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Front Pharmacol. 2018 Nov 28;9:1393. doi: 10.3389/fphar.2018.01393. eCollection 2018.

Topiramate and Metformin Are Effective Add-On Treatments in Controlling Antipsychotic-Induced Weight Gain: A Systematic Review and Network Meta-Analysis.

Zhuo C1,2,3,4,5,6, Xu Y4,5,6, Liu S4,5,6, Li J4,5,6, Zheng Q7, Gao X8, Li S3, Jing R9, Song X10, Yue W11,12, Zhou C13, Upthegrove R14,15.

Author information

Department of Psychiatry and Morbidity, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China.
Department of Psychiatry, Jining Medical University, Jining, China.
Department of Psychiatry, Tianjin Medical University, Tianjin, China.
Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
MDT Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan, China.
Department of Neurobiology, National Key Disciplines, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
Department of Epidemiology, Singapore Clinical Research Institute, Singapore, Singapore.
Health Management Institute, Big Data Analysis Center, Chinese PLA General Hospital, Beijing, China.
Department of Pattern Recognition, China National Key Laboratory, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Department of Psychiatry, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Peking University Sixth Hospital, Institute of Mental Health, Beijing, China.
Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China.
Department of Pharmacy, Hebei Medical University First Hospital, Shijiazhuang, China.
Institute for Mental Health, University of Birmingham, Birmingham, United Kingdom.
Early Intervention Service, Forward Thinking Birmingham, Birmingham, United Kingdom.


Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes, dyslipidemia, and cardiovascular disease. The current systematic review and network meta-analysis analyzes and provides an update on the clinical performance of these add-ons in comparison to placebo on body weight and body mass index (BMI) reductions. Methods: A comprehensive literature search was performed on electronic databases: PubMed (1946-), Embase (1974-), Cochrane library (1992-), and OpenGrey (2000-) until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI change and withdrawn due to adverse events of different pharmacological add-ons, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. To rank the prognosis for all add-ons, we used surface under the cumulative ranking (SUCRA) values. Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects) were included. All the studies demonstrated low to moderate risk of bias. For the analysis of body weight change, all add-ons except Ranitidine showed significant weight reductions comparing to placebo. The effectiveness rank based on SUCRA results from highest to lowest was Sibutramine, Topiramate, Metformin, Reboxetine, Ranitidine, and placebo. A similar pattern was seen for BMI change. The analysis of safety outcome did not detect significantly increased withdrawn number from the add-ons. Current evidence showed relatively good tolerance and safety of using the pharmacological add-ons. Interpretation: Topiramate and Metformin are effective add-on treatments in controlling antipsychotic-induced weight gain, comparing to placebo. They are well tolerated in short-term period. Although Sibutramine has the highest rank of the effectiveness, its license has been withdrawn in many countries due to its adverse effects. Hence, Sibutramine should not be adopted to treat antipsychotic-induced weight gain.


antipsychotic-induced weight gain; metformin; network meta-analysis; pharmacological add-ons; topiramate

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