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Weight Gain and Other Metabolic Adverse Effects Associated with Atypical Antipsychotic Treatment of Children and Adolescents: A Systematic Review and Meta-analysis

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Abstract

Objectives

The aims of this study were to provide a systematic review and meta-analysis of the effects of atypical antipsychotics in children and adolescents on weight gain (primary objective) and other metabolic parameters (secondary objective).

Methods

A systematic literature review and meta-analysis of double-blind, randomized, controlled trials were conducted. The data sources used were as follows: EMBASE, PubMed, BIOSIS, International Pharmaceutical Abstracts, The Cochrane database (Clinical Trials), Clinical Trials Government Registry, The metaRegister of Controlled Trials, WHO (World Health Organization) Clinical Trials Registry Platform, and PsycINFO®. Hand searching was also carried out by examining the reference lists of identified studies. Double-blind, randomized, controlled trials investigating the metabolic adverse effects (weight gain, lipid, glucose, and prolactin level abnormalities) associated with atypical antipsychotic use in children and adolescents aged ≤18 years were included, irrespective of whether the investigation of adverse effects was a primary or secondary endpoint.

Results

We identified 21 studies of drug versus placebo that met the inclusion criteria, with a total of 2,455 patients, 14 studies for risperidone (1,331 patients), three for olanzapine (276 patients), and four for aripiprazole (848 patients). Compared with placebo, the mean weight increases for each drug were olanzapine 3.45 kg (95 % CI 2.93–3.98), risperidone 1.77 kg (95 % CI 1.35–2.20), and aripiprazole 0.94 kg (95 % CI 0.65–1.24). Regarding other metabolic abnormalities, eight studies reported statistically significant increases in prolactin with risperidone; two reported a statistically significant increase in glucose, total cholesterol, and prolactin with olanzapine; and three studies reported a statistically significant decrease in prolactin with aripiprazole. Data on lipid, glucose, and prolactin level changes were too limited to allow us to perform a meta-analysis.

Conclusions

Olanzapine, risperidone, and aripiprazole were all associated with statistically significant weight gain. Olanzapine was associated with the most weight gain and aripiprazole the least. For the secondary outcome, although a number of active comparator trials were identified, data were not available for meta-analysis and were too limited to allow firm conclusions to be drawn.

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Acknowledgments

I.C.K.W., F.M.C.B., K.J.A., M.L.M., and N.B.A. conceived the idea of the study. All authors were involved in the study design. N.B.A. and Y.L. analyzed the data; N.B.A., F.M.C.B., M.L.M., and I.C.K.W. interpreted the data. All authors had full access to the study data and can take responsibility for the integrity of the data and the accuracy of the data analysis. All authors drafted, revised, and approved the final manuscript. I.C.K.W. and F.M.C.B. supervised the study.

Conflicts of interest and funding

F.M.C.B. has received lecture fees, consultancy fees, research grants, and equipment grants from, and has been sponsored to attend conferences by, various pharmaceutical companies. He was previously editor-in-chief of a journal sponsored by GlaxoSmithKline. He has been asked to organize conferences supported by an unrestricted educational grant from Janssen-Cilag, a company marketing risperidone. None of these monies have been paid directly to F.M.C.B.; all monies since 2001 have been paid to his NHS Trust. F.M.C.B. has recently been sponsored to attend international epilepsy conferences by Eisai. No monies are currently being received from pharmaceutical companies, or from any source other than his employer, the NHS in the UK. K.J.A. has been on the Advisory Board for the Bristol-Myers Squibb and Otsuka Pharmaceuticals Ltd, and in addition, has received consultancy fees including payment for lectures and educational presentations from the same company. She was previously a member of various advisory boards, receiving consultancy fees and honoraria, and has received research grants from various companies, including Lundbeck and GlaxoSmithKline. She currently holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. I.C.K.W. has received research funding and honoraria from various pharmaceutical companies, including Janssen-Cilag and Bristol-Myers Squibb (manufacturers of antipsychotic medicines). I.C.K.W. is currently receiving funding from the EU Commission to investigate the safety of risperidone in children. M.L.M. has received funding from pharmaceutical companies (Shire and Pfizer), but none of the funding is related to this study. The authors N.B.A. and Y.L. declare that they have no conflict of interest. N.B.A. is supported by a scholarship from the Ministry of Higher Education in the Kingdom of Saudi Arabia. No additional sources of funding were used to prepare this manuscript.

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Authors and Affiliations

  1. Centre for Paediatric Pharmacy Research, University College London School of Pharmacy, London, WC1N 1AX, UK

    Noor B. Almandil, Ying Liu, Macey L. Murray, Frank M. C. Besag & Ian C. K. Wong

  2. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, 21 Sassoon Road, 2/F Laboratory Block, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China

    Ying Liu & Ian C. K. Wong

  3. Child and Adolescent Mental Health Service, Children’s Learning Disability Team, SEPT: South Essex Partnership NHS Trust, 24 Grove Place, Bedford, MK40 3JJ, UK

    Frank M. C. Besag

  4. Alberta Centennial Addiction and Mental Health Research Chair, Department of Psychiatry, 5-142 Katz Group Centre, University of Alberta, Edmonton, AB, T6G 2E1, Canada

    Katherine J. Aitchison

  5. Institute of Psychiatry, MRC SGDP Centre, King’s College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK

    Katherine J. Aitchison

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  1. Noor B. Almandil
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Almandil, N.B., Liu, Y., Murray, M.L. et al. Weight Gain and Other Metabolic Adverse Effects Associated with Atypical Antipsychotic Treatment of Children and Adolescents: A Systematic Review and Meta-analysis. Pediatr Drugs 15, 139–150 (2013). https://doi.org/10.1007/s40272-013-0016-6

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