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Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis.
CNS Drugs. 2018 12; 32(12):1103-1112.CD

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.

Authors+Show Affiliations

Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, 48 Boulevard Sérurier, 75019, Paris, France. pierre.ellul1987@gmail.com.Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, 48 Boulevard Sérurier, 75019, Paris, France. Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.Center for Innovation in Mental Health, Academic Unit of Psychology, University of Southampton, Southampton, UK. Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK. Solent NHS Trust, Southampton, UK. New York University Child Study Center, New York, NY, USA. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

30238318

Citation

Ellul, Pierre, et al. "Metformin for Weight Gain Associated With Second-Generation Antipsychotics in Children and Adolescents: a Systematic Review and Meta-Analysis." CNS Drugs, vol. 32, no. 12, 2018, pp. 1103-1112.
Ellul P, Delorme R, Cortese S. Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis. CNS Drugs. 2018;32(12):1103-1112.
Ellul, P., Delorme, R., & Cortese, S. (2018). Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis. CNS Drugs, 32(12), 1103-1112. https://doi.org/10.1007/s40263-018-0571-z
Ellul P, Delorme R, Cortese S. Metformin for Weight Gain Associated With Second-Generation Antipsychotics in Children and Adolescents: a Systematic Review and Meta-Analysis. CNS Drugs. 2018;32(12):1103-1112. PubMed PMID: 30238318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis. AU - Ellul,Pierre, AU - Delorme,Richard, AU - Cortese,Samuele, PY - 2018/9/22/pubmed PY - 2019/10/15/medline PY - 2018/9/22/entrez SP - 1103 EP - 1112 JF - CNS drugs JO - CNS Drugs VL - 32 IS - 12 N2 - 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. SN - 1179-1934 UR - https://www.unboundmedicine.com/medline/citation/30238318/Metformin_for_Weight_Gain_Associated_with_Second_Generation_Antipsychotics_in_Children_and_Adolescents:_A_Systematic_Review_and_Meta_Analysis_ L2 - https://dx.doi.org/10.1007/s40263-018-0571-z DB - PRIME DP - Unbound Medicine ER -