Medications for Alcohol Use Disorder Compared: Naltrexone, Acamprosate and Disulfiram

Three medications are FDA-approved to treat alcohol use disorder (AUD): naltrexone (as a daily pill or a monthly injection), acamprosate and disulfiram. Naltrexone and acamprosate are the ones the American Psychiatric Association recommends offering first for moderate to severe AUD; disulfiram is a more specialized choice for people committed to abstinence. Gabapentin and topiramate are used off-label when the first options do not fit.

All three approved medications are nonaddictive, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Yet very few people who could benefit receive one. This guide compares how each works, who it suits, the liver and kidney cautions, and how medication fits with therapy and mutual-help groups.

Why AUD medication is worth asking about

Federal survey data reported by NIAAA show how large the gap is. In 2024, about 28.0 million people ages 12 and older had AUD in the past year, but only 2.5%, or about 697,000 people, received medication for it. Only 7.6% received any alcohol use treatment at all.

AUD is diagnosed by counting symptoms over the past year, such as drinking more than intended, failed attempts to cut down, cravings, and continuing despite problems. NIAAA describes severity as mild with two to three criteria, moderate with four to five, and severe with six or more. The APA guideline's medication recommendations apply to moderate to severe AUD.

Medication does not replace the decision to change, and it is not a willpower test. It reduces craving, the reward of drinking, or the pull to drink again, which can make the work of therapy and recovery more manageable.

The approved medications side by side

Naltrexone

Oral naltrexone is indicated for alcohol dependence and for blocking the effects of opioids. The extended-release injectable form (Vivitrol) is indicated for alcohol dependence in people able to abstain in an outpatient setting before starting, and it should be part of a program that includes psychosocial support. The injection is 380 mg given into the buttock muscle by a healthcare provider every 4 weeks or once a month. A monthly injection removes the need to remember a daily pill, which some people find decisive.

In a large meta-analysis of outpatient trials, oral naltrexone at 50 mg a day was associated with less return to drinking: about 20 people needed to be treated to prevent one return to any drinking, and about 12 to prevent one return to heavy drinking. In the COMBINE trial, naltrexone given with medical management improved drinking outcomes. Because it blunts the reward of alcohol, naltrexone is often the choice for people whose goal is to cut down rather than stop entirely, although many use it to support abstinence.

Cautions

• Opioids: naltrexone is contraindicated in people taking opioid pain medicines, people physically dependent on opioids (including those on methadone or buprenorphine), and people in opioid withdrawal. The injectable label recommends at least 7 to 10 days free of opioids before starting.
• Overdose risk: after injectable naltrexone, opioid tolerance is reduced, and the label warns of potentially fatal overdose at the end of a dosing interval, after a missed dose, or after stopping.
• Liver: the labels report cases of hepatitis and clinically significant liver dysfunction. The APA recommends that naltrexone not be used in acute hepatitis or liver failure. Many people with AUD have some liver enzyme elevation, so prescribers check liver tests before and during treatment.
• Pain care: if you might need opioid pain relief, for example before planned surgery, tell every clinician you take naltrexone.
• Injection sites: Vivitrol injection site reactions can occasionally be severe enough to need surgery.

Acamprosate

Acamprosate is indicated to maintain abstinence in people with alcohol dependence who are abstinent when treatment begins, as part of a program with psychosocial support. The label states that its efficacy has not been shown in people who have not stopped drinking before starting, and that it does not eliminate or reduce withdrawal symptoms.

The recommended dose is 666 mg three times a day, which some people find hard to keep up. In the same meta-analysis, about 12 people needed to be treated with acamprosate to prevent one return to any drinking, and head-to-head trials found no significant difference between acamprosate and naltrexone. The COMBINE trial, by contrast, found no benefit of acamprosate over placebo, so the evidence is mixed.

Because acamprosate is cleared by the kidneys, the dose is reduced for moderate kidney impairment (creatinine clearance 30 to 50 mL/min) and it is contraindicated in severe impairment (30 mL/min or less). The APA recommends against using it first-line in mild to moderate kidney impairment. It does not depend on the liver, which makes it useful for people with liver disease. The label also asks that patients and families watch for depression or suicidal thoughts.

Disulfiram

Disulfiram works differently. It does not reduce craving; it makes drinking physically unpleasant. Even small amounts of alcohol can cause flushing, throbbing headache, nausea, vomiting, palpitations and a drop in blood pressure, and severe reactions can be life-threatening. The label warns that reactions can occur with alcohol up to 14 days after the last dose, and that hidden alcohol in sauces, cough mixtures and even aftershave can trigger them.

Its boxed warning states that it must never be given to someone who is intoxicated or without their full knowledge. It is contraindicated with severe heart disease, psychosis, and recent use of metronidazole or alcohol-containing products, and severe, sometimes fatal hepatitis has been reported, so liver tests are monitored. The APA suggests disulfiram for people with moderate to severe AUD whose goal is abstinence, who prefer it or have not done well on naltrexone and acamprosate, and who understand the risks of drinking on it. The APA training materials recommend involving a family member or roommate, with the person's agreement, as an observer of daily doses.

Off-label options: gabapentin and topiramate

The APA suggests topiramate or gabapentin for people with moderate to severe AUD who prefer them or who cannot take, or have not responded to, naltrexone and acamprosate. Neither is FDA-approved for AUD: gabapentin is approved for postherpetic neuralgia and as add-on treatment for certain seizures, and topiramate for epilepsy and migraine prevention.

The sibling guide on gabapentin and pregabalin in psychiatry covers gabapentin's wider uses and risks.

Medicines that are not AUD treatments

The APA recommends against using antidepressants to treat AUD itself unless there is a co-occurring condition for which an antidepressant is indicated, and against benzodiazepines except for alcohol withdrawal or another indicated condition. Mixing benzodiazepines and alcohol raises the risk of sedation, breathing problems and, in severe cases, death. For how alcohol interacts with other psychiatric prescriptions, see psychiatric medications and alcohol.

How a prescriber chooses

The APA suggests that drinking goals, whether abstinence, cutting down or other harm reduction, be agreed between patient and clinician and recorded. From there, the choice usually follows a few questions:

• Goal is to cut down, liver tests are acceptable, no opioid use: naltrexone is often first.
• Already abstinent, liver disease present, kidneys healthy: acamprosate may fit better.
• Uses or may need opioids: naltrexone is ruled out; acamprosate or an off-label option may be considered.
• Trouble remembering daily pills: injectable naltrexone.
• Firm abstinence goal and supervised dosing possible: disulfiram is an option.
• Pregnant or breastfeeding: the APA recommends against AUD medications except benzodiazepines for acute withdrawal or a co-occurring condition that warrants treatment, so this calls for specialist input.

Worked example: an adult who drinks heavily most evenings wants to cut back rather than quit, takes no opioids, and has mildly raised liver enzymes. A prescriber might discuss naltrexone with repeat liver tests, alongside counseling, and agree on a target such as fewer heavy drinking days. Someone else who has just finished a supervised withdrawal, has hepatitis and wants complete abstinence might be steered toward acamprosate if kidney function is normal. These sketches show how the factors interact; they are not recommendations for any individual.

What the evidence does not show: a clear winner between naltrexone and acamprosate overall, reliable predictors of who will respond to which medication, or much about combining them. Trying a second medication when the first does not help is reasonable.

The APA also recommends assessing co-occurring psychiatric and medical conditions that affect the choice. Depression and anxiety are common with heavy drinking, and some improve with sobriety while others need their own treatment. If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.

Never stop drinking abruptly after long, heavy use without medical advice: alcohol withdrawal can be dangerous and may need supervised management. Do not start, stop or change any of these medications on your own; route every change through your prescriber.

Medication plus therapy and mutual help

The APA recommends that every person with AUD have a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments. The labels for naltrexone injection and acamprosate state that they should be part of a program with psychosocial support. APA training materials list motivational enhancement therapy, CBT, medical management and community peer support groups as evidence-based nonpharmacological options with minimal harms.

Mutual-help groups add support at no cost. A Cochrane review of 27 studies found high-certainty evidence that manualized Alcoholics Anonymous and Twelve-Step Facilitation programs improve rates of continuous abstinence at 12 months compared with other established treatments such as CBT. Groups that are not Twelve-Step based also exist for people who prefer them. The sibling guide on group vs individual therapy compares formats.

When someone needs more structure than weekly visits, intensive outpatient, partial hospital or residential programs may help; see levels of mental health care. NIAAA's Alcohol Treatment Navigator helps people find quality care. If opioids are also involved, the guide to opioid use disorder treatment explains how treatment changes.

Questions to ask your prescriber

• Which medication fits my goal: cutting down or stopping completely?
• What liver and kidney tests do you need before I start, and how often will you repeat them?
• Do any of my current medications, including pain medicines, interact with this one?
• How soon should I notice a change, and how long would I take it?
• Who handles my therapy or counseling alongside the medication?
• What should I do if I drink while taking it?

How this practice approaches alcohol use

The site's substance use disorders page and the article on addiction recovery and integrative psychiatry describe the practice's approach. Its ongoing care includes psychiatric evaluation and medication management, psychotherapy including CBT and DBT, coaching, and lab testing. The practice is out of network with all insurance plans. A free discovery call is the place to ask whether the team is the right fit for your situation. Whether the practice's prescribers prescribe the medications in this guide, or manage alcohol withdrawal, is a question to ask on that call; withdrawal after long, heavy drinking may need a medically supervised setting. Some people with AUD are best served by an addiction specialist or a program; the guide on addiction psychiatrist vs general psychiatrist explains when. For more in this series, return to the Choosing Psychiatric Care guide.

Frequently asked questions

Can I drink while taking naltrexone?

Naltrexone does not cause a reaction with alcohol, and some treatment plans use it to help people cut down. Whether drinking at all is part of your plan is a decision to make with your prescriber, based on your goals and health.

Are AUD medications addictive?

No. NIAAA states that naltrexone, acamprosate and disulfiram are all nonaddictive. Gabapentin, used off-label, has been misused in some cases, mostly by people with other substance use, so prescribers screen for that risk.

How long do people take medication for alcohol use disorder?

There is no fixed duration. Trials often ran for several months, and many clinicians continue a medication that is working while recovery is consolidated. Stopping should be planned with the prescriber.

Can my primary care doctor prescribe these medications?

Yes. Naltrexone, acamprosate and disulfiram can be prescribed by any licensed prescriber, and the COMBINE trial showed naltrexone with medical management can be delivered in general health care settings. A specialist helps when there are complicating conditions.

What if I take opioid pain medicine or buprenorphine?

Naltrexone is contraindicated, because it blocks opioids and can trigger withdrawal. Acamprosate, and in some cases off-label options, may be considered instead. Tell every prescriber about all opioid use.

Is it safe to stop drinking on my own before starting medication?

Not always. After long, heavy drinking, alcohol withdrawal can be medically serious. Talk to a clinician before stopping so withdrawal can be assessed and managed safely; the APA guideline notes that benzodiazepines have a role in treating acute alcohol withdrawal.

Sources

1. Understanding Alcohol Use Disorder. National Institute on Alcohol Abuse and Alcoholism (NIH), 2025. niaaa.nih.gov
2. Alcohol Treatment in the United States. National Institute on Alcohol Abuse and Alcoholism (NIH), from 2024 NSDUH, 2025. niaaa.nih.gov
3. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder (training slides; Am J Psychiatry 2018;175(1):86-90). American Psychiatric Association, 2018. psychiatry.org
4. Naltrexone hydrochloride tablets prescribing information. DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov
5. Vivitrol (naltrexone for extended-release injectable suspension) prescribing information. Alkermes / DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov
6. Acamprosate calcium delayed-release tablets prescribing information. DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov
7. Disulfiram tablets prescribing information. DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov
8. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA (Jonas DE et al.), 2014. pubmed.ncbi.nlm.nih.gov
9. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295(17):2003-17 (Anton RF et al.), 2006. pubmed.ncbi.nlm.nih.gov
10. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Internal Medicine 174(1):70-7 (Mason BJ et al.), 2014. pubmed.ncbi.nlm.nih.gov
11. Neurontin (gabapentin) prescribing information. Viatris / DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov
12. Alcoholics Anonymous and other 12-step programs for alcohol use disorder. Cochrane Database of Systematic Reviews CD012880 (Kelly JF et al.), 2020. pubmed.ncbi.nlm.nih.gov
13. Topiramate tablets prescribing information. DailyMed, U.S. National Library of Medicine, 2026. dailymed.nlm.nih.gov

Educational information, not medical, tax or legal advice. Decisions about diagnosis, medication and treatment belong with a clinician who knows your history.