Background
Gambling problems can lead to severe consequences for gamblers, their family members and friends, and the community. A range of medications are used to treat people with gambling problems, but there are few high-quality reviews of the research evidence to guide which ones should be used in practice.
Review question
We investigated whether different types of medications are effective in reducing gambling symptoms compared to no treatment (i.e. placebo, or dummy treatment) or other types of medications.
Study characteristics
We included randomised trials (gold-standard trials for evaluating the effectiveness of treatments where participants are randomly assigned to one of two or more treatments) published before January 2022. We included 17 studies in the review with a total of 1193 participants. These studies compared antidepressants (medications used to prevent or treat depression), opioid antagonists (medications that reverse and block the effects of opioids like pain relievers and heroin; e.g., naltrexone, nalmefene), mood stabilisers (medications that treat and prevent highs (mania) and lows (depression)), and atypical antipsychotics (medications used to treat schizophrenia or to help treat other psychiatric disorders) with either a no-treatment control group (i.e. placebo) or with each other. We explored the effectiveness of these treatments on a range of outcomes: gambling symptom severity, gambling expenditure, gambling frequency, depressive symptoms, anxiety symptoms, functional impairment (limitations due to the illness), and responder status (i.e. positive response to treatment based on gambling symptoms or behaviour, or both).
Key results
Antidepressants: We combined the results of six studies (268 participants) investigating the effectiveness of antidepressants. At the end of treatment, there were no clear differences between antidepressants and no treatment on any measure where there was more than one available study: gambling symptom severity, gambling expenditure, depressive symptoms, functional impairment, or responder status.
Opioid antagonists: We combined the results of four studies (562 participants) investigating the effectiveness of opioid antagonists. More than one study evaluated gambling symptom severity and responder status. At the end of treatment, these medications were more helpful than no treatment in improving gambling symptom severity, but there were no clear differences in terms of responder status.
Mood stabilisers: We combined the results of two studies (71 participants) investigating the effectiveness of medications with mood-stabilising properties. At the end of treatment, there were no clear differences between mood stabilisers and no treatment on any measure where there was more than one available study: gambling symptom severity, depressive symptoms, or anxiety symptoms.
Atypical antipsychotics: We combined the results of two studies (63 participants) investigating the effectiveness of the atypical antipsychotic olanzapine. At the end of treatment, this medication was more helpful than no treatment in reducing gambling symptom severity.
Comparisons between medications: We identified very few studies that compared the effectiveness of different types of medications. Two studies compared antidepressants with opioid antagonists; two studies compared antidepressants with mood stabilisers; and one study compared opioid antagonists and mood stabilisers. At the end of treatment, there were no clear differences between any of these medications on any measure.
Adverseeffects: Several common adverse effects (side effects) were reported by people receiving antidepressants (e.g. headaches, nausea, diarrhoea/gastrointestinal issues) and opioid antagonists (e.g. nausea, dry mouth, constipation). Adverse effects reported by people receiving mood stabilisers (e.g. tiredness, headaches, concentration difficulties) or atypical antipsychotics (e.g. pneumonia, sedation, elevated mood) were not consistent. Those most likely to stop treatment due to adverse effects were receiving opioid antagonists, followed by antidepressants, atypical antipsychotics, and mood stabilisers.
Quality of evidence
Only a limited number of studies with a small number of participants investigated the effectiveness of each type of medication. We considered the quality of the evidence across most of the outcomes in this review as very low or low, meaning that we are uncertain about the results.
Conclusion
Based on a small amount of low-quality evidence, we conclude that opioid antagonists and atypical antipsychotics (but seemingly not antidepressants) may be effective in reducing gambling symptom severity. There was insufficient information to determine whether these medications can improve other gambling and psychological symptoms. The results relating to mood stabilisers are uncertain. We do not know how effective these medications are in the long term. More research is needed before we can draw any firm conclusions about the effectiveness of medications for gambling problems.
This review provides preliminary support for the use of opioid antagonists (naltrexone, nalmefene) and atypical antipsychotics (olanzapine) to produce short-term improvements in gambling symptom severity, although a lack of available evidence precludes a conclusion regarding the degree to which these pharmacological agents can improve other gambling or psychological functioning indices. In contrast, the findings are inconclusive with regard to the effects of mood stabilisers (including anticonvulsants) in the treatment of disordered or problem gambling, and there is limited evidence to support the efficacy of antidepressants. However, these conclusions are based on very low to low certainty evidence characterised by a small number of included studies, high risk of bias, modest pooled sample sizes, imprecise estimates, moderate between-study heterogeneity, and exclusion of participants with psychiatric comorbidities. Moreover, there were insufficient studies to conduct meta-analyses on many outcome measures; to compare efficacy across and within major categories of interventions; to explore dosage effects; or to examine effects beyond post-treatment. These limitations suggest that, despite recommendations related to the administration of opioid antagonists in the treatment of disordered or problem gambling, pharmacological interventions should be administered with caution and with careful consideration of patient needs. A larger and more methodologically rigorous evidence base with longer-term evaluation periods is required before definitive conclusions can be drawn about the effectiveness and durability of pharmacological treatments for disordered or problem gambling.
Pharmacological interventions for disordered and problem gambling have been employed in clinical practice. Despite the availability of several reviews of the efficacy of pharmacological interventions for disordered or problem gambling, few have employed systematic search strategies or compared different categories of pharmacological interventions. Systematic reviews of high-quality evidence are therefore essential to provide guidance regarding the efficacy of different pharmacological interventions for disordered or problem gambling.
The primary aims of the review were to: (1) examine the efficacy of major categories of pharmacological-only interventions (antidepressants, opioid antagonists, mood stabilisers, atypical antipsychotics) for disordered or problem gambling, relative to placebo control conditions; and (2) examine the efficacy of these major categories relative to each other.
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and PsycINFO (all years to 11 January 2022).
We included randomised trials evaluating a pharmacological intervention for the treatment of disordered or problem gambling. Eligible control conditions included placebo control groups or comparisons with another category of pharmacological intervention.
We used standard methodological procedures, including systematic extraction of included study characteristics and results and risk of bias assessment. Our primary outcome was reduction in gambling symptom severity. Our secondary outcomes were reduction in gambling expenditure, gambling frequency, time spent gambling, depressive symptoms, anxiety symptoms, and functional impairment; and responder status. We evaluated treatment effects for continuous and dichotomous outcomes using standardised mean difference (SMD) and risk ratios (RR), respectively, employing random-effects meta-analyses. A minimum of two independent treatment effects were required for a meta-analysis to be conducted (with only meta-analytic findings reported in this abstract).
We included 17 studies in the review (n = 1193 randomised) that reported outcome data scheduled for end of treatment. Length of treatment ranged from 7 to 96 weeks.
Antidepressants: Six studies (n = 268) evaluated antidepressants, with very low to low certainty evidence suggesting that antidepressants were no more effective than placebo at post-treatment: gambling symptom severity (SMD −0.32, 95% CI −0.74 to 0.09, n = 225), gambling expenditure (SMD −0.27, 95% CI −0.60 to 0.06, n = 144), depressive symptoms (SMD −0.19, 95% CI −0.60 to 0.23, n = 90), functional impairment (SMD −0.15, 95% CI −0.53 to 0.22, n = 110), and responder status (RR 1.24, 95% CI 0.93 to 1.66, n = 268).
Opioid antagonists: Four studies (n = 562) evaluated opioid antagonists, with very low to low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD −0.46, 95% CI −0.74 to −0.19, n = 259), but no difference between groups in responder status (RR 1.65, 95% CI 0.86 to 3.14, n = 562).
Mood stabilisers: Two studies (n = 71) evaluated mood stabilisers (including anticonvulsants), with very low certainty evidence suggesting that mood stabilisers were no more effective than placebo at post-treatment: gambling symptom severity (SMD −0.92, 95% CI −2.24 to 0.39, n = 71), depressive symptoms (SMD −0.15, 95% CI −1.14 to 0.83, n = 71), and anxiety symptoms (SMD −0.17, 95% CI −0.64 to 0.30, n = 71).
Atypical antipsychotics: Two studies (n = 63) evaluated the atypical antipsychotic olanzapine, with very low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD −0.59, 95% CI −1.10 to −0.08, n = 63).
Comparative effectiveness: Two studies (n = 62) compared antidepressants with opioid antagonists, with very low certainty evidence indicating that antidepressants were no more effective than opioid antagonists on depressive symptoms (SMD 0.22, 95% CI −0.29 to 0.72, n = 62) or anxiety symptoms (SMD 0.21, 95% CI −0.29 to 0.72, n = 62) at post-treatment. Two studies (n = 58) compared antidepressants with mood stabilisers (including anticonvulsants), with very low certainty evidence indicating that antidepressants were no more effective than mood stabilisers on depressive symptoms (SMD 0.02, 95% CI −0.53 to 0.56, n = 58) or anxiety symptoms (SMD 0.16, 95% CI −0.39 to 0.70, n = 58) at post-treatment.
Tolerability and adverse events: Several common adverse effects were reported by participants receiving antidepressants (e.g. headaches, nausea, diarrhoea/gastrointestinal issues) and opioid antagonists (e.g. nausea, dry mouth, constipation). There was little consistency in the types of adverse effects experienced by participants receiving mood stabilisers (e.g. tiredness, headaches, concentration difficulties) or atypical antipsychotics (e.g. pneumonia, sedation, increased hypomania). Discontinuation of treatment due to these adverse events was highest for opioid antagonists (10% to 32%), followed by antidepressants (4% to 31%), atypical antipsychotics (14%), and mood stabilisers (13%).