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Major Mayo/Hazelden study may advance personalized medicine for alcohol use disorder

binge drinking
Photo by Adam Wilson on Unsplash
The study, which will eventually involve some 800 subjects gathered from the addiction-treatment programs at Hazelden Betty Ford and Mayo Clinic, is funded by a National Institutes of Health grant distributed by the National Institute on Alcohol Abuse and Alcoholism.
For a person with alcohol use disorder (AUD), cravings are an Achilles heel. The desire for alcohol can be so strong and persistent that it is impossible to ignore.

There is a drug, known as acamprosate, that has a low side-effect profile and has been shown to reduce or even completely eliminate cravings for alcohol, but it only works for about 10 percent of patients. A new large-scale study conducted by researchers at Mayo Clinic and Hazelden Betty Ford Foundation aims to identify biomarkers that would predict patient response to the drug. That way, doctors could prescribe the medication to the patients with the highest chance of positive response.

This approach of isolating biomarkers for positive response to specific medication is already being used with many kinds of medications, including psychiatric medication. This would be the first study that focuses on a medication designed to treat addiction.

The study, which will eventually involve some 800 subjects gathered from the addiction-treatment programs at Hazelden Betty Ford and Mayo Clinic, is funded by a National Institutes of Health grant distributed by the National Institute on Alcohol Abuse and Alcoholism.


Marvin Seppala M.D., Hazelden Betty Ford’s chief medical officer, explained that this research is particularly exciting because AUD directly impacts the lives of millions of people worldwide.

“Alcohol kills more people than all other drugs combined,” Seppala said. “Even in the midst of this opioid crisis, it is still the No. 1 reason people come to the Hazelden Betty Ford Foundation.”

Though the 10 percent success rate of acamprosate, which has been approved for the treatment of AUD and available in the United States since 2004, may seem low, Seppala argues that it still has the potential to help a large number of Americans.

Marvin Seppala
“Ten percent is a big number when you look at all the people in this country who have AUD,” he said. With this research, Seppala added: “We’re aiming to identify exactly who can be helped by this medication. Once we find that out, the doors will open for so many more people.”

Victor Karpyak M.D., a consultant in Mayo Clinic’s department of psychiatry and the study’s principal investigator, said that acamprosate’s success rate is similar to that of most psychiatric medications.

“Although the number seems to be indicative of limited chances for success,” Karpyak said, “it is pretty much standard for most of the medications used in psychiatric practice.”

In psychiatry, Karpyak explained, it often takes several tries to identify the correct mediation to treat individual patients. That is why identifying biomarkers for psychiatric medications has been so helpful for physicians and patients.

“It is an inherent problem for the practice of medicine and psychiatry to find a match between existing medication options and the unique needs of each patient,” Karpyak said. “This is why we are doing this study, to identify biological markers which could allow us to come up with these medical options. This will make a significant difference for patients and physicians.”

For some, promise of a cure

When acamprosate works, it can feel like nothing short of a miracle.

Seppala told the story of one patient — the first person he witnessed responding to the medication. Previously, he had prescribed acamprosate to patients without success, and when he tried it with this particular patient, a middle-aged woman, he had little reason to hold out hope for a positive response.

The patient’s struggle with AUD was long-lasting and resistant to treatment, Seppala reported. Her husband was a long-haul truck driver who was gone during the week and home on the weekends.

“She managed to stay sober during the week while her husband was gone,” Seppala said, “but when her husband came home, he liked to have a beer with his wife while the they watched TV.”

Victor Karpyak
Victor Karpyak
Though Seppala’s patient had ongoing cravings during the week, she usually stayed away from alcohol while her husband was away. “But she’d always relapse on the weekend,” Seppala said. “She just wanted to spend time with her husband. It was the psychological triggers of spending time with him that limited her ability to stay sober.” Seppala said his patient tried traditional 12-Step meetings, therapy and other treatment methods, but they all failed. Over and over again, she kept relapsing.

As a last-ditch effort, Seppala suggested the patient try acamprosate. She agreed. Within two weeks’ time, Seppala recalled, “She said her cravings just went away. It was amazing. With this medication, she was able to finally stay sober. She continued to go to her 12-Step meetings because she felt she got community and support there, but she said that her cravings just disappeared.”

Seppala was amazed by acamprosate’s impact. “When you see this medication work,” he said, “it’s just remarkable.”

Stories like this one make Seppala feel excited about the potential impact of this study. So many people struggle with the disease of alcoholism; if he could have the opportunity to identify the individuals with AUD who would be best helped by this particular medication, he could see more people achieve a life of sobriety.

“If you can clearly identify the people most likely to respond to this medication,” he said, “they will have a much better chance of staying sober.”


As it is now, Seppala said that he rarely prescribes acamprosate to his patients.

“It is hard to convince a patient to try a medication that only works 10 percent of the time,” he said. “A patient might ask me, ‘Doc, why would I take this? Ninety percent of people don’t respond.’”

Whenever a physician prescribes a medication, he explained, they weigh the risk to the patient vs. the benefit. “If you don’t know a medication will benefit your patient, you don’t really know anything,” Seppala said. “You are just saying, ‘This might work.’ That is an uncomfortable place to be as a doctor when you are trying to advise patients in the best possible treatment for their condition.”

Other medications to reduce cravings

There are other medications that can be used to reduce cravings for alcohol. Antabuse, was the first medication approved by the Food and Drug Administration for the treatment of AUD. When a person taking the medication drinks alcohol, it causes an extremely unpleasant reaction, which can include copious vomiting, sweating, headache, chest pain, blurred vision and even loss of consciousness.

While this sort of reaction can be enough to keep anyone away from ingesting alcohol, Seppala said, it can be so violent that it is frightening. “When you are vomiting with such a high reaction people really don’t like taking it. We don’t use it much anymore — adherence rates are really low.”

Naltrexone, a medication that is also used in the treatment of opioid use disorder (OUD), can be used in the to reduce alcohol cravings in the treatment of AUD.

“Naltrexone helps with OUD,” Seppala said. The success rate with this medication hovers around “20-25 percent” for people with AUD, he explained. When it is used for the treatment of OUD, the drug works as an opioid antagonist, blocking the the activation of opioid receptors, and preventing the drug from producing a high. “When Naltrexone is used for OUD, the success rate is higher,” Seppala said.

Seppala said that he is most likely to prescribe acamprosate to patients as a last-ditch medication. “You only end up using it when other things have failed.”

The medication has to be taken three times a day, which can reduce compliance, especially when patients understand that there is a 90 percent chance the it may not work for them.

But acamprosate also has many positive qualities. “This is a fairly innocuous mediation overall,” Seppala said. “There are no dangerous side effects associated with it. The risk profile is low.” Though it is covered by many insurance plans, it can be expensive, he added: “When that’s the case, it can be troublesome.”

Seppala can’t help but think back to his earlier patient who responded so positively to the medication. If he could identify patients who were likely to have a similar response, he’d be far more likely to prescribe acamprosate. This study will make that possible, he believes.

“This is something that has the potential to help so many people with AUD,” Seppala said. “We are on the cusp of a major medical advance.”

Study details

The study is scheduled to be completed in five years. To a layperson eager for answers, that could sound like a long time; researchers focused on gathering hundreds of subjects and identifying biomarkers have a different perspective.

The study period, Karpyak said, “is not that long of a time, honestly, because five years in the context of what we are working on is actually a short period of time. Many people want results now and don’t want to wait a couple of days or months, but there is so much to do — and we will be finding out so much in a relatively short period of time.”

Study participants, recruited from Hazelden Betty Ford and Mayo, will be randomized to receive either an active form of acamprosate or a placebo that “looks the same but doesn’t have active ingredients,” Karpyak said. “It will allow us to see whether biomarkers associated with positive or negative response are specific to medication or other qualities of particular individuals.”

By analyzing patient response to the medication, researchers hope to come up with a genetic signature, or a combination of biomarkers that would come together to form a pattern associated with either a positive or negative response to acamprosate, Karpyak said. “In this case, the response would be defined by sobriety, meaning no drinking during the period of the study, which is three months.”

While participating in the study, subjects will continue to get AUD treatment as usual, Seppala said. “They will get all of the treatments that we or Mayo provide in addition to the acamprosate or the placebo. They’ll get everything that any other patient would get.”

Researchers will analyze blood samples and reported results from study participants. When enough data is collected, they will be able to run comparisons that will result in the identification of biomarkers.

“Using artificial intelligence,” Seppala said, “a computer can identify who responds to the medication and who doesn’t. From that the computer will look at all these different biomarkers and find the things that are common to the responders versus the non-responders.”

The differential indicators may be small. “It might just be one enzyme or some breakdown product in the brain or the gut,” Seppala said. “Or it could be all based on genetics. There must be some genetic subtype of alcoholic that responds to this medication. We haven’t identified it yet, but we will find out.”

Once the biomarkers are identified, Karpyak explained, determining if the patient is a good match for acamprosate “may be rather quick, depending on what kind of markers we would have.” If it is a genetic biomarker, he theorized, many patients could have quick access to results: “We can use the genome data, which may already be available if a person has had their genome sequenced through something like 23 and Me or other companies that are offering this type of service. Or we may end up finding markers based on blood metabolites. Then we will simply have to take a blood sample.”

Hope for the future

Seppala said that this study may be just the beginning of a revolution in AUD treatment.

“This should really shift how we view the treatment of those with AUD,” he said. “Right now, most people with AUD don’t want to take mediations. We are only able to convince about a third of our patients to try a medication.”

That may be chalked up to a spotty success rate, but a clear indication of success would change the equation. “Right now we can’t tell them for certain if a medication it is going to work to treat their AUD,” Seppala said, “but if we could tell them, ‘This medication is right for you based on your blood test,’ I think it would engage more people in the use of the medication and get better outcomes.”

The partnership with Mayo gives the project a major boost, Seppala added. Richard Weinshilbaum M.D., co-director of the pharmacogenomics program at Mayo Clinic’s Center for Individualized Medicine, is also a collaborator on the project.

“The folks at Mayo have a huge genetics lab,” Seppala said. “They have already been doing this kind of research on medications starting with cancer agents and moving to antidepressants.”

Because AUD is a complex disease compared to other disorders like hypertension, Karpyak explained that project researchers hope to discover a response signature, that could advance understanding of alcohol addiction in general. “This is a secondary outcome,” he said, “but it is an important one. It may guide us in terms of developing new medications.”

It’s that hope for a treatment that inspires project participants, Seppala said. Physicians treating patients with AUD are looking forward to the day when the disorder can be approached in a way that is similar to the treatment of many cancers.

“The day will come when we can take a ‘personalized medicine’ approach and find the medication that is right for this person and not for that person,” Seppala said. “This will mean a significant change in how we treat AUD.”

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