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. SEARCH METHODS: 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).
SELECTION CRITERIA: 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%).
AUTHORS' CONCLUSIONS: 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.