Acamprosate for Alcohol Dependence
Acamprosate is the only medication with sufficient high-quality evidence to be recommended for maintaining abstinence in detoxified alcohol-dependent patients, and should be initiated 3-7 days after the last alcohol consumption once withdrawal symptoms have resolved. 1, 2, 3
Indication and Patient Selection
Acamprosate is indicated exclusively for maintenance of abstinence in patients who have already completed detoxification and achieved initial abstinence - it has not been demonstrated to be effective in patients who have not undergone detoxification or who are still drinking. 3, 4, 2
The drug works by modulating NMDA receptor transmission and restoring balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters, making it more effective for maintaining rather than inducing remission. 4, 5
Acamprosate increases the absolute probability of abstinence from 25% to 38% compared to placebo, with moderate certainty evidence - the strongest evidence base among all available medications for alcohol dependence. 2, 1
Dosing and Administration
The standard dose is 666 mg (two 333 mg tablets) three times daily, for a total of 1,998 mg per day. 3
Dosing Modifications:
Patients weighing <60 kg: Decrease dose by one-third. 4
Moderate renal impairment (CrCl 30-50 mL/min): Reduce to 333 mg three times daily. 3
Severe renal impairment (CrCl ≤30 mL/min): Contraindicated. 3
Dosing may be done without regard to meals, though dosing with meals was used in clinical trials and is suggested for patients who regularly eat three meals daily. 3
Timing of Initiation
Critical timing consideration: Start acamprosate 3-7 days after the last alcohol consumption, only after withdrawal symptoms have resolved - not immediately after sobering up. 4
Starting too early may reduce efficacy since the drug's primary mechanism is maintaining abstinence rather than inducing it. 4, 2
Treatment should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence. 3
Duration of Treatment
The typical treatment period is 3-6 months, but can extend up to 12 months. 4
Acamprosate should be maintained even if the patient relapses during treatment. 3
Weak evidence suggests potential effectiveness in the longer term beyond 12 months, though more research is needed. 1, 2
Comparative Effectiveness
Acamprosate demonstrates superior evidence quality compared to other FDA-approved medications for alcohol dependence:
Naltrexone and disulfiram: Insufficient high-quality evidence to conclude they improve abstinence in detoxified patients, despite being approved for this indication. 2, 1
Acamprosate reduces dropout rates from 50% to 42% compared to placebo, with moderate certainty evidence. 1, 2
The 2020 BMJ network meta-analysis identified acamprosate as the only intervention with moderate confidence in both effectiveness and acceptability up to 12 months. 1
Advantages in Special Populations
Acamprosate is uniquely suited for patients with alcoholic liver disease because it is not metabolized by the liver. 4, 5
Unlike naltrexone, acamprosate can be safely administered to patients with hepatitis or liver disease - a common comorbid condition in alcohol dependence. 5
The drug is not impacted by alcohol use, so can be continued even if the patient relapses. 5
Required Concurrent Treatment
Acamprosate must be used as part of a comprehensive psychosocial treatment program - it is not effective as monotherapy. 3, 4
All clinical trials demonstrating efficacy included concomitant psychosocial/behavioral therapies. 6, 7
The drug should not be used in isolation from psychosocial support. 4
Safety and Tolerability
Acamprosate has an excellent safety profile:
Most common adverse events are gastrointestinal (especially diarrhea) or dermatological, typically mild and transient. 6, 8
Withdrawal rates due to adverse events are similar to placebo. 6
Contains sodium sulfite, which may cause allergic-type reactions in sulfite-sensitive individuals (more common in asthmatics). 3
No evidence of abuse potential. 6
Low propensity for drug interactions. 8
Common Pitfalls to Avoid
Three critical errors that reduce treatment success:
Starting too early: Initiating immediately after sobering up rather than waiting 3-7 days post-detoxification reduces efficacy. 4
Omitting psychosocial support: Using acamprosate without concurrent psychosocial treatment is not supported by evidence. 4
Premature discontinuation: Stopping before 3-6 months prevents optimal results. 4