“Success” for people with alcohol-use disorder has traditionally been measured as total and complete abstinence. That’s the model that Alcoholics Anonymous uses and most people are familiar with. But a group of researchers believes that shifting the model — so that a reduction in the amount of drinking could also be considered a success — would encourage more people to seek treatment and give pharmaceutical companies an incentive to develop more drugs to treat alcohol-use disorder.
“It’s a new era of both meeting people where they’re at but also educating people about what the academics know about how the brain works, how it’s affected by alcohol and how that can be reversed by medication,” said Raymond Anton, M.D., Distinguished University Professor, Department of Psychiatry and Behavioral Sciences and Scientific Director of the Charleston Alcohol Research Center. He also serves as chairman of the Alcohol Clinical Trials Initiative (ACTIVE) workgroup under the American Society of Clinical Psychopharmacology. The group includes representatives from pharmaceutical companies, government regulatory and funding agencies and academic institutions. The ACTIVE group published a paper in JAMA Psychiatry on Wednesday, one of a series on this topic.
The paper outlines the group’s look back at three large multi-site clinical trials testing drugs on alcohol-use disorder. The Food and Drug Administration currently considers abstinence and “no heavy drinking days” as primary outcome measures for such drug trials. A heavy drinking day is four or more drinks for women and five or more drinks for men.
The ACTIVE group reanalyzed the trial data, using the World Health Organization’s risk drinking levels for alcohol. The levels are divided into very high risk, high risk, medium risk and low risk, according to the grams of pure ethanol (number of drinks) consumed each day. The group then looked at how many trial participants were able to move down one or two risk levels — for example, moving from the very-high-risk category to the medium-risk category would be considered a two-level reduction.
What they found was that more people had been able to reduce their drinking than had been able to remain completely abstinent or have zero heavy drinking days. In fact, abstinence had the lowest achievement rate for all three trials. The greatest number of patients succeeded in reducing their WHO risk by one level, and the next most successful group reduced it by two levels.
That might not look like success according to the traditional goal of complete sobriety — and it wasn’t considered a success at the time of the clinical trials — but reducing alcohol consumption can have a huge effect on a person’s health and well-being, according to Anton. In others papers published by the ACTIVE group, a one or two-level reduction in WHO risk drinking level caused an improvement in a number of health and social variables. Offering a reduction in drinking as a goal of medication treatment likely would encourage more people with alcohol problems to consider treatment.
“If they have the choice between drinking moderately or abstinence, almost everybody is going to choose drinking moderately. Our society is built around that. Being abstinent is a very hard thing to do, both because the brain has been changed by chronic alcohol use leading to dependence, and also the social stigma around complete abstinence,” Anton said.
He’s not dissuading people from seeking abstinence if that works for them, he stressed. Instead, he thinks that people should look at alcohol use disorder the same way they look at diabetes or high blood pressure – as chronic conditions that can be managed, but not cured, with medication and behavioral counseling and lifestyle changes.
“If they have the choice between drinking moderately or abstinence, almost everybody is going to choose drinking moderately. Our society is built around that. Being abstinent is a very hard thing to do, both because the brain has been changed by chronic alcohol use leading to dependence, and also the social stigma around complete abstinence.”
Dr. Raymond Anton
There’s a vast gap in what scientists have learned about how alcohol affects the brain, leading to dependence and addiction, and what most people know about alcohol, he said.
“They don’t know there’s really a well-established science around studying alcoholism, what is now officially called alcohol-use disorder, with basic science and good clinical trial methodologies. It’s changing what many people think of as a social or a moral condition into more of a scientific or medical discussion. A good part of the people in the country still don’t understand that, I think,” he said.
If the FDA were to loosen its guidelines to include a reduction in “WHO risk drinking levels” as a desirable outcome for clinical trials — as is currently done in Europe — drug companies would probably be more willing to develop medication to treat alcohol-use disorder, Anton said. There are only three FDA-approved medications for alcohol-use disorder, the last of which was approved in 2006. The first one, Antabuse, was approved almost 60 years ago. The abstinence guideline by itself is simply too high a bar for medications development, Anton said, plus the drug companies’ research shows that potential customers aren’t as interested in taking medicine if the only option is to commit to lifelong abstinence. Right now, only 20 percent of those who could benefit from alcohol treatment actually get it, and only 4 percent actually receive one of the medications shown to help reduce drinking and promote abstinence.
“The information published in this paper, and others by this group, could be ushering in a new era of medication development for alcohol-use disorder and possibly attract more people to treatment who would not have considered it previously,” he said. That would be a positive outcome for individuals and their families with alcohol problems, serve society well and likely lower costs of health care nationally.