Aligning genomic data and clinical health records identifies potential medications for treating alcohol use disorder

A novel approach has identified drugs in current use that could be repurposed for treating alcohol use disorder (AUD). In 2023, 28 million US adults had experienced AUD in the past year. But only three medications are approved by the FDA to treat the condition. Those drugs have uneven effectiveness, and health care providers’ lack of familiarity with them contributes to low use.

The cost of developing a new drug is $1–3 billion, but repurposing other medications with known safety profiles—a route that historically relied on clinical observation and chance discoveries—would be dramatically less expensive. The increasing availability of large databanks facilitates computational approaches that can efficiently screen for promising medication uses.

For the study, in Alcohol: Clinical & Experimental Research, investigators identified 327 alcohol-related genes. They screened for medications known to interact with those genes, finding 195 drugs that together targeted 52 genes.

The drugs were filtered for safety, relevance, and data availability, yielding a shortlist of 26. Working with electronic health records from the Department of Veterans Affairs (VA), the scientists identified patients who had been prescribed one or more of the 26 drugs between 2008 and 2023 and who had been assessed for alcohol use.

As a test case, the investigators focused on baclofen, used to treat muscle spasticity. Baclofen has been investigated for AUD efficacy with inconclusive results.

The scientists analyzed a cohort of 22,295 VA patients who had taken baclofen and matched patients who had not. Using advanced statistical techniques to ensure the two groups were similar on a wide range of sociodemographic and clinical characteristics, they then compared how each group’s self-reported alcohol use changed over time.

Alcohol use decreased in both groups, modestly more so among those who had been treated with baclofen. The reduced drinking associated with baclofen was more pronounced among patients with current AUD and those who’d reported hazardous drinking at baseline.

The analysis demonstrates an innovative approach to evaluating drugs for repurposing as AUD treatments, which may have potential for other neuropsychiatric conditions.

The findings included several genes linked to reduced drinking in animal studies, and all but one of the medications recommended in VA practice guidelines for treating AUD. Larger trials of baclofen in moderating drinking are needed, particularly among those with hazardous levels of alcohol use.