The Best Way to Treat Alcohol Use Disorder (AUD)

Patients prescribed glucagon-like peptide 1 receptor agonists (GLP-1RAs) G for obesity were found to drink and crave less alcohol. The first research clinical trial showed that low-dose semaglutide can reduce craving and reduce drinking in alcohol abuse disorder (AUD), justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder. Randomized clinical trials and comparable efficacy of Ozempic should help us understand where this potential new treatment fits compared to existing older treatments for AUD. Disulfiram, often known by the brand name Antabuse, was approved by the FDA in 1951 as a first-line treatment for patients with AUD. Most physicians today don't prescribe it because it is often assumed that patient compliance is poor: If the patient taking the drug consumes any alcohol, it causes copious vomiting.

However, Stephen R. Holt, M.D., Director of Yale University's Addiction Recovery Clinic, does not agree. “Recently," he points out, "there were shortages of disulfiram. I have been very surprised to find patients spent countless hours looking and looking and finding disulfiram in Canada or Europe or elsewhere and continued taking their medication despite repeated obstacles.”

Disulfiram is safe, effective, and life-saving for patients with AUD who do not want to drink any alcohol, Holt told me. “If abstinence is the goal of treatment, then disulfiram is my first choice. The patient must agree and understand the side effects and risk-benefits.” He added, “I have had so much success treating patients with disulfiram!” In some cases, disulfiram was life-saving, reversing what seemed like untreatable AUD. A person's fear of the aversive effects of the disulfiram-alcohol interaction can be a deterrent for some patients. Disulfiram is considered a second-line option by most physicians, with naltrexone being most widely prescribed and naltrexone and acamprosate serving as first-line options.

30 Years After Naltrexone’s Approval

Naltrexone is an opioid receptor antagonist approved by the FDA in 1995 for treating alcohol dependence as an oral preparation and, in 2006, as a long-acting injectable. Naltrexone blocks the reward or buzz of opioids or alcohol, with one daily pill. Because many patients didn’t take their naltrexone pill as prescribed, injectable naltrexone was developed. Ozempic may have better adherence but still reduces drinking like naltrexone and may also reduce cigarette smoking and weight too.

Patients report naltrexone takes most of the fun out of alcohol, preventing binge drinking and reducing drinking. If the goal is drinking less rather than quitting altogether, naltrexone certainly helps individuals regain control by making alcohol less appealing.

Acamprosate (calcium homotaurine)

The newest treatment for AUD, acamprosate (Campral) was developed in France. The FDA approved the drug for abstinence maintenance in detoxified alcoholics 21 years ago, in 2004. Acamprosate restores the glutamate-related brain systems that are abnormal in patients with AUD, especially during acute and prolonged withdrawal. Like naltrexone, it works if taken to reduce drinking and craving and to reduce harm produced by drinking. It is not metabolized by the liver but is excreted primarily by the kidney. Its use is contraindicated in patients with severe renal impairment.

The Debate: Antabuse or Naltrexone

There is definitive research regarding the benefits of medications for AUD, but which treatment is better and for whom? The American Society of Addiction Medicine’s official Journal of Addiction Medicine featured a paper by Dr. Holt in the November/December 2024 issue. He recommended rejecting the idea that acamprosate or naltrexone must be a first-line treatment; instead, he proposes using disulfiram as a first-line treatment.

Holt argues that supervised disulfiram is a viable and effective first-line treatment for many patients with AUD. Supervised administration ensures adherence, crucial for disulfiram’s efficacy. Holt also emphasizes patient selection: Ideal candidates are motivated toward abstinence, have a supportive environment, and can commit to regular supervision. He addresses hepatotoxicity concerns, noting that risks are manageable with proper patient selection and monitoring.

In contrast, Sarah Axelrath, an addiction specialist trained at Massachusetts General Hospital (MGH) and currently at the Colorado Coalition for the Homeless in Denver, argues that disulfiram should not be a first-line treatment for AUD. She acknowledges disulfiram can be effective for patients highly motivated toward abstinence who have no medical or psychiatric contraindications and who possess strong family support. But she recommends other FDA-approved medications as first-line options, reserving disulfiram for rare cases when potential benefits outweigh the risks.

Other Drugs Sometimes Used Off-Label for AUDS

Although disulfiram, naltrexone, and acamprosate are the only medications approved by the FDA for AUD, other drugs are sometimes prescribed off-label. For example, the epilepsy medicine topiramate or semaglutide, the active ingredient in Ozempic and Wegovy, may help people drink less alcohol. Glucagon-like peptide-1- 1 (GLP-1) drugs such as Ozemmpic are commonly prescribed for diabetes management and weight loss, which may provide patients with an incentive to take the drug as prescribed. it would be good news to have a new treatment for alcohol harm reduction, that patients would want to take. More research is needed comparing GLP-1 medications to drugs FDA-approved for alcohol use disorder.

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Alcoholics Anonymous

Millions of people attend Alcoholics Anonymous (AA) meetings, and millions have successfully stopped drinking with the help of AA. AA is the most popular treatment option with people with AUD. AA meetings are widely available around the U.S., are free, and the program provides role models and sponsors to help others around the clock. However, not everyone likes AA, and there is considerable variability among meetings. However, AA works.

Cochrane Review co-author Dr. John Kelly at Harvard's MGH says their review shows AA helps people shift their social networks away from heavy drinkers and toward people in recovery. That's what professional therapy tries to do, he observes, but AA does it in a more accessible and obviously less expensive way. For example, 42% of AA participants were completely abstinent for one year compared with 35% receiving only professional treatments like cognitive behavioral therapy. AA is free.

AA is a peer-led support group. A common recommendation for newcomers seeking treatment is to go to “90 meetings in 90 days,” establish a routine, build a support network, and reinforce commitment to recovery. Individuals attending AA meetings weekly for six months had higher abstinence rates over a two-year follow-up period than those attending fewer meetings. Health providers report outstanding five-year outcomes using regimens combining behavioral-psychiatric treatment, medication. and AA.

90 AA meetings in 90 Days Plus Naltrexone

Because AUD medication adherence is poor, one alternative is to give long-acting injectable naltrexone once a month or to organize a supervised medication administration program for patients. However providers need to offer more than a pill or injection. Combining behavioral interventions, such as AA participation, and pharmacotherapy enhances treatment outcomes, as does supervised administration of acamprosate, naltrexone, or disulfiram.

Vivitrol, long-acting injectable naltrexone, blocks opioid receptors, reducing the rewarding effects of alcohol and diminishing cravings. Vivitrol with counseling can reduce heavy drinking days compared to placebo. We have often recommended 90 meetings in 90 days and Vivitrol injections after detoxification from alcohol and for another three months, followed by re-evaluation and usually continued treatments. Integrating supervised naltrexone, disulfiram, or acamprosate with AA or treatment support is often more effective than either approach alone.

Summary

There has not been a new treatment for AUD in 20 years. While disulfiram has been prescribed since 1951, it’s usually the shunned stepchild compared to “newer” naltrexone or acamprosate. However, experts have taken a new look at disulfiram, indicating it may be very effective in some patients with AUD looking to give up drinking totally. Rather than either/or, Naltrexone, disulfiram, acamprosate, and Injectable naltrexone are safe to use and effective against AUD but should be prescribed and supervised as part of a program with behavioral treatment and AA to maximize the likelihood of success.