman
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Robert D
RD
McQuade
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
Margaretta
M
Nyilas
Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
William H
WH
Carson
D000284:Administration, Oral; D000328:Adult; D000339:Affect / Q000187:drug effects; D000068180:Aripiprazole / Q000008:administration & dosage* / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D000068180:Aripiprazole