What is the best medication for treating co-occurring gambling disorder and substance use disorder?

Best Medication for Co-Occurring Gambling and Substance Use Disorder

Naltrexone is the medication of choice for treating co-occurring gambling disorder and substance use disorder, as it has the strongest evidence for reducing both gambling urges and substance use behaviors by targeting shared dopaminergic reward pathways. 1, 2

Primary Pharmacological Recommendation

Naltrexone should be prescribed as first-line pharmacotherapy for patients with both gambling disorder and substance use disorder, given its dual efficacy profile. 1, 2, 3

• Mechanism: Naltrexone blocks opioid receptors, reducing dopamine release in the nucleus accumbens that sustains both gambling and substance use behaviors. 2
• Evidence strength: Opioid antagonists like naltrexone have the most robust evidence among all medications studied for gambling disorder. 2, 3, 4
• Dual benefit: Naltrexone is FDA-approved for both opioid use disorder and alcohol use disorder, while simultaneously showing the strongest evidence for reducing gambling urges and behaviors. 5, 6

Critical Treatment Principle: Never Use Medication Alone

Naltrexone must always be combined with cognitive behavioral therapy (CBT), never prescribed as monotherapy. 1, 2

• CBT has the strongest evidence base for gambling disorder and should be the initial treatment approach, targeting gambling-specific cognitive distortions. 1
• Pharmacotherapy combined with CBT shows greater efficacy than medication alone, with CBT improving responses that plateau with medication-only treatment. 1, 5
• Add motivational interviewing (MI) to CBT for patients ambivalent about change, which is common in dual-diagnosis presentations. 1, 4

Addressing Comorbidities Systematically

Screen and treat co-occurring psychiatric conditions, as gambling disorder frequently presents with ADHD, impulse control problems, compulsive symptoms, and multiple substance use disorders. 7, 1, 2

• The shared neurobiology involves abnormalities in brain reward pathways (striatum) and loss of prefrontal cortex control over urges. 7
• Despite clinical parallels, differences are emerging between gambling disorder and alcohol use disorder brain patterns, suggesting overlapping but distinct pathophysiology. 7

Alternative Pharmacological Options

If naltrexone is contraindicated or ineffective:

• Nalmefene (another opioid antagonist) shows promising results similar to naltrexone. 6
• Topiramate (mood stabilizer) has shown some efficacy in reducing gambling symptoms. 6, 4
• Lithium is particularly effective for patients with comorbid bipolar disorder. 4

Important Clinical Caveat

Be vigilant in Parkinson's disease patients on dopaminergic medications, as they have increased risk of developing gambling disorder and impulse control problems. 1, 2

• This population requires careful monitoring and may need medication adjustments rather than adding naltrexone. 7

Treatment Sequencing Algorithm

1. Initiate naltrexone (50-100mg daily for opioid use disorder; 50mg daily for alcohol use disorder) 5
2. Simultaneously begin structured CBT targeting both gambling-specific cognitive distortions and substance use triggers 1
3. Add motivational interviewing if patient shows ambivalence about treatment engagement 1, 4
4. Screen for and treat comorbid psychiatric conditions (ADHD, mood disorders, other impulse control problems) 1, 2
5. Monitor response at 4-6 weeks and adjust treatment intensity based on gambling frequency, financial losses, and substance use patterns 4

Common Pitfalls to Avoid

• Never prescribe naltrexone without concurrent behavioral therapy, as monotherapy has poor outcomes. 1, 2
• Do not withhold naltrexone due to concerns about drug interactions with HIV or hepatitis C treatments in patients with substance use disorders. 5
• Avoid focusing solely on abstinence rather than harm reduction approaches, particularly early in treatment. 5
• Do not ignore the high placebo response rates seen in gambling disorder trials when interpreting individual patient responses. 6