title: Double-blind, randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder.
abstract: BACKGROUND
  This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00194077.
authors.affiliation: Department of Psychiatry, University Hospitals, Case Medical Center, Cleveland, OH 44106, USA. robert.findling@uhhospitals.org
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.forename: Nora K
authors.initials: NK
authors.lastname: McNamara
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Stansbrey
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Wynbrandt
authors.forename: Clara
authors.initials: C
authors.lastname: Adegbite
authors.forename: Brieana M
authors.initials: BM
authors.lastname: Rowles
authors.forename: Christine A
authors.initials: CA
authors.lastname: Demeter
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Frazier
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole