Background: Guidelines remain unclear on which medications for gambling disorder are to be preferred in terms of efficacy and tolerability. Aims: To compare pharmacological treatments for gambling disorder with each other and placebo on efficacy and tolerability, using network meta-analysis (NMA). Methods: We searched a broad range of databases for double-blind randomized controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy); as well as tolerability. Confidence in the network estimates was assessed using the CINeMA framework. Results: We included 21 RCTs in the systematic review and 15 RCTs (n = 940 participants) in the NMA. Compared with placebo, high confidence evidence indicated that nalmefene [Standardized Mean Difference (SMD): -0.87; 95% confidence interval (CI: -1.33,-0.41)] reduced gambling severity, followed by naltrexone [-0.43; -0.83,-0.02)]. Nalmefene [Odds Ratio (OR): 7.55; 95%CI: 2.24-24.41] and naltrexone (7.82; 1.26-48.70) had significantly higher dropout (lower tolerability) compared with placebo. As compared with placebo, naltrexone (SMD: -0.49; 95%CI: -0.81,-0.18) and nalmefene (-0.36; -0.72,-0.01) were beneficial in terms of quality of life. Conclusions: Nalmefene and naltrexone currently have the most supportive evidence for the pharmacological treatment of gambling disorder. Further clinical trials are needed, as well as analysis of individual participant data, to strengthen and broaden the evidence base, and to help tailor treatments at the individual patient level.

The authors have declared no competing interest.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329520

This study was supported by unrestricted grant funds to Professor Chamberlain held at the University of Southampton, originating from the NHS. The funding source had no role in the design, conduct, or reporting of the study.

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This is a network meta-analysis (NMA). Data were exctracted from the relevant papers which are cited in the manuscript. Ethics approvals are described in each individual paper.

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All data produced in the present study are available upon reasonable request to the authors