What medication options are available for a patient with alcohol use disorder (AUD) and major depressive disorder (MDD)?

Medication Options for Alcohol Use Disorder with Depression

For patients with alcohol use disorder and major depressive disorder, the most effective pharmacological approach is a combination of naltrexone (for alcohol dependence) and sertraline (for depression), which significantly improves both conditions compared to either medication alone or placebo.

First-Line Pharmacotherapy

For Alcohol Use Disorder

• Naltrexone (50-100 mg/day)
  • FDA-approved for alcohol dependence 1
  • Reduces heavy drinking days and cravings 2
  • Helps prevent relapse to heavy drinking (median delay of 98 days when combined with sertraline vs. 29 days with naltrexone alone) 3
  • Blocks euphoric effects of alcohol, reducing reward-based drinking 1

For Depression

• Sertraline (50-200 mg/day)
  • Effective for major depressive disorder 4
  • When combined with naltrexone, leads to higher rates of patients no longer meeting depression criteria by end of treatment (83.3%) 3
  • Female patients with alcohol dependence show particular improvement in depression symptoms with sertraline 5

Treatment Algorithm

1. Initial Phase (Weeks 1-2)

   • Begin naltrexone at 25 mg daily for 3 days, then increase to 50 mg daily
   • Start sertraline at 50 mg daily
   • Monitor for withdrawal symptoms using CIWA-Ar scale 6
   • For withdrawal management: benzodiazepines (preferably short-acting like oxazepam or lorazepam in patients with liver impairment) 2
   • Administer thiamine supplementation to prevent Wernicke's encephalopathy 2, 6

2. Stabilization Phase (Weeks 3-6)

   • Increase naltrexone to 100 mg daily if tolerated and needed 3
   • Titrate sertraline to 200 mg daily as needed for depression 3
   • Implement cognitive-behavioral therapy addressing both alcohol use and depression 3, 5

3. Maintenance Phase (Months 2-12)

   • Continue effective doses of both medications
   • Add psychosocial support through mutual help groups like Alcoholics Anonymous 2
   • Monitor liver function tests every 3-6 months with naltrexone 2

Alternative Medications

If naltrexone is contraindicated or poorly tolerated:

• Acamprosate (666 mg TID)
  • Safe in liver disease due to lack of hepatic metabolism 2, 6
  • Most effective for maintaining abstinence up to 12 months 2, 6
  • Does not interact with antidepressants 2

If sertraline is contraindicated or poorly tolerated:

• Other antidepressants may be considered, but evidence specifically for alcohol use reduction is limited 7

For patients with liver disease:

• Baclofen (starting at 5 mg TID)
  • Safer option for patients with hepatic impairment 2, 6
  • Improves abstinence rates and decreases relapse compared to placebo 6

Important Considerations

• Liver function: Naltrexone has been associated with hepatic injury at supratherapeutic doses; monitor liver function tests 2
• Medication interactions: Sertraline may increase bleeding risk when combined with NSAIDs or aspirin 4
• Contraindications: Disulfiram is contraindicated with sertraline liquid form due to alcohol content 4
• Withdrawal management: Benzodiazepines are first-line for alcohol withdrawal; antipsychotics should only be used as adjuncts for severe withdrawal delirium not responding to benzodiazepines 2

Monitoring and Follow-up

• Weekly visits during the first month, then biweekly for 2 months, then monthly
• Assess both alcohol use patterns and depressive symptoms at each visit
• Monitor for side effects, particularly GI symptoms, headache, and sexual dysfunction
• The combination of naltrexone and sertraline has shown fewer serious adverse events (11.9%) compared to either medication alone or placebo 3

The evidence strongly supports that addressing both conditions simultaneously with appropriate pharmacotherapy and psychosocial interventions leads to better outcomes than treating either condition alone.