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Current Psychiatry Reports
Published in: Current Psychiatry Reports 11/2023

27-09-2023 | Antipsychotics

Antipsychotic-Induced Weight Gain in Severe Mental Illness: Risk Factors and Special Considerations

Authors: Nicolette Stogios, Bailey Humber, Sri Mahavir Agarwal, Margaret Hahn

Published in: Current Psychiatry Reports | Issue 11/2023

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Abstract

Purpose of Review

Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and risk factors for antipsychotic-induced weight gain (AIWG), and evidence for interventions, including special considerations.

Recent Findings

Predisposing risk factors for AIWG include lack of prior AP exposure, sex, and age. AP dose and duration of exposure are additional treatment-related factors that may contribute to this issue. Among current approaches to target AIWG, metformin has the most evidence to support its use, and this is increasingly reflected in clinical guidelines. While lifestyle approaches are recommended, cost-effectiveness and scalability represent limitations.

Summary

More research is needed to identify newer treatment options and inform clinical recommendations for AIWG. Concerns around scope of practice in psychiatry to address AIWG and related comorbidities will require enhanced training opportunities and interdisciplinary collaborations, as well as updated position statements/practice guidelines emphasizing prevention.
Literature
1.
Westman J, Eriksson SV, Gissler M, Hällgren J, Prieto ML, Bobo WV, et al. Increased cardiovascular mortality in people with schizophrenia: a 24-year national register study. Epidemiol Psychiatr Sci. 2018;27(5):519–27.PubMedCrossRef
2.
Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14(3):339–47.PubMedPubMedCentralCrossRef
3.
Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Borglum AD, et al. Endogenous and antipsychotic-related risks for diabetes mellitus in young people with schizophrenia: a Danish population-based cohort study. Am J Psychiatry. 2017;174(7):686–94.PubMedCrossRef
4.
Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005;150(6):1115–21.PubMedCrossRef
5.
Laursen TM, Munk-Olsen T, Vestergaard M. Life expectancy and cardiovascular mortality in persons with schizophrenia. Curr Opin Psychiatry. 2012;25(2):83–8.PubMedCrossRef
6.
Correll CU, Solmi M, Veronese N, Bortolato B, Rosson S, Santonastaso P, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry. 2017;16(2):163–80.PubMedPubMedCentralCrossRef
7.
Nasrallah HA, Meyer JM, Goff DC, McEvoy JP, Davis SM, Stroup TS, et al. Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: data from the CATIE schizophrenia trial sample at baseline. Schizophr Res. 2006;86(1–3):15–22.PubMedCrossRef
8.
Amini M, Zayeri F, Salehi M. Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: results from global burden of disease study 2017. BMC Public Health. 2021;21(1):401.PubMedPubMedCentralCrossRef
9.
Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, “just the facts” 5. Treatment and prevention. Past, present, and future. Schizophr Res. 2010;122(1–3):1–23.PubMedCrossRef
10.
Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063–71.PubMedCrossRef
11.
Pringsheim T, Gardner DM. Dispensed prescriptions for quetiapine and other second-generation antipsychotics in Canada from 2005 to 2012: a descriptive study. CMAJ Open. 2014;2(4):E225–32.PubMedPubMedCentralCrossRef
12.
Radojčić MR, Pierce M, Hope H, Senior M, Taxiarchi VP, Trefan L, et al. Trends in antipsychotic prescribing to children and adolescents in England: cohort study using 2000–19 primary care data. Lancet Psychiatry. 2023;10(2):119–28.PubMedCrossRef
13.
Pringsheim T, Gorman D, Pringsheim T, Gorman D. Second-generation antipsychotics for the treatment of disruptive behaviour disorders in children: a systematic review. Can J Psychiat. 2012;57(12):722–7.CrossRef
14.
Pringsheim T, Lam D, Patten SB. The pharmacoepidemiology of antipsychotic medications for Canadian children and adolescents: 2005–2009. J Child Adolesc Psychopharmacol. 2011;21(6):537–43.PubMedCrossRef
15.
Correll CU, Detraux J, De Lepeleire J, De Hert M. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry. 2015;14(2):119–36.PubMedPubMedCentralCrossRef
16.
Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015;14(1):73–96.PubMedCrossRef
17.
Kowalchuk C, Castellani LN, Chintoh A, Remington G, Giacca A, Hahn MK. Antipsychotics and glucose metabolism: how brain and body collide. Am J Physiol Endocrinol Metab. 2019;316(1):E1–15.PubMedCrossRef
18.
Werner FM, Coveñas R. Safety of antipsychotic drugs: focus on therapeutic and adverse effects. Expert Opin Drug Saf. 2014;13(8):1031–42.PubMedCrossRef
19.
Vrbová K, Kamarádová D, Látalová K, Ocisková M, Praško J, Mainerová B, et al. Self-stigma and adherence to medication in patients with psychotic disorders–cross-sectional study. Neuro Endocrinol Lett. 2014;35(7):645–52.PubMed
20.
Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017;47(6):1030–40.PubMedCrossRef
21.
Cooper SJ, Reynolds GP, Barnes T, England E, Haddad P, Heald A, 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(8):717–48.PubMedCrossRef
22.
Simon J, Wienand D, Park AL, Wippel C, Mayer S, Heilig D, et al. Excess resource use and costs of physical comorbidities in individuals with mental health disorders: a systematic literature review and meta-analysis. Eur Neuropsychopharmacol. 2023;66:14–27.PubMedCrossRef
23.
Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686–96.PubMedCrossRef
24.
• Barton BB, Segger F, Fischer K, Obermeier M, Musil R. Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf. 2020;19(3):295–314. A large meta-analysis demonstrating that all antipsychotics, including first-generation agents, induce significant weight gain; most also cause clinically significant weight gain ≥7%.PubMedCrossRef
25.
26.
Tarricone I, Ferrari Gozzi B, Serretti A, Grieco D, Berardi D. Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychol Med. 2010;40(2):187–200.PubMedCrossRef
27.
•• Campforts B, Drukker M, Crins J, Van Amelsvoort T, Bak M. Association between antipsychotic medication and clinically relevant weight change: meta-analysis. BJPsych Open. 2023;9(1). This study conducted large meta-analyses and meta-regressions to better understand risk factors and moderators of clinically significant AIWG. AIWG was more pronounced in first-episode patients, individuals with schizophrenia, and longer duration of AP use.
28.
Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008;371(9618):1085–97.PubMedCrossRef
29.
Chang S-C, Goh KK, Lu M-L. Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: state-of-the-art and future perspectives. World J Psychiatry. 2021;11(10):696–710.PubMedPubMedCentralCrossRef
30.
Benarroch L, Kowalchuk C, Wilson V, Teo C, Guenette M, Chintoh A, et al. Atypical antipsychotics and effects on feeding: from mice to men. Psychopharmacology. 2016;233(14):2629–53.PubMedCrossRef
31.
Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017;13:2231–41.PubMedPubMedCentralCrossRef
32.
Roerig JL, Steffen KJ, Mitchell JE. Atypical antipsychotic-induced weight gain. CNS Drugs. 2011;25(12):1035–59.PubMedCrossRef
33.
Carlsson A. Antipsychotic drugs, neurotransmitters, and schizophrenia. Am J Psychiatry. 1978;135(2):165–73.PubMedCrossRef
34.
Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003;160(1):13–23.PubMedCrossRef
35.
Nicol GE, Kolko R, Lenze EJ, Yingling MD, Miller JP, Ricchio AR, et al. Adiposity, hepatic triglyceride, and carotid intima media thickness during behavioral weight loss treatment in antipsychotic-treated youth: a randomized pilot study. J Child Adolesc Psychopharmacol. 2019;29(6):439–47.PubMedPubMedCentralCrossRef
36.
Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623–8.PubMedPubMedCentralCrossRef
37.
Singh R, Stogios N, Smith E, Lee J, Maksyutynsk K, Au E, et al. Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review. Ther Adv Psychopharmacol. 2022;12:204512532210965.CrossRef
38.
Singh R, Bansal Y, Medhi B, Kuhad A. Antipsychotics-induced metabolic alterations: Recounting the mechanistic insights, therapeutic targets and pharmacological alternatives. Eur J Pharmacol. 2019;844:231–40.PubMedCrossRef
39.
40.
Fonseka TM, Müller DJ, Kennedy SH. Inflammatory cytokines and antipsychotic-induced weight gain: review and clinical implications. Mol Neuropsychiatry. 2016;2(1):1–14.PubMedPubMedCentral
41.
Jin H, Meyer JM, Mudaliar S, Jeste DV. Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin. Schizophr Res. 2008;100(1):70–85.PubMedPubMedCentralCrossRef
42.
Stubbs B, Wang AK, Vancampfort D, Miller BJ. Are leptin levels increased among people with schizophrenia versus controls? A systematic review and comparative meta-analysis. Psychoneuroendocrinology. 2016;63:144–54.PubMedCrossRef
43.
Ragguett RM, Hahn M, Messina G, Chieffi S, Monda M, De Luca V. Association between antipsychotic treatment and leptin levels across multiple psychiatric populations: an updated meta-analysis. Hum Psychopharmacol. 2017;32(6).
44.
Bartoli F, Lax A, Crocamo C, Clerici M, Carrà G. Plasma adiponectin levels in schizophrenia and role of second-generation antipsychotics: a meta-analysis. Psychoneuroendocrinology. 2015;56:179–89.PubMedCrossRef
45.
Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R, et al. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. Neuropsychopharmacology. 2008;33(7):1633–41.PubMedCrossRef
46.
Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen H-L, Rickels K. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes. 2013;62(9):3232–40.PubMedPubMedCentralCrossRef
47.
Agarwal SM, Caravaggio F, Costa-Dookhan KA, Castellani L, Kowalchuk C, Asgariroozbehani R, et al. Brain insulin action in schizophrenia: something borrowed and something new. Neuropharmacology. 2020;163:107633.PubMedCrossRef
48.
Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, et al. Brain dopamine and obesity. Lancet. 2001;357(9253):354–7.PubMedCrossRef
49.
Stogios N, Smith E, Asgariroozbehani R, Hamel L, Gdanski A, Selby P, et al. Exploring patterns of disturbed eating in psychosis: a scoping review. Nutrients. 2020;12(12).
50.
Shams TA, Müller DJ. Antipsychotic induced weight gain: genetics, epigenetics, and biomarkers reviewed. Curr Psychiatry Rep. 2014;16(10).
51.
Ye W, Xing J, Yu Z, Hu X, Zhao Y. Mechanism and treatments of antipsychotic-induced weight gain. Int J Obesity. 2023.
52.
Castellani LN, Costa-Dookhan KA, McIntyre WB, Wright DC, Flowers SA, Hahn MK, et al. Preclinical and clinical sex differences in antipsychotic-induced metabolic disturbances: a narrative review of adiposity and glucose metabolism. J Psychiatr Brain Sci. 2019;4.
53.
Lee S-Y, Park M-H, Patkar AA, Pae C-U. A retrospective comparison of BMI changes and the potential risk factors among schizophrenic inpatients treated with aripiprazole, olanzapine, quetiapine or risperidone. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):490–6.PubMedCrossRef
54.
Lau SL, Muir C, Assur Y, Beach R, Tran B, Bartrop R, et al. Predicting weight gain in patients treated with clozapine: the role of sex, body mass index, and smoking. J Clin Psychopharmacol. 2016;36(2):120–4.PubMedCrossRef
55.
Gebhardt S, Haberhausen M, Heinzel-Gutenbrunner M, Gebhardt N, Remschmidt H, Krieg JC, et al. Antipsychotic-induced body weight gain: predictors and a systematic categorization of the long-term weight course. J Psychiatr Res. 2009;43(6):620–6.PubMedCrossRef
56.
Konarzewska B, Stefańska E, Wendołowicz A, Cwalina U, Golonko A, Małus A, et al. Visceral obesity in normal-weight patients suffering from chronic schizophrenia. BMC Psychiatry. 2014;14(1):35.PubMedPubMedCentralCrossRef
57.
Sugawara N, Yasui-Furukori N, Tsuchimine S, Fujii A, Sato Y, Saito M, et al. Body composition in patients with schizophrenia: comparison with healthy controls. Ann Gen Psychiatry. 2012;11(1):11.PubMedPubMedCentralCrossRef
58.
Zhang ZJ, Yao ZJ, Liu W, Fang Q, Reynolds GP. Effects of antipsychotics on fat deposition and changes in leptin and insulin levels: magnetic resonance imaging study of previously untreated people with schizophrenia. Br J Psychiatry. 2004;184(JAN.):58–62.PubMedCrossRef
59.
Grajales D, Ferreira V, Valverde ÁM. Second-generation antipsychotics and dysregulation of glucose metabolism: beyond weight gain. Cells. 2019;8(11):1336.PubMedPubMedCentralCrossRef
60.
•• Stogios N, Smith E, Bowden S, Tran V, Asgariroozbehani R, McIntyre WB, et al. Metabolic adverse effects of off-label use of second-generation antipsychotics in the adult population: a systematic review and meta-analysis. Neuropsychopharmacology. 2022;47(3):664–72. Systematic review and meta-analysis demonstrating that APs induce significant weight gain in individuals treated with APs for off-label indications (i.e. non-psychotic spectrum disorders).PubMedCrossRef
61.
• Smith E, Stogios N, Au E, Maksyutynska K, De R, Ji A, et al. The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: a systematic review and meta-analysis. Acta Psychiatr Scand. 2022;146(3):201–14. APs induce signficiant weight gain in individuals with intellectual and/or developmental disabilities, an already vulnerable population with intrinsic risk of metabolic dysregulation.PubMedCrossRef
62.
Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302(16):1765–73.PubMedPubMedCentralCrossRef
63.
• Bak M, Drukker M, Cortenraad S, Vandenberk E, Guloksuz S. Antipsychotics result in more weight gain in antipsychotic naive patients than in patients after antipsychotic switch and weight gain is irrespective of psychiatric diagnosis: a meta-analysis. PLoS ONE. 2021;16:e0244944. Meta-analysis of 404 studies, 58 of which were in AP naive patients. All APs resulted in body weight gain in the AP-naïve group; most APs resulted in body weight gain, with exception of amisulpride, aripiprazole, and ziprasidone that showed no body weight gain or even some weight loss after switching APs.PubMedPubMedCentralCrossRef
64.
Marteene W, Hollingworth S, Winckel K, Kisely S, Gallagher E, Siskind D, et al. Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia. Expert Opin Drug Saf. 2019;18(12):1149–60.PubMedCrossRef
65.
Foley DL, Morley KI. Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry. 2011;68(6):609–16.PubMedCrossRef
66.
• Van Der Esch CCL, Kloosterboer SM, Van Der Ende J, Reichart CG, Kouijzer MEJ, De Kroon MMJ, et al. Risk factors and pattern of weight gain in youths using antipsychotic drugs. Eur Child Adolesc Psychiatry. 2021;30(8):1263–71. AIWG is most pronounced during the first 15 weeks of use in youth and adolescents treated with APs.PubMedCrossRef
67.
Libowitz MR, Nurmi EL. The burden of antipsychotic-induced weight gain and metabolic syndrome in children. Front Psych. 2021;12(101545006):623681.CrossRef
68.
• Schoemakers RJ, van Kesteren C, van Rosmalen J, Eussen MLJM, Dieleman HG, Beex-Oosterhuis MM. No differences in weight gain between risperidone and aripiprazole in children and adolescents after 12 months. J Child Adolesc Psychopharmacol. 2019;29(3):192–6. Aripiprazole does not appear to be metabolically neutral in youth and adolescents and shows no difference in terms of weight gain in comparison to risperidone.PubMedCrossRef
69.
Pozzi M, Pisano S, Marano G, Carnovale C, Bravaccio C, Rafaniello C, et al. Weight-change trajectories of pediatric outpatients treated with risperidone or aripiprazole in a naturalistic setting. J Child Adolesc Psychopharmacol. 2018;29(2):133–40.PubMedCrossRef
70.
Guber KM, Cortes ND, Duan L. Risk of obesity among children prescribed atypical antipsychotics for six months or more. J Child Adolesc Psychopharmacol. 2021;32(1):52–60.PubMedCrossRef
71.
Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010;123(2–3):225–33.PubMedPubMedCentralCrossRef
72.
Vandenberghe F, Gholam-Rezaee M, Saigí-Morgui N, Delacrétaz A, Choong E, Solida-Tozzi A, et al. Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment. J Clin Psychiatry. 2015;76(11):e1417–23.PubMedCrossRef
73.
•• Burschinski A, Schneider-Thoma J, Chiocchia V, Schestag K, Wang D, Siafis S, et al. Metabolic side effects in persons with schizophrenia during mid- to long-term treatment with antipsychotics: a network meta-analysis of randomized controlled trials. World Psychiatry. 2023;22(1):116–28. Large network meta-analysis of 137 eligible trials (with 35,007 participants) on 31 antipsychotics that demonstrates the differing propensity of antipsychotic drugs to induce metabolic side effects in mid- to long-term treatment. Given that schizophrenia is often a chronic disorder, these findings should be given more consideration than short-term data in drug choice.PubMedPubMedCentralCrossRef
74.
•• Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64–77. Large network meta-analysis of 100 trials and 25,952 patients that demonstrated olanzapine and clozapine have the worst metabolic profiles while aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone have the most benign profiles.PubMedPubMedCentralCrossRef
75.
• Wu H, Siafis S, Hamza T, Schneider-Thoma J, Davis JM, Salanti G, et al. Antipsychotic-induced weight gain: dose-response meta-analysis of randomized controlled trials. Schizophr Bull. 2022;48(3):643–54. Large-scale meta-analysis demonstrating different dose-response curves of APs in terms of weight gain; this information is important for dosing decisions in clinical practice.PubMedPubMedCentralCrossRef
76.
Piras M, Chahma J, Ranjbar S, Laaboub N, Grosu C, Plessen KJ, et al. Is clozapine-induced weight gain dose-dependent? Results from a prospective cohort study. Schizophr Bull. 2023:sbad009.
77.
American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596–601. https://​doi.​org/​10.​2337/​diacare.​27.​2.​596. PMID: 14747245.
78.
Wharton S, Lau DCW, Vallis M, Sharma AM, Biertho L, Campbell-Scherer D, et al. Obesity in adults: a clinical practice guideline. Can Med Assoc J. 2020;192(31):E875–91.CrossRef
79.
De Hert M, Dekker JM, Wood D, Kahl KG, Holt RIG, Möller HJ. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur Psychiatry. 2009;24(6):412–24.PubMedCrossRef
80.
• Vancampfort D, Firth J, Correll CU, Solmi M, Siskind D, De Hert M, et al. The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials. Focus. 2021;19(1):116–28. Systematic review and meta-analysis of pharmacological and non-pharmacological interventions for treating AIWG; the current evidence for these interventions is still limited and larger trials are urgently needed.PubMedPubMedCentralCrossRef
81.
• Holt RIG, Gossage-Worrall R, Hind D, Bradburn MJ, McCrone P, Morris T, et al. Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial. Br J Psychiatry. 2019;214(2):63–73. STEPWISE is the largest randomized controlled trial to date of a theory-based, group-structured lifestyle education programme in patients with schizophrenia spectrum disorder. The STEPWISE intervention was neither clinically nor cost-effective, emphasizing the need for further research to determine how to manage overweight and obesity in people with schizophrenia.PubMedPubMedCentralCrossRef
82.
•• Speyer H, Jakobsen AS, Westergaard C, Nørgaard HCB, Jørgensen KB, Pisinger C, et al. Lifestyle interventions for weight management in people with serious mental illness: a systematic review with meta-analysis, trial sequential analysis, and meta-regression analysis exploring the mediators and moderators of treatment effects. Psychother Psychosom. 2019;88(6):350–62. Meta-analysis of 41 trials showing that individualized lifestyle treatments have a statistically significant, but not clinically significant mean effect for weight reduction in people with severe mental illness.PubMedCrossRef
83.
Firth J, Cotter J, Elliott R, French P, Yung AR. A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol Med. 2015;45(7):1343–61.PubMedCrossRef
84.
Speyer H, Christian Brix Nørgaard H, Birk M, Karlsen M, Storch Jakobsen A, Pedersen K, et al. The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity. World Psychiatry. 2016;15(2):155–65.PubMedPubMedCentralCrossRef
85.
Firth J, Rosenbaum S, Stubbs B, Gorczynski P, Yung AR, Vancampfort D. Motivating factors and barriers towards exercise in severe mental illness: a systematic review and meta-analysis. Psychol Med. 2016;46(14):2869–81.PubMedPubMedCentralCrossRef
86.
Detke HC, DelBello MP, Landry J, Hoffmann VP, Heinloth A, Dittmann RW. A 52-week study of olanzapine with a randomized behavioral weight counseling intervention in adolescents with schizophrenia or bipolar I disorder. J Child Adolesc Psychopharmacol. 2016;26(10):922–34.PubMedCrossRef
87.
Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW, 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(6):1385–403.PubMedPubMedCentralCrossRef
88.
Agarwal SM, Stogios N, Ahsan Z, Lockwood J, Duncan M, Takeuchi H, et al. S90. A systematic review and meta-analysis of pharmacological interventions for reduction of weight gain in people with schizophrenia: 2019 update. Schizophr Bull. 2020;46(Suppl 1):S68–S68.PubMedCentralCrossRef
89.
Lyu X, Du J, Zhan G, Wu Y, Su H, Zhu Y, et al. Naltrexone and bupropion combination treatment for smoking cessation and weight loss in patients with schizophrenia. Front Pharmacol. 2018;9:181.PubMedPubMedCentralCrossRef
90.
Joffe G, Takala P, Tchoukhine E, Hakko H, Raidma M, Putkonen H, et al. Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity: a 16-week randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008;69(5):706–11.PubMedCrossRef
91.
Taveira TH, Wu WC, Tschibelu E, Borsook D, Simonson DC, Yamamoto R, et al. The effect of naltrexone on body fat mass in olanzapine-treated schizophrenic or schizoaffective patients: a randomized double-blind placebo-controlled pilot study. J Psychopharmacol. 2014;28(4):395–400.PubMedCrossRef
92.
Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020;8(12):960–70.PubMedCrossRef
93.
Lee K, Abraham S, Cleaver R. A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis. Gen Hosp Psychiatry. 2022;78:58–67.PubMedCrossRef
94.
95.
Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397(10278):971–84.PubMedCrossRef
96.
Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083–91.PubMedPubMedCentralCrossRef
97.
Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414–25.PubMedCrossRef
98.
Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325(14):1403–13.PubMedCrossRef
99.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002.PubMedCrossRef
100.
Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022;70(1):5–13.PubMedCrossRef
101.
102.
de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16(1):341.PubMedPubMedCentralCrossRef
103.
• Siskind D, Hahn M, Correll CU, Fink-Jensen A, Russell AW, Bak N, et al. Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: a systematic review and individual participant data meta-analysis. Diabetes Obes Metab. 2019;21(2):293–302. Meta-analysis synthesizing the available evidence for the use of GLP-1RAs for the treatment of AIWG; GLP-1RAs appear to be effective and tolerable for this use, particularly clozapine/olanzapine-treated patients.PubMedCrossRef
104.
Nordisk N. Rybelsus (semaglutide) tablets [prescribing information]. Plainsboro, NJ, Novo Nordisk. 2019.
105.
Siskind D, Russell AW, Gamble C, Winckel K, Mayfield K, Hollingworth S, et al. Treatment of clozapine‐associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: a randomised controlled trial. Diabetes Obes Metab. 2017.
106.
Sass MR, Danielsen AA, Köhler-Forsberg O, Storgaard H, Knop FK, Nielsen M, et al. Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry). BMJ Open. 2023;13(1):e068652.PubMedPubMedCentralCrossRef
107.
Prasad F, De R, Korann V, Chintoh AF, Remington G, Ebdrup BH, et al. Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series. Ther Adv Psychopharmacol. 2023;13:20451253231165170.PubMedPubMedCentralCrossRef
108.
Hahn MK, Cohn T, Teo C, Remington G. Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters. Clin Schizophr Relat Psychoses. 2013;6(4):186–96.PubMedCrossRef
109.
Idrees Z, Cancarevic I, Huang L. FDA-approved pharmacotherapy for weight loss over the last decade. Cureus. 2022;14(9):e29262–362.PubMedPubMedCentral
110.
• Goh KK, Chen CH, Lu ML. Topiramate mitigates weight gain in antipsychotic-treated patients with schizophrenia: meta-analysis of randomised controlled trials. Int J Psychiatry Clin Pract. 2019;23(1):14–32. Meta-analysis of 10 trials showing that topiramate is superior to the control group in mitigating weight gain in antipsychotic-treated patients with schizophrenia.PubMedCrossRef
111.
Zheng W, Xiang YT, Xiang YQ, Li XB, Ungvari G, Chiu H, et al. Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials. Acta Psychiatr Scand. 2016;134(5):385–98.PubMedCrossRef
112.
Agarwal SM, Stogios N. Cardiovascular health in severe mental illness. J Clin Psychiatry. 2022;83(2).
113.
Agarwal SM, Panda R, Costa-Dookhan KA, Mackenzie NE, Treen QC, Caravaggio F, et al. Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial. Transl Psychiatry. 2021;11(1).
114.
Ying MA, Maruschak N, Mansur R, Carvalho AF, Cha DS, McIntyre RS. Metformin: repurposing opportunities for cognitive and mood dysfunction. CNS Neurol Disord Drug Targets. 2014;13(10):1836–45.PubMedCrossRef
115.
Chen Q, Cao T, Li N, Zeng C, Zhang S, Wu X, et al. Repurposing of anti-diabetic agents as a new opportunity to alleviate cognitive impairment in neurodegenerative and neuropsychiatric disorders. Front Pharmacol. 2021;12.
116.
World Health Organisation. Guidelines for the management of physical health conditions in adults with severe mental disorders. World Health Organization. 2018(Licence: CC BY-NC-SA 3.0 IGO).
117.
•• Siskind D, Gallagher E, Winckel K, Hollingworth S, Kisely S, Firth J, et al. Does switching antipsychotics ameliorate weight gain in patients with severe mental illness? A systematic review and meta-analysis. Schizophr Bull. 2021;47(4):948–58. Meta-analysis of 59 studies demonstrating that switching APs to agents with lower weight gain potential can improve weight profiles and other cardiometabolic outcomes; however, the risk of psychiatric relapse in stabe patients must be considered.PubMedPubMedCentralCrossRef
118.
Correll CU, Sikich L, Reeves G, Johnson J, Keeton C, Spanos M, et al. Metformin add-on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial. World Psychiatry. 2020;19(1):69–80.PubMedPubMedCentralCrossRef
119.
120.
Flanagan RJ, Lally J, Gee S, Lyon R, Every-Palmer S. Clozapine in the treatment of refractory schizophrenia: a practical guide for healthcare professionals. Br Med Bull. 2020;135(1):73–89.PubMedPubMedCentralCrossRef
121.
Speyer H, Westergaard C, Albert N, Karlsen M, Stürup AE, Nordentoft M, et al. Reversibility of antipsychotic-induced weight gain: a systematic review and meta-analysis. Front Endocrinol. 2021;12.
122.
Caroff SN, Mu F, Ayyagari R, Schilling T, Abler V, Carroll B. Hospital utilization rates following antipsychotic dose reductions: implications for tardive dyskinesia. BMC Psychiatry. 2018;18(1):306.PubMedPubMedCentralCrossRef
123.
Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and risks of bariatric surgery in adults: a review. JAMA. 2020;324(9):879–87.PubMedCrossRef
124.
125.
• Kouidrat Y, Amad A, Stubbs B, Moore S, Gaughran F. Surgical management of obesity among people with schizophrenia and bipolar disorder: a systematic review of outcomes and recommendations for future research. Obes Surg. 2017;27(7):1889–95. Narrative review to summarize the available knowledge on bariatric surgery in people with schizophrenia or bipolar disorder; growing evidence suggests that bariatric surgery may improve short-term weight status in these populations.PubMedCrossRef
126.
Hamoui N, Kingsbury S, Anthone GJ, Crookes PF. Surgical treatment of morbid obesity in schizophrenic patients. Obes Surg. 2004;14(3):349–52.PubMedCrossRef
127.
Ahmed AT, Warton EM, Schaefer CA, Shen L, McIntyre RS. The effect of bariatric surgery on psychiatric course among patients with bipolar disorder. Bipolar Disord. 2013;15(7):753–63.PubMedPubMedCentralCrossRef
128.
Shelby SR, Labott S, Stout RA. Bariatric surgery: a viable treatment option for patients with severe mental illness. Surg Obes Relat Dis. 2015;11(6):1342–8.PubMedCrossRef
129.
•• Agarwal SM, Stogios N, Ahsan ZA, Lockwood JT, Duncan MJ, Takeuchi H, et al. Pharmacological interventions for prevention of weight gain in people with schizophrenia. Cochrane Database Syst Rev. 2022(10). Cochrane systematic review of all available adjunctive pharmacological interventions for the prevention of AIWG; metformin is presently the best researched drug with the most evidence for this purpose.
130.
Hakami AY, Felemban R, Ahmad RG, Al-Samadani AH, Salamatullah HK, Baljoon JM, et al. The association between antipsychotics and weight gain and the potential role of metformin concomitant use: a retrospective cohort study. Front Psychiatry. 2022;13.
131.
•• Stogios N, Maksyutynska K, Navagnanavel J, Sanches M, Powell V, Gerretsen P, et al. Metformin for the prevention of clozapine-induced weight gain: a retrospective naturalistic cohort study. Acta Psychiatr Scand. 2022;146(3):190–200. Largest natrualistic retrospective cohort study to date demonstrating the effectiveness of cocomitant metformin in preventing clozapine-induced weight gain.PubMedCrossRef
132.
Rehan ST, Siddiqui AH, Khan Z, Imran L, Syed AA, Tahir MJ, et al. Samidorphan/olanzapine combination therapy for schizophrenia: efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials. Ann Med Surg. 2022;79:104115.CrossRef
133.
Correll CU, Newcomer JW, Silverman B, DiPetrillo L, Graham C, Jiang Y, et al. Effects of olanzapine combined with samidorphan on weight gain in schizophrenia: a 24-week phase 3 study. Am J Psychiatry. 2020;177(12):1168–78.PubMedCrossRef
134.
Correll CU, Stein E, Graham C, DiPetrillo L, Akerman S, Stanford AD, et al. Reduction in multiple cardiometabolic risk factors with combined olanzapine/samidorphan compared with olanzapine: post hoc analyses from a 24-week phase 3 study. Schizophr Bull. 2023;49(2):454–63.PubMedCrossRef
135.
Galderisi S, De Hert M, Del Prato S, Fagiolini A, Gorwood P, Leucht S, et al. Identification and management of cardiometabolic risk in subjects with schizophrenia spectrum disorders: a Delphi expert consensus study. Eur Psychiatry. 2021;64(1):e7.PubMedPubMedCentralCrossRef
136.
Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: aneEndocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342–62.PubMedCrossRef
Metadata
Title
Antipsychotic-Induced Weight Gain in Severe Mental Illness: Risk Factors and Special Considerations
Authors
Nicolette Stogios
Bailey Humber
Sri Mahavir Agarwal
Margaret Hahn
Publication date
27-09-2023
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 11/2023
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-023-01458-0

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