Two existing medications - one used for smoking cessation and the other for depression - appear to work effectively together in treating alcohol use disorder. The combination reduces alcohol cravings, lowers consumption, and may decrease the risk of nausea. These findings come from a new study led by the University of Gothenburg, Sweden.

Alcohol use disorder is a serious condition that can shorten the lives of those with severe forms of the disorder by 25 years or more. Yet, existing treatments are effective for only a small subset of patients.

The results are published in The Lancet Regional Health – Europe. The study was carried out in collaboration with researchers from Karolinska Institutet, Lund University, and Linköping University. It introduces a potential new treatment strategy: boosting dopamine levels in the brain.

The researchers based their approach on the hypothesis that a dopamine deficiency drives the craving for alcohol. They aimed to enhance dopamine signaling by combining varenicline, which stimulates dopamine release via nicotine receptors, with bupropion, which helps the brain maintain dopamine levels after release.

Reduced consumption in 13-week trial

A total of 384 individuals with moderate to severe alcohol use disorder took part in the 13-week study. Participants were randomly assigned to one of four groups, receiving either the combination treatment, one of the two drugs alone, or a placebo. Neither the participants nor the researchers knew who received what during the trial.

Results showed the greatest reduction in alcohol consumption among those who received the combination therapy. Varenicline alone also produced a measurable effect. The outcomes were assessed using both blood biomarkers (B-PEth, which reflects long-term alcohol intake) and self-reported data.

One of the researchers behind the study is Bo Söderpalm, professor of psychiatry at the Sahlgrenska Academy, University of Gothenburg, and senior physician at Sahlgrenska University Hospital:

“We observed approximately twice the effect compared to currently available medications, which is highly promising. However, additional studies are required before the combination treatment can be approved for alcohol use disorder,” says Bo Söderpalm.

Less nausea improves tolerability

An important secondary finding was that the combination treatment caused less nausea, which is a known side effect of varenicline. Among those who did experience nausea, symptoms lasted for a shorter period of time, similar to what was observed in the placebo group.

Andrea de Bejczy, PhD researcher affiliated with the Sahlgrenska Academy and resident physician at Sahlgrenska University Hospital, played a central role in conducting the study:

“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,” says Andrea de Bejczy.