Acamprosate

• Alcohol Use Disorder
• Alcohol Dependence
• Maintaining Sobriety

Acamprosate is a medication used in the treatment of alcohol use disorder to help maintain abstinence in patients who have stopped drinking. It works by helping to restore the brain's chemical balance disrupted by chronic alcohol use, reducing the discomfort and cravings associated with alcohol withdrawal.

Mechanism of Action

Acamprosate's exact mechanism of action is not fully understood, but it is thought to work by modulating glutamatergic neurotransmission. Chronic alcohol exposure causes adaptive changes in the brain, including upregulation of NMDA glutamate receptors and downregulation of GABA receptors. When alcohol use stops, the resulting glutamatergic hyperexcitability contributes to withdrawal symptoms and craving. Acamprosate is believed to act as a functional glutamate antagonist, reducing this hyperexcitability by interacting with both NMDA receptors and metabotropic glutamate receptors. It may also modulate calcium channels and enhance GABAergic inhibition, helping restore normal neuronal function.

Available Formulations

Acamprosate is available as enteric-coated, delayed-release tablets containing 333 mg of acamprosate calcium. The enteric coating protects the medication from stomach acid degradation and improves bioavailability. The tablets should be swallowed whole and not crushed, cut, or chewed.

Medical Uses

Acamprosate is FDA-approved for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. It is most effective when combined with psychosocial support programs including counseling, support groups, and behavioral therapy. The medication does not treat acute alcohol withdrawal and should not be used until withdrawal symptoms have resolved. Clinical trials have shown that acamprosate increases the proportion of patients maintaining complete abstinence and reduces drinking days in those who relapse.

Dosing Guidelines

The recommended dose is 666 mg (two 333 mg tablets) taken three times daily, for a total daily dose of 1998 mg. The medication may be taken with or without food, though taking with meals may help with adherence to the three-times-daily dosing schedule. Treatment should be initiated as soon as possible after withdrawal symptoms have subsided and abstinence has been achieved. Treatment duration is typically 12 months, though some patients may benefit from longer treatment. Dose reduction is required in patients with moderate renal impairment.

Important Safety Information

Acamprosate is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min). Patients with moderate renal impairment require dose reduction to 333 mg three times daily. The medication should be used with caution in patients with a history of depression or suicidal ideation, as depression and suicidal events have been reported. Unlike disulfiram, acamprosate does not produce an unpleasant reaction with alcohol consumption, so patients must be committed to abstinence.

Drug Interactions

Acamprosate has minimal drug interactions. It is not metabolized by the liver and does not inhibit or induce cytochrome P450 enzymes. Coadministration with naltrexone increases acamprosate exposure but dose adjustment is not required. The medication can be safely combined with antidepressants, anxiolytics, and other medications commonly used in patients with alcohol use disorder. Food decreases absorption but does not significantly affect overall efficacy when taken consistently.

Choosing Between Acamprosate, Naltrexone and Disulfiram

The three medications used in alcohol use disorder are not interchangeable, and they suit different moments. Naltrexone blunts the reward of drinking and can be started in someone who is still drinking, which makes it the usual first choice when the goal is to cut down before stopping. Acamprosate does something different: it is started after drinking has stopped, and it targets the prolonged unease of early abstinence — the restlessness, poor sleep, irritability, and low mood that persist for weeks after acute withdrawal has resolved and that account for a large share of returns to drinking. Disulfiram is a third, narrower option that depends on supervision.

Two practical features often settle the choice. Acamprosate is cleared by the kidneys rather than metabolized by the liver, so it remains available when liver disease or an ongoing opioid prescription makes naltrexone unsuitable — a common situation in this population. Conversely, kidney impairment restricts it, so kidney function is checked before the first prescription. The two medications can also be used together, and doing so is reasonable when one alone has been only partly effective.

Making Three Doses a Day Work

Six tablets a day is the main reason acamprosate fails, and adherence is worth planning rather than assuming. Anchoring the doses to meals, using a weekly organizer, and setting two phone alarms rather than three all help; the tablets are enteric coated and are swallowed whole rather than split or crushed. Loose stools in the first weeks are the usual early complaint and typically settle without stopping the drug.

Expectations need to be set as carefully as the schedule. Acamprosate produces nothing a patient can feel — there is no reaction if they drink, no blunting of a single drink, and no sensation of the medication working — so patients who are waiting for an effect conclude it is useless and stop. What it changes is measured over months, in days abstinent and in how manageable the background pull feels, and the honest framing is that it improves the odds rather than removing the decision. A lapse is a reason to continue, not to stop. Mood is monitored, since depression and suicidal thoughts have been reported and are also part of the underlying condition. The MedlinePlus acamprosate monograph and the NIAAA guide to understanding alcohol use disorder explain this for patients, our article on alcohol use disorder medications beyond AA compares the options, and our psychiatric team handles the counseling that roughly doubles what any of these medications achieve alone.

Special Populations

Acamprosate has not been adequately studied in pregnancy and should be used only if the potential benefit justifies the potential risk to the fetus. It is unknown whether acamprosate is excreted in human breast milk; caution should be exercised when administering to nursing mothers. Safety and efficacy have not been established in pediatric patients. Elderly patients with normal renal function do not require dose adjustment, though renal function should be assessed before starting therapy. Patients with hepatic impairment do not require dose adjustment.