Medications for Alcohol Relapse and Cocaine Use
For alcohol relapse prevention, use naltrexone, acamprosate, or disulfiram as FDA-approved first-line agents; for cocaine dependence, no pharmacologic treatment can be recommended for primary care, though disulfiram shows promise and behavioral therapies remain the evidence-based standard. 1, 2, 3
Alcohol Use Disorder: Pharmacotherapy Options
FDA-Approved Medications for Alcohol Relapse Prevention
Three medications have FDA approval and should be offered to reduce relapse in alcohol-dependent patients:
Naltrexone (50 mg orally once daily or 380 mg IM monthly) blocks opioid receptors and dampens the reward pathway, reducing heavy drinking days and alcohol consumption. 2, 3 Patients must be completely detoxified and opioid-free for 7-10 days before initiation to avoid precipitated withdrawal. 3
Acamprosate (666 mg three times daily) is most effective for maintaining abstinence in already-detoxified patients, with high-quality evidence showing superiority over placebo. 2, 3 Treatment typically lasts 3-6 months and is the only intervention with high-quality evidence for maintaining abstinence. 2
Disulfiram (250 mg/day) is very effective in compliant patients but presents challenges in patient selection and requires reliable adherence. 4 It should be avoided in patients with severe alcoholic liver disease due to hepatotoxicity risk. 2
Off-Label Options with Evidence
- Baclofen (GABA-B receptor agonist) reduces alcohol craving and shows particular promise in patients with liver cirrhosis where naltrexone is contraindicated due to hepatotoxicity concerns. 2, 3, 5
Critical Alcohol Treatment Considerations
All patients with alcohol use disorder require thiamine supplementation (100-300 mg/day orally for prevention, 100-500 mg/day for treatment of Wernicke's encephalopathy) to prevent potentially fatal neurological complications. 2, 3 Thiamine must be administered before IV glucose-containing fluids to prevent acute thiamine deficiency. 3
Cocaine Dependence: Limited Pharmacologic Options
Evidence-Based Reality
Despite continued research efforts, no pharmacologic treatment for cocaine dependence can be recommended for use in the primary care setting. 1 This represents a critical gap in addiction medicine.
Behavioral Therapies as Standard of Care
Behavioral therapies have demonstrated effectiveness in the treatment of stimulant dependence and remain the evidence-based standard. 1
Investigational Pharmacologic Approaches
While not FDA-approved, three medications show potential in research settings:
Disulfiram shows the most promise among investigational agents. 5, 6 In patients with co-occurring cocaine and alcohol dependence, disulfiram (alone or combined with naltrexone) was most likely to achieve combined abstinence from both substances. 7 However, a 2024 Cochrane review found that disulfiram may increase point abstinence but may have little or no effect on frequency or amount of cocaine use. 6
Methylphenidate and modafinil are being studied but lack sufficient evidence for clinical recommendation. 5
Combined Alcohol and Cocaine Use: Treatment Algorithm
Step 1: Address Alcohol Dependence First
For patients with co-occurring alcohol and cocaine use:
Initiate disulfiram (250 mg/day) as it may address both substances. 7 Patients taking disulfiram were most likely to achieve combined abstinence from cocaine and alcohol. 7
Consider adding naltrexone (100 mg/day) to disulfiram. 7 The combination showed that more patients achieved 3 consecutive weeks of abstinence compared to placebo. 7
Step 2: Ensure Thiamine Supplementation
- Administer thiamine before any glucose-containing fluids. 3 High-risk patients (malnourished, severe withdrawal) require parenteral thiamine. 2, 3
Step 3: Integrate Psychosocial Support
Pharmacotherapy must be combined with psychosocial support, as medications alone are insufficient. 3 Cognitive-behavioral therapy plus pharmacotherapy shows superior outcomes compared to usual care plus pharmacotherapy. 3
- Encourage engagement with mutual help groups like Alcoholics Anonymous or Narcotics Anonymous. 1, 2, 3
Common Pitfalls to Avoid
Never start naltrexone during active withdrawal or before an adequate opioid-free period (7-10 days), as it can precipitate withdrawal. 3
Never withhold or delay thiamine administration in at-risk patients—Wernicke's encephalopathy is preventable but potentially fatal. 3
Never give glucose before thiamine in at-risk patients. 3
Never use naltrexone in patients with significant liver disease due to hepatotoxicity risk. 2, 3
Never prescribe medications without concurrent psychosocial support, as pharmacotherapy alone has limited efficacy. 3
Do not overlook concurrent substance use disorders that may complicate recovery. 2
Avoid prescribing benzodiazepines (if used for alcohol withdrawal) for longer than 7-14 days, as this increases dependence risk. 2
Referral Indications
Common indications for specialist referral include: