Systematic Review

Pediatric Drugs

, Volume 15, Issue 2, pp 139-150

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

  • Noor B. AlmandilAffiliated withCentre for Paediatric Pharmacy Research, University College London School of Pharmacy
  • , Ying LiuAffiliated withCentre for Paediatric Pharmacy Research, University College London School of PharmacyCentre 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
  • , Macey L. MurrayAffiliated withCentre for Paediatric Pharmacy Research, University College London School of Pharmacy
  • , Frank M. C. BesagAffiliated withCentre for Paediatric Pharmacy Research, University College London School of PharmacyChild and Adolescent Mental Health Service, Children’s Learning Disability Team, SEPT: South Essex Partnership NHS Trust
  • , Katherine J. AitchisonAffiliated withAlberta Centennial Addiction and Mental Health Research Chair, Department of Psychiatry, 5-142 Katz Group Centre, University of AlbertaInstitute of Psychiatry, MRC SGDP Centre, King’s College London
  • , Ian C. K. WongAffiliated withCentre for Paediatric Pharmacy Research, University College London School of PharmacyCentre 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 Email author 

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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.