Double-blind, randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder

Robert L. Findling, Eric A. Youngstrom, Nora K. McNamara, Robert J. Stansbrey, Jaime L. Wynbrandt, Clara Adegbite, Brieana M. Rowles, Christine A. Demeter, Thomas W. Frazier, Joseph R. Calabrese

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Background: This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders. Method: Outpatients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder (I, II, not otherwise specified, cyclothymia) were eligible to receive up to 16 weeks of open-label treatment with aripiprazole (phase 1). Patients were randomized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization (phase 2). During phase 2, patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo. The primary outcome measure for phase 2 was time to discontinuation due to a mood event. Results: Patients were recruited between May 2004 and November 2008. Following phase 1, in which 96 patients received aripiprazole, 30 patients (mean age = 7.1 years) were randomly assigned to continue aripiprazole and 30 patients (mean age = 6.7 years) were randomly assigned to placebo. The mean (SD) dose of aripiprazole prior to randomization for these patients was 6.4 (2.1) mg/d. Patients randomly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event (6.14 median weeks, SE ± 11.88 weeks; P = .005) and discontinuation for any reason (including mood events) (4.00 median weeks, SE ± 3.91 weeks; P = .003) than those randomly assigned to placebo (mood event, 2.29 median weeks, SE ± 0.38 weeks; any reason, 2.00 median weeks, SE ± 0.31 weeks). Regardless of random assignment, both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks (15/30 [50%] for aripiprazole; 27/30 [90%] for placebo), suggesting a possible nocebo effect (ie, knowledge of possibly switching from active medication to placebo increasing concern about relapse). The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain (n = 10, 33%), increased appetite (n = 9, 30%), and headaches (n = 9, 30%). Conclusions: Despite the possibility of a nocebo effect, these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole. Trial Registration: Identifier: NCT00194077.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalJournal of Clinical Psychiatry
Issue number1
StatePublished - Jan 2012
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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