’frontiers
`REVIEW
`published: 28 November 2018
`dor: 10.3389/‘l‘phar201801393
`in Pharmacology
`
`®Mb!
`W
`
`Topiramate and Metformin Are
`Effective Add-On Treatments in
`
`Controlling Antipsychotic-Induced
`Weight Gain: A Systematic Review
`and Network Meta-Analysis
`
`Chuanjun 2114;011:453", Yong Xu‘Mf, Sha Lia‘s-9T, Jing Li‘5v‘, Qishi Zheng 7,
`Xiangyang Gao‘, Shen Li‘, Rixing Jing”, Xueqin Song”, Weihua YueW“,
`Chunhua Zhou’“ and Rachel Upthegrove“-'5
`
`’ Department of Psychiatry and Morbidity, Tiary'in Anding Hospital, Tiary'in Medical Lhimrsity, Tianjin, China, 2 Department
`of Psychiatry, Jining Medical University, Jining, China, a Department of Psychiatry, Tiary‘in Medical University, 77anin, China,
`‘ Department of Psychiatry. First Hospital/First Clinical Medical Cbllege of Shanxi Medical University. Taiyuan, China. 5 MDT
`Center for Cognitive Impa'rment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan, China,
`'5 Department of Neurobiology, National Key Discrplines, Key Laboratory for Oelular Physiology of Ministry of Education,
`Shanxi Medical University, Taiyuan, China, 7 Department of Epidemiology, Singapore Cinical Research Institute, Singapore,
`Singapore, ‘ Health Management Institute, Big Data Analysis Center, Chinese PLA General Hospital. Being. China,
`9 Department of Pattern Recogtition, China National Key Laboratory, Institute 0! Automation, Ch'nese Academy 0! Sciences,
`Being. China,
`’° Department otPsychiatry, First Affiliated Hospital of Ztengzhou University, Ztengzhou. China, " Peking
`University Sixth Hospital, Institute of Mental Health, Bering, China, ’2 Key Laboratory of Mental Health. Ministry of Health 8
`National Clinical Research Center for Mental Disorders, Peking University, Beiihg, China, '3 Department ofPhannacy, Hebei
`Medical University First Hospital, Shiiazhuang, China. " Institute for Marital Health, University of Birmingham, Birmingham,
`United Kingdom, ’5 Ear1y Intervention Service, Fon/vaid 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-one, 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
`
`OPEN ACCESS
`
`Edited by:
`Tahir Mehmood Khan,
`bhiversity of beten‘nary and Animal
`Sciences, Pala'stan
`
`Reviewed by:
`Marc Henri De Longuevrlle,
`(EB Phanna, Belgium
`Kurt Neumann,
`Independent Researcher, Keréktelela',
`Htmgary
`
`‘COrrespondence:
`Chunhua Zhou
`zhouchunhua80© 126. com
`Chuary‘un Zhuo
`chuanpnzhuotjmh©1£iicom;
`chuary’unzhuotjmlflieeeorg
`Wehua Yue
`diyue@bjmu:edu.cn
`’These authors have contributed
`equally to this work
`
`Specialty seofion:
`This article was submitted to
`Pharmaceutical Medicine
`and Outcomes Research,
`a section of the joumal
`Frontiers in Pharmacology
`
`Received: 19 September 2018
`Accepted: 12 November 2018
`Published: 28 November 2018
`
`Citation:
`ZruoC, XuY, LiuS, UJ,
`Zteng Q, GaoX. Li S, Jing R, Song X,
`We W, Zhou C and Upthegrove R
`(2018) Topiramate and Methrmin Are
`Effective Add—On Treatments
`in Controling Antipsychotic-Induced
`Weight Gain: A Qstematic Review
`and Network Meta—Analysis.
`Front. Pharmacol. 9: 1393.
`doi: 10.3389/Iphan2018.01393
`
`
`
`Frontiers in Pharmaookjgy | wwwfrontlersmtorg
`
`1
`
`November 2018 | Volume 9| Article 1393
`Exhibit 2098
`Slaybadt v. Sumitomo
`IPR2020—01053
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`Zhuo et al. Add—Ons for Controlling Antipsychotic—lnduced Weight Gain
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`(n = 480)
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`(n = 119)
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`(n = 614)
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`through other sources
`(n = 0)
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`(n = 599)
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`in = 599)
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`(n =92)
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`Studies included in full-review
`
`(n = 27)
`No. of studies on Metformin: 13
`
`No. of studies on Ranitidine: 2
`
`No. of studies on Topiramate: 4
`No. of studies on Sibutramine: 4
`
`No. of studies on Reboxetine: 3
`
`
`
`
`FIGURE 1 | PRISMA flowchart of study selection.
`
`Frontiers in Pharmacology | www.lrontiersin.org
`
`4
`
`November 2018 | Volume 9 | Article 1393
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