Pharmacological management of gambling disorder: A systematic review and network meta-analysis

Konstantinos Ioannidis; Cinzia Del Giovane; Charidimos Tzagarakis; Jeremy E Solly; Samuel J Westwood; Valeria Parlatini; Henrietta Bowden-Jones; Jon E Grant; Samuele Cortese; Samuel R Chamberlain

doi:10.1016/j.comppsych.2024.152566

Pharmacological management of gambling disorder: A systematic review and network meta-analysis

Compr Psychiatry. 2024 Dec 10:137:152566. doi: 10.1016/j.comppsych.2024.152566. Online ahead of print.

Affiliations

¹ Department of Psychiatry, Faculty of Medicine, University of Southampton, UK and Hampshire and Isle of Wight Healthcare NHS Foundation Trust, Southampton, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK. Electronic address: k.ioannidis@soton.ac.uk.
² Department of Medical and Surgical Sciences for Children and Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy and Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
³ Department of Psychiatry, School of Medicine, University of Crete, Iraklion, Greece, Organization Against Drugs (OKANA), Athens, Greece and Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States.
⁴ Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK; Department of Psychiatry, University of Cambridge, UK.
⁵ Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶ CIMH, School of Psychology, University of Southampton, Southampton, UK; Hampshire and Isle of Wight NHS Foundation Trust, UK; Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷ National Problem Gambling Clinic & National Centre for Gaming Disorders, London, UK; and Department of Psychiatry, University of Cambridge, UK Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
⁸ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
⁹ Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; DiMePRe-J-Department of Precision and Rigenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy; Department of Child and Adolescent Psychiatry, New York University Grossman School of Medicine, New York, USA.
¹⁰ Department of Psychiatry, Faculty of Medicine, University of Southampton, UK and Hampshire and Isle of Wight Healthcare NHS Foundation Trust, Southampton, UK.

PMID: 39675219
DOI: 10.1016/j.comppsych.2024.152566

Abstract

Background: Clinical guidelines remain unclear on which medications for gambling disorder are to be preferred in terms of efficacy and tolerability. We aimed to compare pharmacological treatments for gambling disorder in terms of efficacy and tolerability, using network meta-analysis (NMA).

Methods: Based on our pre-registered protocol [CRD42022329520], a structured search was conducted across broad range of databases, for double-blind randomized controlled trials (RCTs) of medications for gambling disorder. Data were independently extracted by two researchers. We used standardized mean differences (SMD) using Hedges' g to measure the efficacy outcomes, and for the effect for tolerability we used dropout rate due to medication side effects, expressed as odds ratio (OR). Confidence in the network estimates was assessed using the CINeMA framework. We followed the PRISMA-NMA guidelines for this work. Outcomes were gambling symptom severity and quality of life (for efficacy), and tolerability.

Findings: We included 22 RCTs in the systematic review and 16 RCTs (n = 977 participants) in the NMA. Compared with placebo, moderate confidence evidence indicated that nalmefene [Standardized Mean Difference (SMD): -0.86; 95 % confidence interval (CI: -1.32,-0.41)] reduced gambling severity, followed by naltrexone (SMD: -0.42; 95 %CI: (-0.85,0.01)). Naltrexone (SMD: -0.50; 95 %CI: (-0.85,-0.14)) and nalmefene (SMD: -0.36; 95 %CI: (-0.72,-0.01) were also more beneficial than placebo in terms of quality of life. Olanzapine and topiramate were not more efficacious than placebo. Nalmefene [Odds Ratio (OR): 7.55; 95 %CI: (2.24-25.41)] and naltrexone (OR: 7.82; 95 %CI: (1.26-48.70)) had significantly higher dropout due to side effects (lower tolerability) compared with placebo.

Interpretation: Based on NMA, nalmefene and naltrexone currently have the most supportive evidence for the pharmacological treatment of gambling disorder. Further clinical trials of novel compounds, and analysis of individual participant data are needed, to strengthen the evidence base, and help tailor treatments at the individual patient level.

Keywords: Gambling; Network meta-analysis; Pharmacotherapy; treatment.