Gambling disorder (GD), often referred to as pathological gambling, is a serious psychiatric condition with significant repercussions for affected individuals and their communities. Despite its widespread impact, there is currently no pharmacological treatment officially approved for GD. However, a recent critical review published in Frontiers in Pharmacology by Bissig and Mutschler (2026) synthesises existing research on various off-label and investigational drugs, aiming to broaden clinicians’ understanding of potential pharmacological gambling disorder treatment options.
Understanding Gambling Disorder
Gambling is a common recreational activity globally, with a systematic review and meta-analysis by Tran et al. (2024) indicating that 46.2% of adults and 17.9% of adolescents have gambled in the past year. The prevalence of GD in the US and Europe is estimated between 0.42% and 1.3%, according to Loo et al. (2019) and Gabellini et al. (2023). GD is characterised by persistent and recurrent gambling behaviour that leads to significant impairment or distress, often resulting in severe financial debt, psychiatric comorbidities, impaired quality of life, and strained family relationships. A particularly concerning aspect is the high rate of suicidality associated with GD, with meta-analytic data suggesting that about one-third of individuals with gambling problems experience suicidal thoughts, and 13.2% have attempted suicide at least once (Kristensen et al., 2024).
While cognitive behavioural therapy (CBT) is considered an important and effective treatment, not all individuals achieve successful outcomes with CBT alone, highlighting the ongoing need for additional therapeutic strategies. The review by Bissig and Mutschler (2026) underscores that pharmacological interventions for GD remain off-label and experimental, with their use largely dependent on a physician’s clinical experience.
Investigating Pharmacological Gambling Disorder Treatment
The comprehensive review involved an electronic literature search in PubMed and a review of the ClinicalTrials.gov registry to identify open-label trials, randomised controlled trials, meta-analyses, and case reports related to investigational drug candidates for GD. The authors examined a wide array of substances, including selective serotonin reuptake inhibitors (SSRIs), opioid antagonists, mood stabilisers, and others.
Selective Serotonin Reuptake Inhibitors (SSRIs) in GD Treatment
SSRIs are commonly prescribed for conditions such as major depressive disorder, anxiety disorders, and obsessive-compulsive disorder (OCD). Although GD is now classified as a substance-related and addictive disorder in the DSM-V, it shares some phenomenological similarities with impulse control disorders and OCD, which have shown response to SSRIs. These medications work by inhibiting the presynaptic serotonin transporter, thereby enhancing serotonergic neurotransmission. Research suggests that serotonergic signalling may be altered in individuals with GD, pointing to a potential therapeutic role for SSRIs.
Fluvoxamine for Gambling Disorder
Several studies have explored fluvoxamine for GD. Hollander et al. (1998) reported promising outcomes in a short-term study, with 70% of participants achieving abstinence from gambling. A subsequent 16-week randomised, double-blind crossover trial by the same authors found significant improvement on the PG-CGI scale for fluvoxamine over placebo, though PG-YBOCS improvements did not reach statistical significance (Hollander et al., 2000). Limitations included small, male-only sample sizes and short follow-up periods.
Blanco et al. (2002) conducted a 6-month double-blind placebo-controlled study, finding fluvoxamine significantly superior in men and younger patients regarding time and money spent gambling, though overall differences were not statistically significant. This study also noted challenges with participant compliance and retention, and a high placebo response rate, which complicated the detection of significant differences. Dannon et al. (2005a) similarly found that fluvoxamine completers achieved remission of gambling behaviour, suggesting it may be particularly beneficial for individuals with predominant obsessive-compulsive symptoms.
A follow-up study by Dannon et al. (2007) observed relapse rates after fluvoxamine discontinuation, with 50% of responders relapsing within 6 months, though gambling losses remained lower than baseline. The authors hypothesised that the medication might induce lasting changes in neurotransmitter systems or neuromotivational pathways, or that extended periods of reduced gambling could lead to beneficial cognitive behavioural changes. Overall, available evidence from these studies indicates potential benefits of fluvoxamine in male individuals with GD during an acute phase of 8–12 weeks, particularly for those with co-occurring obsessive thoughts, compulsive behaviours, or depressive disorder. Further placebo-controlled, longer-term studies are needed to confirm long-term efficacy and optimal duration.
Paroxetine for Gambling Disorder
Kim et al. (2002) conducted an 8-week double-blind, placebo-controlled trial, observing significant improvements on the Clinical Global Impression Scale (CGI) and lower scores on the Gambling Symptom Assessment Scale (G-SAS) in the paroxetine group. Paroxetine was generally well tolerated. However, a subsequent multicenter randomised placebo-controlled trial by Grant et al. (2003) over 16 weeks, while showing greater improvements in the paroxetine group, only found statistical significance in the PG-YBOCS urge/thought subscale. Differences in placebo responder screening and gender distribution between studies may have influenced these varied outcomes, with a high placebo response rate potentially masking effects.
Future Directions in Gambling Disorder Treatment Research
The review highlights that while many investigational drugs, particularly opioid antagonists, have shown promising results in studies exploring aspects of GD, the small number of studies, inconsistent designs, and contradictory findings limit their clinical applicability. The authors emphasise the need for more robust, placebo-controlled studies with longer durations and investigations into specific patient subgroups to better understand the efficacy and optimal use of pharmacological interventions for gambling disorder.
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