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Aripiprazole in Children and Adolescents With Bipolar Disorder Comorbid With Attention-Deficit/Hyperactivity Disorder: A Pilot Randomized Clinical Trial
Silzá Tramontina, MD; Cristian P. Zeni, MD; Carla R. Ketzer, MD; Gabriel F. Pheula, MD; Joana Narvaez, BA; and Luis Augusto Rohde, MD, PhD
Objective: To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder (ADHD).
Method: Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710). Those with this comorbidity who were acutely manic or in mixed states were randomly assigned in a 6-week double-blind, placebo-controlled trial to aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental Version (CMRS-P), the Children's Depression Rating Scale-Revised, the Kutcher Adolescent Depression Scale, and adverse events. The trial was conducted at the Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, from January 2005 to November 2007.
Results: The group receiving aripiprazole showed a significantly greater reduction in YMRS scores (P = .02, effect size [ES] = 0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28) from baseline to endpoint than the placebo group. In addition, higher rates of response (P = .02) and remission (P = .01) were found for the aripiprazole group. No significant between-group differences were found in weight, ADHD symptoms, and depressive symptoms. Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea.
Conclusion: Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain. No significant treatment effect in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD.
Trial registration: clinicaltrials.gov Identifier: NCT00116259
(J Clin Psychiatry 2009;70(5):756-764. Online Ahead of Print April 21, 2009. doi:10.4088/JCP.08m04726)
Received September 20, 2008; accepted January 27, 2009. From the Juvenile Bipolar Disorder Outpatient Program (ProCAB), Division of Child and Adolescent Psychiatry, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
This work was supported completely by research grants to the ADHD Outpatient Program at the Hospital de Clínicas de Porto Alegre from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) (Grant 471761/03-6), and Hospital de Clínicas de Porto Alegre (GPPG 03-325), and Bristol-Myers Squibb. Aripiprazole was provided by Bristol-Myers Squibb without restrictions.
Presented in part at the 6th annual National Institute of Mental Health Pediatric Bipolar Disorder Conference; March 2008; Cambridge, Massachusetts.
The authors thank Aline Sokolovsky, BA, and Roberta Coelho, BA, for neuropsychological assessment and Clarissa Paim, BA, for administrative assistance. All acknowledged personnel are from the Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Mss Sokolovsky, Coelho, and Paim report no financial or other relationship relevant to the subject of this article.
Dr Tramontina has been a member of the speakers/advisory board for Abbott for the past year. Dr Rohde was on the speakers bureaus and/or acted as consultant for Eli Lilly, Janssen-Cilag, and Novartis in the last 3 years. Currently, his only industry-related activity is taking part of the speakers bureau/advisory boards for Eli Lilly and Novartis (less than US$ 10,000 per year and reflecting less than 5% of his gross income per year). The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Abbott, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Novartis, and Shire. Drs Zeni and Pheula received travel awards from Abbott to attend a national meeting. Dr Ketzer and Ms Narvaez report no additional financial or other relationship relevant to the subject of this article.
Corresponding author and reprints: Luis Augusto Rohde, PhD, Servišo de Psiquiatria da Infância e Adolescência, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul, Brazil 90035-903 (e-mail: email@example.com).