What is the role of ketamine in treating alcohol use disorder?

Ketamine for Alcoholism: Current Evidence and Applications

Ketamine is not currently FDA-approved for treating alcohol use disorder, though emerging research suggests it may have potential benefits when combined with psychotherapy, particularly for reducing alcohol consumption and cravings in the short term.

Current Evidence Base

Ketamine has been investigated for alcohol use disorder (AUD) with mixed results:

• Recent systematic reviews indicate promising but preliminary evidence for ketamine's efficacy in AUD treatment 1, 2
• A randomized controlled trial found that a single ketamine infusion (0.71 mg/kg) combined with motivational enhancement therapy significantly increased abstinence likelihood and delayed relapse compared to midazolam 3
• Older research from Russia reported that ketamine psychedelic therapy (KPT) showed 65.8% abstinence rates at one year versus 24% in conventional treatment 4

Mechanism and Administration

When used for AUD, ketamine is typically administered as:

• Intravenous infusion at subanesthetic doses (0.5-0.71 mg/kg) over 40-52 minutes 5, 3
• Usually provided as a single dose or limited series of infusions
• Often combined with psychotherapy (motivational enhancement therapy or other behavioral interventions) 3

The proposed mechanisms include:

• Disruption of addiction-related neural pathways
• Potential neuroplasticity effects that may help "reset" addictive patterns
• Psychedelic experiences that may facilitate psychological insights and behavioral change

Clinical Considerations

Potential Benefits

• May reduce alcohol cravings and consumption in the short term
• Could potentially delay relapse when combined with psychotherapy
• May benefit patients who have failed conventional treatments

Limitations and Risks

• Limited evidence base with mixed results across studies 1
• Potential for psychotomimetic effects (dysphoria, hallucinations) 5
• Risk of abuse must be considered, especially with domiciliary treatment 5
• Blood pressure monitoring essential due to potential transient increases 5
• Approximately 70% of responders may relapse by 4 weeks following the final infusion 5

Contraindications

• Uncontrolled cardiovascular disease
• Pregnancy
• Active psychosis
• Severe liver dysfunction
• High intracranial or ocular pressure 5

Current Best Practice Approach

1. Consider ketamine only after failure of first-line treatments:

   • FDA-approved medications (naltrexone, acamprosate, disulfiram)
   • Evidence-based psychotherapies (CBT, motivational enhancement)

2. Always combine with behavioral therapy:

   • Evidence supports combining pharmacotherapy with CBT or another evidence-based therapy rather than usual clinical management 6
   • Ketamine appears most effective when combined with psychotherapy 2, 3

3. Monitoring protocol:

   • Assess for cardiovascular effects during administration
   • Monitor for psychotomimetic side effects
   • Evaluate for at least 2 hours after administration 5
   • Implement regular follow-up to assess for relapse

Future Directions

More robust clinical trials are needed to determine:

• Optimal dosing strategies
• Long-term efficacy and safety
• Patient selection criteria
• Comparative effectiveness versus established treatments

While ketamine shows promise for AUD treatment, it should currently be considered an experimental approach rather than standard care until more definitive evidence emerges.