Research Spotlight: Comparing the GI Side Effects of Four Medications for Alcohol Use Disorder

Wei Zhang, MD, PhD, a physician investigator in the Division of Gastroenterology at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School, is the senior author of a new research letter in Clinical Gastroenterology and Hepatology, Gastrointestinal and Liver Adverse Effects of Alcohol Use Disorder Medications: A Pharmacovigilance Analysis.

Summary:

Our study analyzed the gastrointestinal (GI) and liver side effects of four medications used to treat alcohol use disorder (AUD): disulfiram, acamprosate, oral naltrexone, and injectable naltrexone.

Using data from the FDA Adverse Event Reporting System, we found that injectable naltrexone had the fewest reported GI and liver-related side effects compared to the other drugs.

This is important because concerns about medication safety often prevent people with liver disease from starting treatment for AUD.

Our findings suggest that injectable naltrexone may be a safer option, potentially leading to better treatment adherence and improved health outcomes for patients.

Background

This study addresses an important challenge in treating alcohol use disorder (AUD), particularly in patients with liver disease.

While medications for AUD can reduce the risk of developing alcohol-associated liver disease (ALD), concerns about their safety, especially their impact on the liver, have led to hesitation in using them.

In the past, naltrexone was thought to cause liver toxicity, which discouraged its use in patients with ALD. However, more recent evidence suggests this risk may have been overstated.

Our goal was to analyze and compare the gastrointestinal (GI) and liver-related side effects of the four FDA-approved medications for AUD.

We used reports from the FDA Adverse Event Reporting System (FAERS) to evaluate the safety profiles of these drugs, with a focus on how they might affect patients with liver disease.

We pursued this research to help address a key clinical issue—how to provide safe, effective treatment for AUD in patients with or at risk for liver disease.

Our findings suggest that injectable naltrexone may be a safer option compared to other medications. This information could encourage broader use of injectable naltrexone, giving patients access to effective treatment while reducing concerns about liver-related side effects.

What are the Clinical Implications and Next Steps?

By showing that injectable naltrexone has fewer liver and gastrointestinal side effects compared to other AUD medications, our findings support its use as a safer treatment option.

This could encourage more clinicians to prescribe injectable naltrexone for patients with liver disease, who are often excluded from AUD treatment due to safety concerns.

Improved access to treatment could lead to better management of AUD in ALD patients and reduce the risk of liver disease progression.

The next steps include further research to confirm these findings in real-world clinical settings, especially for patients with advanced liver disease.

Prospective studies could provide stronger evidence to guide treatment decisions.

Additionally, educational efforts aimed at clinicians may be necessary to increase awareness about the safety of injectable naltrexone for this patient population.

Paper Cited:

Hwang, S. Y., Luther, J., & Zhang, W. (2024). Gastrointestinal and Liver Adverse Effects of Alcohol Use Disorder Medications: A Pharmacovigilance Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, S1542-3565(24)01134-0. Advance online publication. https://doi.org/10.1016/j.cgh.2024.12.009