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Aripiprazole for the Treatment and Prevention of Acute Manic and Mixed Episodes in Bipolar I Disorder in Children and Adolescents: A NICE Single Technology Appraisal

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Abstract

As part of its single technology process, the National Institute for Health and Care Excellence (NICE) invited the manufacturers of aripiprazole (Otsuka Pharmaceutical Co. and Bristol Myers Squibb) to submit evidence of the clinical and cost effectiveness of aripiprazole for the treatment and prevention of acute manic and mixed episodes in bipolar I disorder in children and adolescents. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the manufacturers’ submission to NICE. The evidence, which was derived mainly from a double-blind, phase III, placebo-controlled trial of aripiprazole in patients aged 10–17 years, showed that aripiprazole performed significantly better than placebo in reducing mania according to the primary outcome measurement (the Young Mania Rating Scale at 4 weeks). Safety outcomes indicated that aripiprazole was significantly more likely to cause extrapyramidal symptoms and somnolence than placebo. The manufacturers also presented a network meta-analysis of aripiprazole versus other atypical antipsychotics commonly used to treat manic episodes (olanzapine, quetiapine and risperidone) to show that aripiprazole performed similarly to the comparator drugs in terms of efficacy and safety. Aripiprazole was demonstrated to perform better in safety outcomes of (1) less weight gain than olanzapine and quetiapine; and (2) less prolactin increase than olanzapine, quetiapine and risperidone. Results from the manufacturers’ economic evaluation showed that use of aripiprazole second-line dominated all of the other treatment strategies that were considered. However, there was considerable uncertainty in this result, and clinical advisors indicated that the actual treatment strategy employed in practice is likely to be dependent upon the patient’s characteristics. The ERG demonstrated that if this personalised medicine resulted in improved cost effectiveness for any of the other treatment strategies, then they had the potential to dominate use of aripiprazole second-line. In conclusion, whilst a strategy including aripiprazole appeared to be cost effective relative to a strategy without it, there was not robust enough evidence to recommend a specific place for aripiprazole within the treatment pathway.

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Acknowledgements

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number 09/123/01). See the HTA programme website for further project information (http://www.hta.ac.uk). This summary of the ERG report was compiled after the National Institute for Health Care Excellence (NICE) issued guidance.

LU drafted the final version of the manuscript and takes responsibility as the overall guarantor of the content. BK, SR and MS revised the manuscript for important intellectual content. All authors have given their approval for the final version to be published.

The authors acknowledge the clinical advice provided by Dr Bernadka Dubicka (Consultant Adolescent Psychiatrist), Dr Argyris Stringaris (Consultant Child and Adolescent Psychiatrist) and Dr Isobel Heyman (Consultant Child and Adolescent Psychiatrist). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. The authors also acknowledge Ruth Wong, who contributed to the work but did not meet the criteria for authorship.

Conflicts of Interest

The authors have no potential conflicts of interest that are directly relevant to the content of this article.

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  1. School of Health and Related Research, University of Sheffield, Sheffield, S1 4DA, UK

    Lesley Uttley, Ben Kearns, Shijie Ren & Matt Stevenson

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  1. Lesley Uttley
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Correspondence to Lesley Uttley.

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Uttley, L., Kearns, B., Ren, S. et al. Aripiprazole for the Treatment and Prevention of Acute Manic and Mixed Episodes in Bipolar I Disorder in Children and Adolescents: A NICE Single Technology Appraisal. PharmacoEconomics 31, 981–990 (2013). https://doi.org/10.1007/s40273-013-0091-0

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