PDF herunterladen
Pharmacopsychiatry 2019; 52(01): 24-31
DOI: 10.1055/s-0044-101466
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials

Wei Zheng   *
1   The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
,
Qing-E Zhang   *
2   The National Clinical Research Center for Mental Disorders, China & Center of Depression, Beijing Institute for Brain Disorders & Mood Disorders Center, Beijing Anding Hospital, Capital Medical University, Beijing, China
,
Dong-Bin Cai
3   Clinics of Chinese Medicine, First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
,
Xin-Hu Yang
1   The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
,
Gabor S. Ungvari
4   The University of Notre Dame Australia / Graylands Hospital, Perth, Australia
,
Chee H. Ng
5   Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
,
Ren-Rong Wu
6   Mental Health Institute of the Second Xiangya Hospital & National Technology Institute of Psychiatry & Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, China
,
Yu-Tao Xiang
7   Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 11. Juli 2017
revised 25. November 2017

accepted 16. Januar 2018

Publikationsdatum:
27. Februar 2018 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Introduction Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia.

Methods Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals.

Results Six RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods.

Conclusion Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.

Review registration: CRD42017059198

Key words

metformin - lifestyle - weight gain - schizophrenia - meta-analysis

* These authors contributed equally to this work.


Supporting Information

 

  • References

  • 1 Liu Z, Zheng W, Gao S. et al. Metformin for treatment of clozapine-induced weight gain in adult patients with schizophrenia: A meta-analysis. Shanghai Arch Psychiatry 2015; 27: 331-340
    PubMedGoogle Scholar
  • 2 Zheng W, Li XB, Tang YL. et al. Metformin for weight gain and metabolic abnormalities associated with antipsychotic treatment: Meta-analysis of randomized placebo-controlled trials. J Clin Psychopharmacol. 2015; 35: 499-509
    CrossrefPubMedGoogle Scholar
  • 3 Wu RR, Zhao JP, Jin H. et al. Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial. JAMA 2008; 299: 185-193
    PubMedGoogle Scholar
  • 4 Zheng W, Zheng YJ, Li XB. et al. Efficacy and safety of adjunctive aripiprazole in schizophrenia: Meta-analysis of randomized controlled trials. J Clin Psychopharmacol. 2016; 36: 628-636
    CrossrefPubMedGoogle Scholar
  • 5 Curtis J, Watkins A, Rosenbaum S. et al. Evaluating an individualized lifestyle and life skills intervention to prevent antipsychotic-induced weight gain in first-episode psychosis. Early Interv Psychiatry 2016; 10: 267-276
    CrossrefPubMedGoogle Scholar
  • 6 Maayan L, Vakhrusheva J, Correll CU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: A systematic review and meta-analysis. Neuropsychopharmacology 2010; 35: 1520-1530
    CrossrefPubMedGoogle Scholar
  • 7 Cooper SJ, Reynolds GP, Barnes T. et al. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. J Psychopharmacol. 2016; 30: 717-748
    CrossrefPubMedGoogle Scholar
  • 8 Zheng W, Xiang YQ, Ungvari GS. et al. Amantadine for antipsychotic-related weight gain: Meta-analysis of randomized placebo-controlled trials. J Clin Psychopharmacol. 2017; 37: 341-346
    CrossrefPubMedGoogle Scholar
  • 9 Templeman LA, Reynolds GP, Arranz B. et al. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005; 15: 195-200
    CrossrefPubMedGoogle Scholar
  • 10 Deng C, Weston-Green K, Huang XF. The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain?. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1-4
    CrossrefPubMedGoogle Scholar
  • 11 Yeo S, Walker JS, Caughey MC. et al. What characteristics of nutrition and physical activity interventions are key to effectively reducing weight gain in obese or overweight pregnant women? A systematic review and meta-analysis. Obes Rev. 2017; 18: 385-399
    CrossrefPubMedGoogle Scholar
  • 12 Webb VL, Wadden TA. Intensive lifestyle intervention for obesity: principles, practices, and results. Gastroenterology 2017; 152: 1752-1764
    CrossrefPubMedGoogle Scholar
  • 13 Sun Y, You W, Almeida F. et al. The effectiveness and cost of lifestyle interventions including nutrition education for diabetes prevention: A systematic review and meta-analysis. J Acad Nutr Diet 2017; 117: 404-421
    CrossrefPubMedGoogle Scholar
  • 14 Forsberg KA, Bjorkman T, Sandman PO. et al. Physical health–a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff. Nord J Psychiatry 2008; 62: 486-495
    CrossrefPubMedGoogle Scholar
  • 15 Attux C, Martini LC, Elkis H. et al. A 6-month randomized controlled trial to test the efficacy of a lifestyle intervention for weight gain management in schizophrenia. BMC Psychiatry 2013; 13: 60
    CrossrefPubMedGoogle Scholar
  • 16 Alvarez-Jiménez M, Hetrick SE, González-Blanch C. et al. Non-pharmacological management of antipsychotic-induced weight gain: Systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2008; 193: 101-107
    CrossrefPubMedGoogle Scholar
  • 17 Wu RR, Zhao JP, Guo XF. et al. Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: A double-blind, placebo-controlled study. Am J Psychiatry. 2008; 165: 352-358
    CrossrefPubMedGoogle Scholar
  • 18 Wu RR, Zhang FY, Gao KM. et al. Metformin treatment of antipsychotic-induced dyslipidemia: An analysis of two randomized, placebo-controlled trials. Mol Psychiatry. 2016; 21: 1537-1544
    PubMedGoogle Scholar
  • 19 Klein DJ, Cottingham EM, Sorter M. et al. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry. 2006; 163: 2072-2079
    CrossrefPubMedGoogle Scholar
  • 20 Mizuno Y, Suzuki T, Nakagawa A. et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: A systematic review and meta-analysis. Schizophr Bull. 2014; 40: 1385-1403
    CrossrefPubMedGoogle Scholar
  • 21 de Silva VA, Suraweera C, Ratnatunga SS. et al. Metformin in prevention and treatment of antipsychotic induced weight gain: A systematic review and meta-analysis. BMC Psychiatry 2016; 16: 341
    CrossrefPubMedGoogle Scholar
  • 22 Siskind DJ, Leung J, Russell AW. et al. Metformin for clozapine associated obesity: A systematic review and meta-analysis. PloS One 2016; 11: e0156208
    CrossrefPubMedGoogle Scholar
  • 23 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med. 2009; 151: 264-269
    CrossrefPubMedGoogle Scholar
  • 24 Baptista T, Martínez J, Lacruz A. et al. Metformin for prevention of weight gain and insulin resistance with olanzapine: A double-blind placebo-controlled trial. Can J Psychiatry. 2006; 51: 192-196
    CrossrefPubMedGoogle Scholar
  • 25 Baptista T, Rangel N, Fernández V. et al. Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: A multicentric, double-blind, placebo-controlled trial. Schizophr Res. 2007; 93: 99-108
    CrossrefPubMedGoogle Scholar
  • 26 Jarskog LF, Hamer RM, Catellier DJ. et al. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry. 2013; 170: 1032-1040
    CrossrefPubMedGoogle Scholar
  • 27 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13: 261-276
    CrossrefPubMedGoogle Scholar
  • 28 Overall JE, Gorham DR. The brief psychiatric rating-scale. Psychol Rep. 1962; 10: 799-812
    CrossrefPubMedGoogle Scholar
  • 29 Higgins J, Higgins J. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, UK: John Wiley & Sons; 2008
    Google Scholar
  • 30 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
    CrossrefPubMedGoogle Scholar
  • 31 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21: 1539-1558
    CrossrefPubMedGoogle Scholar
  • 32 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
    CrossrefPubMedGoogle Scholar
  • 33 Jadad AR, Moore RA, Carroll D. et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17: 1-12
    CrossrefPubMedGoogle Scholar
  • 34 Balshem H, Helfand M, Schunemann HJ. et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011; 64: 401-406
    CrossrefPubMedGoogle Scholar
  • 35 Atkins D, Best D, Briss PA. et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490
    CrossrefPubMedGoogle Scholar
  • 36 Chen JX, Wu SY, Lin R. et al. The efficacy of metformin in combination with life style intervention on body weight, blood lipid and blood glucose in schizophrenia during clozapine treatment. Sichuan Mental Health 2010; 23: 198-202
    PubMedGoogle Scholar
  • 37 Du YH, Lv HJ. Effect of metformin combined with behavioral intervention on body weight increasing and glucose and lipid metabolism disorder of schizophrenic patients. Journal of Xinxiang Medical University 2014; 31: 381-384
    PubMedGoogle Scholar
  • 38 Mi ZY, Shi XL. Metformin with behavior intervention in treatment of antipsychotic-induced metabolic disorders. China Pharmaceuticals 2014; 23: 87-89
    PubMedGoogle Scholar
  • 39 Wang XL. Metformin with lifestyle intervention in treatment of clozapine-induced metabolic disorders. Medica of China Family Physicians 2009; 12: 840-842
    PubMedGoogle Scholar
  • 40 Xia JX, Wang YB, Gan JG. et al. Efficacy of metformin combined behavior intervention in the treatment of metabolic disorders caused by risperidone. The Chinese Journal of Clinical Pharmacology 2011; 27: 417-419
    PubMedGoogle Scholar
  • 41 Mukundan A, Faulkner G, Cohn T. et al. Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems. Cochrane Database Syst Rev. 2010; 12: CD006629
    PubMedGoogle Scholar
  • 42 Zheng W, Xiang YT, Xiang YQ. et al. Efficacy and safety of adjunctive topiramate for schizophrenia: A meta-analysis of randomized controlled trials. Acta Psychiatr Scand. 2016; 134: 385-398
    CrossrefPubMedGoogle Scholar
  • 43 Zheng W, Yang XH, Cai DB. et al. Adjunctive metformin for antipsychotic-related hyperprolactinemia: A meta-analysis of randomized controlled trials. J Psychopharmacol. 2017; 31: 625-631
    CrossrefPubMedGoogle Scholar
  • 44 Chittaranjan A. Use of metformin for cardiometabolic risks in psychiatric practice: Need-to-know safety issues. J Clin Psychiatry. 2016; 77: e1491-e1494
    CrossrefPubMedGoogle Scholar
  • 45 Alvarez-Jiménez M, González-Blanch C, Vázquez-Barquero JL. et al. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial. J Clin Psychiatry. 2006; 67: 1253-1260
    CrossrefPubMedGoogle Scholar