Off-label treatment for alcohol use disorder is linked to slower liver decline, study suggests

WASHINGTON — There are three FDA-approved drugs for treating alcohol use disorder. But a different medication, one frequently used off-label for the condition, could provide greater benefit to patients with alcohol-associated liver disease, a new study suggests. 

The data, presented this week as an abstract at Digestive Disease Week in D.C., suggest anti-seizure gabapentinoids might be a simple and effective treatment for slowing the progression of alcohol-associated liver disease. Nearly 30 million adults in the United States have alcohol use disorder, according to the 2022 National Survey on Drug Use and Health. 

The toll of alcohol-associated liver disease, including mortality, has been increasing for years, though exact estimates of ALD prevalence are hard to measure because many people go undiagnosed. Alcohol is the top reason people need a liver transplant in the U.S. As a result, researchers and biotech companies alike are trying to find ways to stop the liver inflammation and scarring that cause end-stage disease. 

Lead author Raj Shah, a fourth-year chief resident at the University of Central Florida and Orlando VA healthcare system, pulled VA data from 2002 to 2021 to conduct the research. He and his collaborators then matched 24,477 pairs of patients who had been diagnosed with alcohol use disorder and prescribed gabapentinoids or acamprosate.

Acamprosate, sold as a generic and brand name Campral, was approved by the FDA in 2004 for treating alcohol dependence, and works in part by reducing symptoms of withdrawal. Gabapentin gained first approval in 1993, and is used to treat nerve pain, partial seizures and fibromyalgia. Gabapentin is thought to work by soothing parts of the nervous system involved in seizures, pain, and more. 

The Florida researchers compared patients’ liver disease progression (defined as a combination of a bunch of diagnostic codes) in those taking either drug. People with liver failure or who’d received a liver transplant were excluded. They found that 15.8% of patients on acamprosate progressed to severe liver scarring in the form of compensated (asymptomatic) or decompensated cirrhosis, alcoholic hepatitis, alcohol-associated liver disease, or liver cancer, versus 13.4% of the gabapentinoid group. Acamprosate users also had slightly higher rates of decompensated and compensated cirrhosis than those on gabapentinoids.

And in veterans who had pre-existing liver disease, 30.4% of those on acamprosate got worse versus 25.8% of gabapentinoids users. The findings were presented as an abstract, and therefore have not been peer-reviewed or published in full yet.

The study did not measure changes in liver scarring because that information wasn’t regularly collected in the early 2000s, said Shah, who also works at HCA Florida Osceola Hospital. Since the study is retrospective, its findings are limited — it doesn’t prove that gabapentin alone slowed down progression of alcohol-associated liver disease. The researchers also didn’t check whether the recommended dosage of either drug was reached. Shah says higher-quality trials comparing acamprosate and gabapentin head-to-head are necessary to prove out what he found. 

Gabapentin, while commonly prescribed for various conditions, comes with its own risks. In 2019, the FDA warned that people with respiratory conditions or who also take nervous system-suppressing drugs (like opioid painkillers) could experience fatal breathing issues. Between 2012 and 2017, at least 12 people died from respiratory depression while taking gabapentinoids, the agency found. At high doses, the drug can also increase a person’s risk of falls, Shah said. 

And, notably, trials of gabapentin against placebo as a treatment for alcohol use disorder and withdrawal have had mixed results (an extended-release version failed to work better than placebo). 

But there are some practical reasons why gabapentinoids might work better than other drugs for some patients, Shah said. For one thing, treatment with acamprosate requires patients to take six pills per day. The other FDA-approved medications, naltrexone and disulfiram, also have shortcomings. With the latter, sold under brand name Antabuse, drinking alcohol while taking it can cause strong side effects. Naltrexone (brand name ReVia, Vivitrol, and Depade) is hard on the liver, and can’t be used once patients reach severe levels of disease.   

Gabapentinoids, because of their nervous system-cooling effect, could also help address root causes that are driving patients to drink (and leading to worsening liver disease), Shah said. About a quarter of the veterans he studied had made a visit to the VA pain clinic, and more than 90% had mental health visits. About half smoked or had another substance use disorder, he said. Some studies suggest gabapentin can help treat some anxiety disorders. 

“If we’re able to, with gabapentin, kill two birds with one stone — able to treat their pains as well as their alcohol use disorder — then it’s warranted, using gabapentin versus just using acamprosate,” he said. 

Researchers separated out a group of patients who took their medication for at least a full 120 days, to make sure the difference couldn’t be chalked up to one group being more adherent than the other. The researchers also took into account demographics, liver and kidney function, vital signs, health care use, medication use, recent visits to pain or mental health clinics, or comorbid conditions.