ARTICLES
A Pilot Controlled Trial of Topiramate for Mania in Children and Adolescents With Bipolar Disorder

https://doi.org/10.1097/01.chi.0000159151.75345.20Get rights and content

ABSTRACT

Objective:

To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I.

Method:

This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement.

Results:

Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n = 29, 52%) or placebo (n = 27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p = .003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (−14.9 versus −5.9, p = .048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia.

Conclusions:

Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.

Section snippets

METHOD

This 4-week, prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group investigation was designed to enroll approximately 230 subjects. When topiramate monotherapy did not demonstrate superiority over placebo in acutely manic hospitalized adults with BPD (Powers et al., 2004), the trial was discontinued before enrollment was completed. This decision was made by the study sponsor in conjunction with an expert panel of advisors. The study was initially designed to

Subject Disposition and Baseline Characteristics

Of 77 children and adolescents screened, 56 were randomly assigned to treatment and were included in the efficacy and safety analyses (Fig. 1). Twenty-four (89%) and 21 (72%) subjects completed placebo and topiramate treatment, respectively (Fig. 1). One subject in the placebo group completed treatment but did not provide efficacy data for day 28, whereas one subject in the topiramate group discontinued treatment on day 26 but provided efficacy data for the final visit; thus, efficacy data were

DISCUSSION

The preliminary results of this study are inconclusive because of the early termination of the trial leading to only modest statistical power to detect between-group differences. The study originally was designed to treat 230 children and adolescents with topiramate or placebo for 28 days, but it was discontinued after only 56 subjects were enrolled because topiramate monotherapy did not demonstrate superiority over placebo in other trials of acutely manic hospitalized adults with BPD (Powers

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    Presented in part at the American College of Neuropsychopharmacology 42nd Annual Meeting, San Juan, PR, December 8, 2003.

    This study was supported by a grant from Johnson & Johnson Pharmaceutical Research & Development, LLC. The authors thank Robert Kowatch for standardizing raters for psychometric testing, Li-Joy Wang for assistance with statistical analyses, Jonathan Latham for assistance in preparing the manuscript, and Alan Unis for assistance with protocol development. The authors acknowledge contributions from the following study consultants and investigators: Valerie Arnold, Memphis; Charles Bailey, Orlando, FL; Mark Bangs, Indianapolis; Jeffrey Blumer, Cleveland; Sharon Cain, Kansas City, KS; Gabrielle Carlson, Stony Brook, NY; Kiki Chang, Stanford, CA; Joseph Haraszti, Cerritos, CA; Arnold Hartman, West Palm Beach, FL; Willis Holloway, Oklahoma City; Alan Jacobson, Hollywood, FL; Vivian Kafantaris, Glen Oaks, NY; Alain Katic, Bellaire, TX; Arifula Khan, Bellevue, WA; Robert Kowatch, Cincinnati; Adam Lowy, Washington, DC; Morteza Marandi, Cerritos, CA; William Murphy, Overland Park, KS; Steven Pliszka, San Antonio, TX; Michael Plopper, San Diego; Sohail Punjwani, North Miami, FL; Joachim Raese, Riverside, CA; Adelaide Robb, Washington, DC; David Sack, Cerritos, CA; Russell Scheffer, Dallas; Scott Segal, North Miami, FL; J. Stone, Austin, TX; Tram Tran-Johnson, San Diego; Himanshu Upadhyaya, Charleston, SC; Amit Vijapura, Jacksonville, FL; Karen Wagner, Galveston, TX; Elizabeth Weller, Merion Station, PA; Craig Wronski, Pico Rivera, CA; Kashinath Yadalam, Lake Charles, LA.

    Disclosure: Dr. DelBello has received research support, speaker honoraria, and/or consulting fees from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Ortho-McNeil, Pfizer, and Shire. Dr. Findling has received research support, speaker honoraria, and/or consulting fees from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Celltech-Medeva, Forest, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, New River, Novartis, Otsuka, Pfizer, Shire, Solvay, and Wyeth. Drs. Kushner, Wang, Olson, and Rosenthal and Ms. Capece are currently employees of Ortho-McNeil Pharmaceutical Inc. Dr. Fazzio is a former employee of Ortho-McNeil Pharmaceutical Inc.

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