Disulfiram, often known by the brand name Antabuse, was approved by the FDA in 1951 as a first-line treatment for patients with alcohol use disorder (AUD). Most doctors today do not prescribe it because it is often assumed that patient compliance is poor: if the patient taking the drug each alcohol causes profuse vomiting.
However, Stephen R. Holt, MD, director of Yale University’s Addiction Recovery Clinic, disagrees. “Recently,” he points out, “there was a shortage of disulfiram. I was very surprised to find that patients spent countless hours searching and searching for disulfiram in Canada, Europe or elsewhere, and continued to take their medication despite repeated obstacles.”
Disulfiram is safe, effective and lifesaving for patients with AUD who don’t want to drink 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 lifesaving, reversing what seemed to be untreatable AUD.
Another look at the oldest medicine: Disulfiram
Disulfiram was the first drug approved to treat addiction. It blocks the metabolism of alcohol and causes severe vomiting each alcohol is consumed. Reactions include flushing, nausea, vomiting, and cardiac and respiratory symptoms. A person’s fear of the aversive effects of the disulfiram-alcohol interaction may be a deterrent for some patients. Disulfiram is considered a second-line option by most physicians, with naltrexone being the most commonly prescribed and naltrexone and acamprosate serving as the first-line options.
30 years after the approval of Naltrexone
Naltrexone is an opioid receptor antagonist that was approved by the FDA in 1995 for the treatment of alcohol dependence as an oral preparation and, in 2006, as a long-acting injectable agent. Naltrexone blocks the rewarding effects of alcohol, a hypothesis supported by numerous preclinical and clinical studies. This means that naltrexone blocks the rush of opioids or alcohol, preventing intoxication with one daily pill. Because many patients did not take their naltrexone pill as prescribed, injectable naltrexone was developed.
Patients report that naltrexone takes most of the pleasure out of alcohol, preventing binge drinking and reducing drinking. When the goal is drinking fewer Rather than quitting altogether, naltrexone certainly helps individuals regain control by making alcohol less appealing. Naltrexone is metabolized in the liver and is contraindicated in patients with acute hepatitis and liver failure.
Acamprosate (calcium homotaurine)
The newest treatment for AUD, acamprosate (Campral), was developed in France. The FDA approved the drug 21 years ago, in 2004, for maintaining abstinence in detoxified alcoholics. Acamprosate restores the glutamate-related brain systems that are abnormal in patients with AUD, especially during acute and prolonged withdrawal.
Acamprosate helps restore the neuronal balance disrupted by chronic alcohol use. Like naltrexone, when taken it works to reduce drinking and alcohol cravings and to reduce the damage caused by drinking. It is not metabolized by the liver, but is excreted mainly by the kidneys. Its use is contraindicated in patients with severe renal impairment.
The debate: Antabuse or Naltrexone
There has been definitive research on the benefits of medications for AUD, but which treatment is better and for whom? The official of the American Society of Addiction Medicine Journal of Addiction Medicine contained an article by Dr. Holt in the November/December 2024 issue. He recommended rejecting the idea that acamprosate or naltrexone should be a first-line treatment; instead, he suggests using disulfiram as a first-line treatment.
Alcoholism essential reading
Holt states that disulfiram is a supervised drug viable and effective first-line treatment for many patients with AUD. Supervised administration ensures compliance, which is crucial for the efficacy of disulfiram. Holt also emphasizes patient selection: ideal candidates are abstinence-motivated, have a supportive environment, and can commit to regular monitoring. He addresses concerns about hepatotoxicity, noting that the risks are manageable with appropriate patient selection and monitoring.
In contrast, Sarah Axelrath, an addiction specialist trained at Massachusetts General Hospital (MGH) and currently with the Colorado Coalition for the Homeless in Denver, argues that disulfiram should not be a first-line treatment for AUD. She recognizes that disulfiram can be effective for patients who are highly motivated to abstain, who have no medical or psychiatric contraindications, and who have strong family support. But she recommends other FDA-approved medications as first-line options, reserving disulfiram for rare cases where the potential benefits outweigh the risks.
Other medications are sometimes used off-label for AUDS
Although disulfiram, naltrexone, and acamprosate are the only medications approved by the FDA for AUD, other medications are sometimes prescribed off-label. For example, the epilepsy drug topiramate or semaglutide, the active ingredient in Ozempic and Wegovy, can help people drink less alcohol. Glucagon-like peptide-1 (GLP-1) drugs such as Ozemmpic are often prescribed for the treatment of diabetes and weight loss, which can give patients an incentive to take the drug as prescribed. More research is needed to compare GLP-1 medications with medications approved by the FDA for alcohol use disorders.
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 for people with AUD. AA meetings are widely available throughout the U.S., are free, and the program provides role models and sponsors to help others 24 hours a day. However, not everyone likes AA, and there are significant differences between meetings. However, AA works.
Cochrane review co-author Dr. John Kelly of Harvard’s MGH says their review shows that AA helps people shift their social networks from heavy drinkers to people in recovery. That’s what professional therapy tries to do, he notes, but AA does it in a more accessible and obviously cheaper way. For example, 42% of AA participants were completely abstinent for a year, while 35% only received professional treatments such as cognitive behavioral therapy. AA is free.
AA is a peer-led support group. A common recommendation for newcomers seeking treatment is to attend “90 Meetings in 90 Days,” establish a routine, build a support network, and strengthen commitment to recovery. Individuals who attended weekly AA meetings for six months had higher abstinence rates over a two-year follow-up period than those who attended fewer meetings. Healthcare providers report excellent five-year results using regimens that combine behavioral psychiatric treatment and medication. and A.A.
90 AA Meetings in 90 Days Plus Naltrexone
Because AUD treatment compliance is poor, an alternative is to administer long-acting injectable naltrexone once a month or to organize a controlled medication administration program for patients. But providers must offer more than a pill or injection. Combining behavioral interventions, such as participation in AA, and pharmacotherapy improves treatment outcomes, as does the controlled administration of acamprosate, naltrexone, or disulfiram.
Vivitrol, a long-acting injectable naltrexone, blocks opioid receptors, reducing the rewarding effects of alcohol and decreasing appetite. Vivitrol may reduce days of heavy drinking with counseling compared to placebo. We have often recommended 90 meetings in 90 days and Vivitrol injections after alcohol detox and 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 hasn’t been a new treatment for AUD in 20 years. Although disulfiram has been prescribed since 1951, it is usually the shunned stepchild compared to the ‘newer’ naltrexone or acamprosate. However, experts have taken a new look at disulfiram, indicating that it may be very effective in some patients with AUD who want to stop drinking altogether. Rather than either/or, naltrexone, disulfiram, acamprosate, and injectable naltrexone are safe to use and effective against AUD, but should be prescribed and monitored as part of a behavioral treatment and AA program to maximize the chance of success.
