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CNS Drugs
Published in: CNS Drugs 12/2018

01-12-2018 | Systematic Review

Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis

Authors: Pierre Ellul, Richard Delorme, Samuele Cortese

Published in: CNS Drugs | Issue 12/2018

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Abstract

Background

Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs.

Objective

The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs.

Methods

Based on a pre-registered protocol (PROSPERO–CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18 years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool.

Results

Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16 weeks of treatment {mean difference − 0.98 kg (95% confidence interval [CI] − 1.26, − 0.69); − 1.83 kg (95% CI − 2.47, − 1.18); and − 3.23 kg (95% CI − 5.59, − 0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias.

Conclusion

Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.
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Metadata
Title
Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis
Authors
Pierre Ellul
Richard Delorme
Samuele Cortese
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 12/2018
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-018-0571-z

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