A medication known as spironolactone may aid the treatment of alcohol use disorder, according to a new study published in Molecular Psychiatry. The research was led by scientists at the U.S. National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
“Alcohol use disorder (AUD) affects 14.5 million people in the United States alone, yet less than 10% of people with AUD receive any treatment, despite the availability of behavioral treatments and three medications approved for AUD,” explained study author Lorenzo Leggio, a physician-scientist and senior investigator at NIAAA and NIDA, who also serves as the NIDA deputy scientific director and acting clinical director.
“As such, one of our critical missions is to develop new safe and effective treatments for AUD. Our previous preclinical research suggests that the mineralocorticoid receptor (MR) may play a role in alcohol consumption and craving. Furthermore, we previously found that aldosterone, an endogenous hormone that acts on the MR, is correlated with alcohol consumption and craving in patients with AUD.”
“Based on these observations, we have hypothesized that spironolactone, a medication used in clinical practice for hypertension and heart disease, may reduce alcohol consumption, given that it is an MR blocker,” Leggio said. “Therefore, our hypothesis is that spironolactone (and/or other medications acting on the MR) represents a new potential medication for AUD, hence allowing us to increase the armamentarium of options to treat patients with AUD.”
In experiments conducted in mouse and rat models of excessive alcohol drinking, the researchers found that spironolactone reduced the intake of sweetened and unsweetened alcohol solutions without affecting food or water intake. It did so in a dose-dependent manner, meaning that greater doses of spironolactone resulted in greater reductions in alcohol consumption.
Leggio and his colleagues also analyzed data from more than 45,000 individuals from the U.S. Veterans Affairs healthcare system. Alcohol consumption was measured by the Alcohol Use Disorders Identification Test-Consumption, a common screening instrument. They found that people who were prescribed spironolactone tended to reduce their alcohol consumption more than matched controls who were not prescribed spironolactone. Consistent with the rodent studies, they found a dose-dependent effect of spironolactone in humans.
“We showed, through experiments performed in mice and rats, that spironolactone decreases alcohol consumption,” Leggio told PsyPost. “Moreover, in a complementary analysis of health records of a large sample of people from the U.S. Veterans Affairs healthcare system, we found that individuals who had been prescribed spironolactone (for reasons such as heart problems or high blood pressure) were more likely to self-report reduced alcohol consumption.”
“We were happily surprised that the effects of spironolactone on alcohol consumption were observed in a consistent matter across mice, rats, and humans, and across different animal procedures and different clinical database. This level of consistency and replication gives us assurance that spironolactone and/or other medications acting on MR are worth further investigations, as part of our broader efforts of developing new treatments for AUD.”
“Of note, the latter results found in humans are consistent with another recent study we conducted in a different healthcare system database, in collaboration with Kaiser Permanente North Carolina,” Leggio added.
The results from the current study are particularly relevant, the researchers said, because they were found among U.S. veterans, who have an increased likelihood of developing AUD. Importantly, the largest effects were observed among those who reported hazardous/heavy episodic alcohol consumption before starting spironolactone treatment.
However, Leggio noted that “it is also important to keep in mind that these findings are preliminary, and we cannot conclude that spironolactone is an effective treatment for AUD.”
“What we can say for sure is that spironolactone is a promising new medication, hence the importance of continuing this line of research,” he explained. “The ultimate goal is that, similar to other chronic medical diseases, practicing clinicians will have a larger menu of treatment options to choose from, when they treat a patient with AUD.”
Additional research is necessary before spironolactone can be approved as a treatment for AUD.
“This work should be seen as preliminary and a first step of a more complex pathway that is needed to understand whether this medication may be effective in patients with AUD,” Leggio explained. “Chiefly, this work argues for conducting future randomized, placebo-controlled studies of spironolactone in people with AUD. Furthermore, we need additional work to understand the mechanisms related to the role of the MR in AUD and how spironolactone reduces alcohol drinking.”
“It is important to see this work as part of our larger mission of developing new treatments, including new medications, for patients with AUD. In fact, at present, only three medications are approved in the U.S. to treat AUD. Not all people with AUD will respond to available medications, but for a subset of individuals, they can be an important tool in their treatment. Scientists are working to develop a larger menu of treatments that could be tailored to individual needs.”
“Future work will also need to understand who the patients are, if any, that may respond to spironolactone, among those people with AUD,” Leggio said. “In fact, AUD is a complex heterogenous disorder, and ‘one size does not fit all,’ so our efforts in developing new medications for AUD need to include research aimed at identifying precision medicine approaches.”
The study, “Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies“, was authored by Mehdi Farokhnia, Christopher T. Rentsch, Vicky Chuong, M. Adrienne McGinn, Sophie K. Elvig, Eliza A. Douglass, Luis A. Gonzalez, Jenna E. Sanfilippo, Renata C. N. Marchette, Brendan J. Tunstall, David A. Fiellin, George F. Koob, Amy C. Justice, Lorenzo Leggio, and Leandro F. Vendruscolo.
