Pharmacologic Treatment for Alcohol Craving
Acamprosate is the first-line medication for treating alcohol craving and maintaining abstinence in detoxified patients, as it is the only intervention with sufficient high-quality evidence demonstrating both effectiveness and acceptability. 1, 2
Primary Recommendation: Acamprosate
Acamprosate should be prescribed at 666 mg (two 333 mg tablets) three times daily for patients ≥60 kg who have already achieved detoxification and abstinence. 3
Evidence Supporting Acamprosate
Acamprosate increases the absolute probability of maintaining abstinence from 25% (placebo) to 38%, with moderate certainty evidence (OR 1.86,95% CI 1.49-2.33). 1
It demonstrates superior acceptability compared to placebo, reducing dropout rates from 50% to 42% (OR 0.73,95% CI 0.62-0.86), with moderate certainty evidence. 1
The American College of Physicians recommends acamprosate as the only intervention with sufficient high-quality evidence for maintaining abstinence in detoxified alcohol-dependent patients. 2
Acamprosate is more effective at maintaining abstinence rather than inducing remission, making it appropriate only after detoxification is complete. 2
Dosing Algorithm for Acamprosate
Standard dose: 666 mg (two 333 mg tablets) three times daily for patients ≥60 kg 3
Reduced dose: Decrease by one-third for patients <60 kg 3
Renal impairment: 333 mg three times daily for moderate renal impairment (CrCl 30-50 mL/min) 3
Duration: Continue for 3-6 months minimum, up to 12 months 3
Critical Timing Consideration
Do not start acamprosate until the patient has completed detoxification and achieved abstinence. 2, 3 The drug has not been shown to have significant impact on patients who have not been detoxified, as its mechanism works best for maintaining rather than achieving abstinence. 3
Alternative Option: Naltrexone
Naltrexone (50 mg once daily) can be considered as a second-line option, but the evidence is weaker than for acamprosate. 1
When to Use Naltrexone
Naltrexone is recommended for patients aiming to cut down their alcohol intake rather than maintain complete abstinence. 4
It reduces the likelihood of return to any drinking by 5% and binge-drinking risk by 10%. 5
Naltrexone reduces alcohol craving and the pleasurable "high" while drinking through opioid receptor blockade. 6
Critical Contraindications for Naltrexone
Never use naltrexone in patients with severe liver disease or hepatic insufficiency. 3, 7 The European Association for the Study of Liver Diseases explicitly states that naltrexone is contraindicated in alcoholic liver disease due to documented hepatocellular injury risk. 3
Do not use naltrexone in patients taking opioids, as it will precipitate narcotic withdrawal. 6
Naltrexone Limitations
Hepatotoxicity occurs at dosages much higher than the standard 50 mg daily dose, but caution is warranted in any liver disease. 6
The evidence for naltrexone maintaining abstinence in detoxified patients is insufficient and of lower quality compared to acamprosate. 1
Combination Therapy
The combination of acamprosate and naltrexone showed improved abstinence versus placebo (OR 3.68,95% CI 1.50-9.02), but this is based on low-quality evidence from limited studies. 1, 7
Medications NOT Recommended as First-Line
Disulfiram is no longer considered first-line treatment due to difficulties with compliance, toxicity, and lack of high-quality evidence supporting its use in maintaining abstinence. 1, 4
Other medications (topiramate, baclofen, pregabalin) have some evidence of benefit but are not FDA-approved for alcohol dependence and should only be considered in specialist practice. 4
Special Population: Patients with Liver Disease
Acamprosate is the preferred and only safe pharmacotherapy for alcohol dependence in patients with liver disease because it is not metabolized by the liver and carries no hepatotoxicity risk. 3, 7
Check AST, bilirubin, and platelet levels before initiating treatment. 3
Determine if hepatic insufficiency or cirrhosis is present using non-invasive methods (FibroScan, FibroTest, or FibroMeter Alcohol). 3
Avoid naltrexone and disulfiram in severe liver disease due to hepatotoxicity risk. 3
Essential Adjunctive Treatment
Acamprosate must be combined with comprehensive psychosocial treatment and counseling for optimal efficacy. 3 Medication alone is insufficient; it should be part of a comprehensive treatment plan that includes behavioral interventions. 4, 5