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Valproate Use in Children and Adolescents with Bipolar Disorder

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Abstract

This review aims to provide an update on valproate use in children and adolescents with bipolar disorder by summarising currently available clinical trials results. Guidelines for the treatment of type I bipolar disorder in children and adolescents, with or without psychotic features, recommend valproate, alone or in combination with an atypical antipsychotic, as a first-line treatment option; however, most randomised and open-label studies investigating valproate in paediatric populations have only evaluated a small number of participants. Therefore, the data from these studies need to be interpreted cautiously. A further complicating issue is the controversy surrounding the definition and diagnosis of bipolar disorders in this age group.

Data suggest that valproate may be particularly useful for patients whose symptoms have not been responsive to lithium, or as part of combination therapy. Evidence from randomised controlled trials show that valproate monotherapy is associated with a Young Mania Rating Scale (YMRS) response rate (percentage of patients with a reduction in YMRS score from baseline to endpoint of ≥50%) of 53%, while combination therapy with valproate plus quetiapine is associated with a YMRS response rate of 87%; however, placebo response rates were high, emphasising the need for caution when interpreting data from open-label trials.

At present, data supporting the efficacy and safety of mood stabilisers for the treatment of bipolar disorders in children and adolescents are limited; therefore, well designed, randomised controlled clinical studies are needed to identify and confirm the potential roles of valproate in children and adolescents with bipolar disorders, particularly in those with psychiatric co-morbidities. Furthermore, clinical studies are required to clarify the efficacy and tolerability profile of valproate in comparison with other agents used in paediatric and adolescent bipolar disorder.

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Acknowledgements

Editorial support for the preparation of this manuscript was provided by Luke Molloy, Wolters Kluwer Health Medical Communications. This assistance was funded by sanofi-aventis.

Dr Azorin receives, or has received, research support, and has acted as a consultant and/or served on a speaker’s bureau for Bristol-Myers Squibb, Janssen, Lilly, Lundbeck, Novartis, Pfizer and sanofi-aventis. Dr Findling receives, or has received, research support, and has acted as a consultant and/or served on a speaker’s bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Celltech-Medeva, Cypress Biosciences, Forest, GlaxoSmithKline, Johnson & Johnson, Lilly, New River, Novartis, Organon, Otsuka, Pfizer, sanofi-aventis, Sepracore, Shire, Solvay, Supernus Pharmaceuticals and Wyeth.

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Authors and Affiliations

  1. Hôpital de Sainte-Marguerite, 270 Boulevard de Sainte-Marguerite, 13274, Marseille, Cedex 09, France

    Jean Michel Azorin

  2. University Hospitals Case Medical Center, Cleveland, Ohio, USA

    Robert L. Findling

  3. Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA

    Robert L. Findling

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  1. Jean Michel Azorin
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Azorin, J.M., Findling, R.L. Valproate Use in Children and Adolescents with Bipolar Disorder. CNS Drugs 21, 1019–1033 (2007). https://doi.org/10.2165/00023210-200721120-00005

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