A groundbreaking study from the University of Gothenburg has demonstrated that combining two existing medications—varenicline and bupropion—can effectively treat alcohol use disorder by targeting dopamine deficiency in the brain. The research, published in The Lancet Regional Health - Europe, offers new hope for patients with a condition that can reduce life expectancy by 25 years or more.
The 13-week randomized, double-blind, placebo-controlled trial involved 384 individuals aged 25 to 70 years with moderate to severe alcohol use disorder. Participants were randomly assigned to receive either the combination treatment, one of the two drugs alone, or a placebo, with neither participants nor researchers knowing which treatment was administered during the trial.
Targeting Dopamine Deficiency
The treatment strategy is based on the hypothesis that dopamine deficiency drives alcohol cravings. Varenicline, originally developed for smoking cessation, stimulates dopamine release through nicotine receptors, while bupropion, an antidepressant, helps the brain maintain dopamine levels after release.
"We observed approximately twice the effect compared to currently available medications, which is highly promising," said Bo Söderpalm, professor of psychiatry at the Sahlgrenska Academy, University of Gothenburg, and senior physician at Sahlgrenska University Hospital. "However, additional studies are required before the combination treatment can be approved for alcohol use disorder."
Superior Efficacy and Tolerability
Results showed the greatest reduction in alcohol consumption among participants who received the combination therapy, with varenicline alone also producing measurable effects. The outcomes were assessed using both blood biomarkers (B-PEth, which reflects long-term alcohol intake) and self-reported data.
While the combination therapy was not proven to be more effective than varenicline alone, it demonstrated significantly improved tolerability. The combination treatment caused less nausea—a well-known troublesome side effect of varenicline—and among those who did experience nausea, symptoms lasted for shorter periods, similar to what was observed in the placebo group.
Clinical Implications
Andrea de Bejczy, PhD researcher at the Sahlgrenska Academy and resident physician at Sahlgrenska University Hospital, who played a central role in conducting the study, emphasized the importance of improved tolerability: "Nausea is a well-known and troublesome side effect of treatment with varenicline. It was surprising but very encouraging to see that nausea decreased when bupropion was added. The fact that the combination treatment is more tolerable for patients increases the chances that they will complete the full course of treatment."
The study provides pharmacological support for the dopamine deficiency hypothesis of alcohol use disorder and suggests that the varenicline-bupropion combination represents a well-tolerated, safe, and effective treatment option. This research was conducted in collaboration with scientists from Karolinska Institutet, Lund University, and Linköping University.
Current treatments for alcohol use disorder are effective for only a limited number of patients, making this potential breakthrough particularly significant for addressing the global burden of alcohol use disorder on healthcare systems and affected individuals.
