Predicting antipsychotic-induced weight gain in first episode psychosis-a protocol for a field-wide systematic review of prognostic factor studies

Ita Fitzgerald, Erin K. Crowley, Amy Byrne, Jean O’Connell, Joie Ensor, Ciara Ní Dhubhlaing, Sarah O'Dwyer, Laura J. Sahm


Background: One significant complexity associated with management of antipsychotic-induced weight gain (AIWG) is extensive interindividual variability amongst patients in initial susceptibility to AIWG, time to plateau of weight gain, and resultant final amount of weight gained. Prior to antipsychotic commencement, risk-stratified information highlighting those at increased risk of experiencing significant AIWG would allow tailored weight monitoring and subsequent management protocols to be developed.

Methods: This protocol is for a planned systematic review to identify the current utility of baseline clinical, sociodemographic, and biological prognostic factors in predicting the likelihood of significant AIWG occurring prior to antipsychotic commencement. The cohort assessed will be antipsychotic-naïve adults with a first episode of psychosis. Searches for both randomised and prospective non-randomised studies will be undertaken by searching four electronic databases and two trial registers, followed by reference searching, forward citation searching and liaison with content experts. A meta-analysis of study results will be undertaken where study quality and homogeneity allow. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework modified for prognostic research will be used to assess evidence certainty. This protocol was prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols guideline and latest guidance from the Prognosis Methods Group of the Cochrane Collaboration.

Results: This review will establish the current quantity, quality and clinical utility of evidence addressing the prognostic association of clinical, biological, and sociodemographic factors in prospectively identifying those more likely to experience significant AIWG.

Registration details: PROSPERO registration number CRD42021258148.


Antipsychotic-induced weight gain, Metabolic side effects, Antipsychotics, Risk factors, Prediction, Psychosis

Full Text:



Holt R. The Management of Obesity in People with Severe Mental Illness: An Unresolved Conundrum. Psychothe Psychosomatic. 2019;88(6):327-32.

Firth J, Siddiqi N, Koyanagi A, Siskind D, Rosenbaum S, Galletly C et al. The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness. Lancet Psychiatr. 2019;6(8):675712.

Raben AT, Marshe VS, Chintoh A, Gorbovskaya I, Müller DJ, Hahn MK. The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment. Frontiers Neurosci. 2018;11.

Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N et al. Comparative Efficacy and Tolerability of 32 Oral Antipsychotics for the Acute Treatment of Adults with Multi-Episode Schizophrenia: A Systematic Review and Network Meta-Analysis. Focus. 2020;18(4):443-55.

Bushe CJ, Slooff CJ, Haddad PM, Karagianis JL. Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database. J Psychopharmacol Oxf Engl. 2013;27(4):358-65.

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. World Psychiatr. 2019;18(1):53-66.

Saddichha S, Ameen S, Akhtar S. Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol. J Clin Psychopharmacol. 2008;28(1):27-31.

Carmona-Huerta J, Castiello-de Obeso S, Ramírez-Palomino J, Duran-Gutiérrez R, Cardona-Muller D, Grover-Paez F et al. Polypharmacy in a hospitalized psychiatric population: risk estimation and damage quantification. BMC Psychiatr. 2019;19(1).

Pandit R, Cianci D, Hark S, Winter-van Rossum I, Ebdrup BH, Broberg BV et al. Phenotypic factors associated with amisulpride‐induced weight gain in first‐episode psychosis patients (from the OPTiMiSE cohort). Acta Psychiatr Scandinavica. 2019;140(3):283-90.

Riley RD, Moons KGM, Snell KIE, Ensor J, Hooft L, Altman DG et al. A guide to systematic review and meta-analysis of prognostic factor studies. BMJ. 2019;364:k4597.

Zhang J, Lencz T, Zhang R, Masahiro N, Maayan L, Majnu J et al. Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis. Schizophrenia Bull. 2016;42(6):1418-37.

Reynolds G. Pharmacogenetic Aspects of Antipsychotic Drug-induced Weight Gain-A Critical Review. Clin Psychopharmacol Neurosci. 2012;10(2):71-7.

PRISMA 2021. Available at: Accessed on 11 June, 2021.

Introducing systematic reviews of prognosis studies to Cochrane: what and how? Cochrane Training. 2021. introducing-systematic-reviews-prognosis-studies-cochrane-what-and-how. Accessed on 14 June 2021.

Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre–post studies. Lancet Psychiatr. 2021;8(5):387-404.

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.

Ross R. Is setting a criterion for ‘clinically significant weight loss’ necessary? Obesity. 2016;24(4):791.

Keating D, McWilliams S, Schneider I, Hynes C, Cousins G, Strawbridge J et al. Pharmacological guidelines for schizophrenia: a systematic review and comparison of recommendations for the first episode. BMJ Open. 2017;7(1).

PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;(75):40-6.

Boulos L, Ogilvie R, Hayden J. Search methods for prognostic factor systematic reviews: a methodologic investigation. J Med Library Asso. 2021;1(109):23-32.

Hayden J, Van der Windt D, Cartwright JL, Cote P, Bombardier C. Assessing Bias in Studies of Prognostic Factors. Anna Internal Med. 2013;158(4):280-6.

Hruby A, Hu F. The Epidemiology of Obesity: A Big Picture. Pharmaco-economics. 2014;33(7):67389.

Riley R., Higgins J, and Deeks J. Interpretation of random effects meta-analyses. BMJ. 2011;10(342).

Langan D, Higgins J, Jackson D, Bowden J, Angeliki A, Kontopantelis E et al. A comparison of heterogeneity variance estimators in simulated random‐effects meta‐analyses. Res Synthesis Methods. 2018;10(1):83-98.

Peters J, Sutton A, Jones D, Abrams K, Rushton L. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol. 2008;61(10):991-6.

Hayden J, Wilson M, Riley R, Iles R, Pincus T, Ogilvie R. Individual recovery expectations and prognosis of outcomes in non-specific low back pain: prognostic factor review. Cochrane Database of Systematic Rev. 2019;11.

Foroutan F, Guyatt G, Zuk V, Vandvik PO, Alba AC, Mustafa R et al. GRADE Guidelines Use of GRADE for the assessment of evidence about prognostic factors: rating certainty in identification of groups of patients with different absolute risks. J Clin Epidemiol. 2020;121:62-70.

McMaster University. GRADEpro Guideline Development Tool. Version 1. 2020. Available at: Accessed on 3 February 2021.

Riley R, Hayden J, Steyerberg E, Moon KGM, Abrams K, Panayiotis AK et al. Prognosis Research Strategy (PROGRESS) 2: Prognostic Factor Research. PLoS Med. 2013;10(2).

Data citation