02. Alcohol Use Disorder: Should Disulfiram Be First-Line?

Text version

Alcohol Use Disorder: Prevalence and Treatment Gap

Alcohol use disorder (AUD) is one of the most prevalent psychiatric conditions in the United States. An estimated 29 million US residents had AUD in 2023. Of these, only about 2% received pharmacological treatment for their AUD.

Clearly, medication is underutilized in the treatment of this chronic and sometimes life-threatening disorder.

FDA-Approved Medications for AUD

The Food and Drug Administration has approved three medications for AUD treatment:

• Disulfiram
• Acamprosate
• Naltrexone

Disulfiram, first approved in 1951, is used far less often than the other two. Only about 200,000 patients take disulfiram annually.

Disulfiram’s Poor Reputation

Disulfiram’s unpopularity stems from two main factors:

1. It can cause potentially life-threatening side effects when combined with alcohol.
2. It shows little to no benefit over placebo in randomized, double-blind, placebo-controlled clinical trials.

As a result, major clinical practice guidelines rate disulfiram as a second-line treatment option behind acamprosate and naltrexone.

Dr. Holt’s Argument for Disulfiram

Dr. Stephen Holt argues that disulfiram doesn’t deserve this bad reputation. He believes that with proper supervision and appropriate patient selection, disulfiram should be considered a first-line treatment for AUD.

Disulfiram as a Medication-Assisted Behavioral Therapy

Dr. Holt’s first point is that disulfiram acts as a medication-assisted behavioral therapy rather than a direct pharmacological intervention. Disulfiram interferes with the metabolism of alcohol, resulting in the buildup of a toxic metabolite.

When patients taking disulfiram consume alcohol, they experience almost immediate side effects like headache, nausea, vomiting, and flushing. The expectation of these uncomfortable effects reduces alcohol craving and strengthens patients’ confidence in avoiding drinking.

Limitations of Double-Blind Trials

Dr. Holt’s second point addresses the limitations of double-blind, placebo-controlled clinical trials in measuring disulfiram’s efficacy. For disulfiram to work, patients must know they’re taking it.

As evidence, Dr. Holt points out that meta-analyses including only randomized open-label clinical trials do find disulfiram more effective than placebo and sometimes even more effective than acamprosate or naltrexone.

Evidence vs. Preference: Rethinking Treatment Guidelines

Dr. Holt’s third point challenges the basis for downgrading disulfiram to second-line status in clinical practice guidelines. He argues that physicians should base their treatment preferences more on the strength of the clinical evidence than on patient preferences.

In the case of disulfiram, the evidence should come from randomized open-label controlled clinical trials. Only after this initial evidence-based recommendation, should the physician-patient discussion about treatment take into account patient preferences.

Patient Selection for Disulfiram

Dr. Holt acknowledges that not all patients are suitable for disulfiram treatment. Patients must:

• Agree to have a responsible adult ensure they take disulfiram as prescribed
• Take the medication daily as a pill to ensure that blood concentrations are consistently high enough to trigger uncomfortable side effects if alcohol is consumed

Patients at high risk for severe side effects should not take disulfiram, including those with:

• Liver cirrhosis
• Unstable cardiovascular disease
• Clinically significant cognitive impairment

Clinical Bottom Line

In conclusion, I believe Dr. Holt has made a convincing argument for upgrading disulfiram to a first-line treatment for AUD. I would consider disulfiram for patients whose treatment goal is complete abstinence and who meet the eligibility criteria.

Abstract

Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder

Holt, Stephen R. M.D., M.S.

Despite the prevalence of alcohol use disorder (AUD) in the United States, the armamentarium of FDA-approved medications available for AUD treatment is remarkably small. Disulfiram, 1 of only 3 approved medications, is consistently designated as a second-line option in national treatment guidelines, citing inconsistent evidence, lack of patient preference, and safety concerns. These concerns, however, stem from a misguided interpretation of the evidence that exclusively relies upon double-blind randomized controlled trials (RCT). When viewed instead as both a medication and a behavioral intervention, open-label RCTs become a more appropriate research method, yielding overwhelmingly favorable efficacy data for disulfiram, and supervised disulfiram, in particular. With these data in mind, supervised disulfiram should be redesignated as a first-line intervention in both treatment guideline creation and clinical pathway tools. The addiction medicine community can no longer afford to neglect this critical therapeutic resource.

Reference

Holt, S. M.D., M.S. (2024).

Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder

. 

Journal of Addiction Medicine 18

(6):p 614-616, 11/12 2024.