Study Examines Novel Ways of Treating Alcohol Use Disorder

In our work with people diagnosed with substance use disorder (SUD) and alcohol use disorder (AUD), we take an evidence-based, integrated, whole-person, all-of-the-above approach to treatment and support. This means we meet each patient where they are, learn who they are and where they want to go, then create a treatment plan that helps them meet their goals, while accounting for their personal history and the various needs unique to their situation. We apply this approach to treating alcohol use disorder and other substance use disorders, as well.

In addition to therapy, counseling, peer support, community support, and lifestyle changes, one method we employ is called medication-assisted treatment (MAT). To learn more about MAT, please navigate to our medication-assisted treatment page.

Most people who engage in MAT therapy have a diagnosis for opioid use disorder (OUD). Evidence shows that MAT with medications for opioid use disorder (MOUD) yields the best results for people diagnosed with OUD – that’s why it’s considered the gold-standard treatment for OUD. To learn more about MAT for OUD, please visit the blog section of our website and read these two articles:

Medication-Assisted Treatment for Opioid Addiction

Methadone or Suboxone? If I have OUD, How Do I Decide?

While medications for opioid use disorder (MOUD) are relatively well-known because of the opioid overdose crisis, what many people don’t know is that in addition to treating OUD, there are also evidence-based medications for treating alcohol use disorder.

In this article, we’ll discuss those medications, thanks to a thorough meta-analysis published in May 2022 in the peer-reviewed journal Drugs. The meta-analysis – “Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder” – offers a comprehensive discussion of all the medications either already approved for treating AUD or currently in the research and review process for treating AUD and other substances.

Let’s get right to the discussion.

Medication for Treating Alcohol Use Disorder: An Overview

Since every person develops alcohol use disorder (AUD) in a way that’s unique to their personal history, and every case of AUD is different, it’s unrealistic to think we can find one medication that works for all people in all cases . That means there’s a need for the scientific community to there is a need to develop new approaches to AUD treatment – with a focus on medication/pharmacological treatments – in order to increase treatment participation and improve overall treatment effectiveness and success.

This article discusses the various pharmacotherapies – some old, some new, and some in development – currently available or nearly available for treating alcohol use disorder, including:

• Disulfiram
• Acamprosate
• Naltrexone
• Nalmefene
• Topiramate
• Gabapentin
• Varenicline
• Baclofen
• Sodium oxybate
• Aripiprazole
• Ondansetron
• Mifepristone
• Ibudilast
• Suvorexant
• Prazosin
• Doxazosin
• N-acetylcysteine
• GET73
• ASP8062
• ABT-436
• PF-5190457
• Cannabidiol

Before we dive into a review and discussion of these medications for treating alcohol use disorder, we’ll address alcohol use disorder itself. We’ll offer a simple definition of AUD and present the rates of AUD worldwide and in the United States. Then we’ll discuss the effectiveness of current methods for treating alcohol use disorder, relapse rates for people in treatment, and address the concept of recovery and what it means for people who seek treatment for AUD.

First, we’ll define AUD and present the most recent statistics available.

Alcohol Use Disorder: Facts and Figures

We’ll start this section with a simple definition of alcohol use disorder, extracted from the complete clinical definition in the Diagnostic and Statistical Manual of Mental Disorders, Volume 5 (DSM-5):

“Alcohol use disorder (AUD) is a chronic, relapsing condition characterized by an impaired ability to stop or control alcohol use despite clinically significant impairment, distress, or other adverse consequences.”

For more details on alcohol use disorder and the criteria clinicians use to diagnose AUD, please read our page here:

Alcohol Use Disorders

To learn more about AUD, its causes, and the various negative consequences associated with alcohol use disorder and substance use disorders, please read these articles on the blog section of our website:

Genetics and Alcohol Use Disorder: Can Genes Predict Who Will Develop Alcohol Use Disorder?

The Connection Between Suicide, Alcohol and Substance Use Disorders

Those resources contain reliable information on the topic at hand. Now let’s take a look at rates of AUD around the world. Here’s the latest data:

• AUD diagnosis worldwide:
  • 4 million people diagnosed with AUD
• Effect of AUD worldwide:
  • World Health Organization (WHO) data indicates AUD is responsible for:
    • A total of 5.9% of all deaths: 7.6% in men and 4.0% in women
    • An estimated 5.1% of global disease burden
  • The WHO estimates alcohol use and misuse contributes to worldwide rates of physical pathologies such as:
    • Cardiovascular disease
    • Cancer
    • Liver disease
    • Accidents and injuries
  • The WHO also estimates alcohol use and misuse contributes to worldwide rates of mental health disorders such as:
    • Major depressive disorder (MDD)
    • Bipolar disorder (BD)
    • Anxiety disorders
    • Other psychiatric disorders and conditions

Those figures are staggering: one hundred million people worldwide report a diagnosis of AUD, which contributes to increases in overall mortality, overall physical pathology, and overall mental health pathology.

The story is clear: AUD is a significant problem around the world.

Now let’s narrow the focus and look at rates of alcohol use, misuse, and disordered use in the United States. We retrieved the following data from the 2021 National Survey on Drug Use and Health (2021 NSDUH):

Alcohol Use in the U.S: Past Month, Heavy Drinking, Binge Drinking, and AUD Among Adults Age 12+

• Current use: 133.1 million
• Binge drinkers: 60.0 million (45.1%)
• Binge drinkers, by age group:
  • 18-25: 29.2% (9.8 million)
  • 26+: 22.4% (49.3 million)
  • 12-17: 3.8% (995,000)
• Binge drinking among underage people: 8.3% (3.2 million)
• Heavy alcohol use among underage people: 1.6% (613,000)
• Alcohol use disorder:
  • Overall: 10.6% (29.5 million)
  • Age 12-17: 3.4% (894,000)
  • Age 18-25: 15% (5.0 million)
  • Age 26+: 10.7% (23.6 million)

Now let’s look at the number of people diagnosed with AUD who received treatment for AUD.

AUD Treatment in 2021 Among People with AUD

• Overall: 4.6% (1.4 million)
• Age 12-17: 3.6% (32,000)
• Age 18-25: 2.7% (136,000)
• Age 26+: 5.0% (1.2 million)

Finally, let’s look at the number of people who used medication assisted treatment (MAT) for alcohol use disorder.

Medication-Assisted Treatment for Alcohol Use or Alcohol Use Disorder

• A total of 2.6 million people age 12+ received treatment for alcohol use, including people without a clinical AUD diagnosis
  • Among those, 15.1% (381,000) participated in MAT for AUD
• Among the 29.5 million people with a clinical AUD diagnosis:
  • Only 0.9% (265,000) participated in MAT for AUD

Before we go on to discuss what recovery is and review the various pharmacological options for AUD treatment, we should point out the key points in the data above. First, the rates of binge drinking – defined as consuming more than (5) drinks on one occasion for men, and (4) drinks on one occasion for women – in the U.S. are surprising, and present ample reason to be concerned that millions of people may escalate to disordered use. In addition, heavy drinking – defined as consuming more than (15) drinks a week for men, and (8) drinks a week for women – is also increasing, and presents ample reason for the same concern: heavy use increases risk of escalation to AUD.

While those points are relevant to this discussion and to our work supporting people with AUD, what we want to note is the enormous treatment gap, which is the difference between the number of people who need treatment for AUD and the number of people who receive treatment for AUD. The treatment gap is something we work every day to reduce.

Now let’s talk about and offer a definition of recovery from AUD.

Hint: it might not be exactly what most people think.

What is Recovery?

It’s important to understand that recovery means different things to different people. It’s also essential to understand this key point:

Every individual definition of recovery is valid for that individual.

What many people may not understand is that the generally accepted concept of recovery from AUD – complete abstinence from alcohol forever – is not the treatment or recovery goal for every person who seeks professional support for AUD. Experts estimate the 75 to 85 percent of people who seek total abstinence experience relapse at least once during their recovery journey, which means total abstinence is never easy in any circumstances. In addition, evidence from two clinical studies showed that only around 5 percent of patients with AUD – out of a total of 300 patients – placed total abstinence as their primary treatment goal.

This concept – recovery without total abstinence – is a component of an approach to the disordered use of alcohol and drugs known as harm reduction. A simple way to think about harm reduction is that the approach embraces any means available to reduce the negative consequences of substance misuse for individuals, families, and communities – including approaches that don’t prioritize total abstinence as the end-goal or criteria for being in recovery.

In 2007, the Hazelden Betty Ford Foundation defined recovery as:

“A voluntary maintained lifestyle characterized by sobriety, personal health, and citizenship.”

In 2012, the Substance Abuse and Mental Health Services Administration (SAMHSA) offered a more inclusive definition of recovery:

“A process of self-directed change through which individuals improve their health and wellness, live self-directed lives, and strive to reach their full potential.”

Then, the American Society of Addiction Medicine (ASAM) published this comprehensive definition, which includes and integrates the fundamental components of the definitions above:

“Recovery is a process of sustained action that addresses the biological, psychological, social, and spiritual disturbances inherent in addiction. Recovery aims to improve the quality of life by seeking balance and healing in all aspects of health and wellness, while addressing an individual’s consistent pursuit of abstinence, impairment in behavioral control, dealing with cravings, recognizing problems in one’s behavior and interpersonal relationships, and dealing more effectively with emotional responses.”

Now it’s time to review the various medications – i.e. the pharmacological treatment modalities – for alcohol use disorder, with the full awareness that for some patients, the goal of using these medications is total abstinence, while for others, the goal may be to reduce alcohol consumption enough to prevent the harm is causes in their lives.

Medications for AUD: What They Are, How They Work, And How Effective They Are

We’ll start with dedications approved to treat AUD by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA):

Disulfiram

Approved in 1951, this is the first FDA-approved medication for AUD. It works by preventing the metabolism of alcohol. If a person drinks after taking disulfiram, they may experience nausea, vomiting, sweating, flushing, and increased heart rate. While some patients achieve recovery with disulfiram, the side-effects mean many patient drop out of programs with disulfiram. It’s now recommended help maintain abstinence, rather than reduce drinking in general.

Acamprosate

This medication works as a partial agonist for NMDA receptors in the brain, which helps reduce cravings for alcohol and decreases the urge to use alcohol. Acamprosate does not ease withdrawal symptoms, but once an individual completes the withdrawal phase, evidence shows it can help reduce rates of relapse in people with AUD.

Naltrexone

This medication is most often used for patients with opioid use disorder (OUD). It binds to opioid receptors in the brain, and prevents the action of opioids and substances like alcohol on the endogenous opioid system. Evidence shows treatment with naltrexone can reduce alcohol seeking, reduce binge drinking, and reduce overall alcohol consumption in people with AUD.

Nalmefene

This medication is an opioid receptor antagonist and partial agonist. It’s FDA-approved in the U.S. to reverse opioid overdose, and approved by the EMA in France for treating AUD. Evidence shows treatment with nalmefene can reduce binge drinking and total alcohol consumption.

Medication approved to treat AUD in France:

Baclofen

This GABA receptor agonist can help people with AUD increase rates of abstinence, increase time to relapse, and reduce overall days of heavy drinking.

Medication approved to treat AUD in Italy and Austria:

Sodium oxybate

This medication regulates GABA receptor activity in the human brain. Evidence shows it can mitigate the symptoms of alcohol withdrawal and improve rates of abstinence to alcohol use.

The following dedications have been repurposed from other uses for AUD. Some have undergone preclinical trials in the rodent model, while others have undergone these preclinical trials and clinical trial in humans for AUD treatment:

Topiramate

This medication acts on the GABA system. Evidence shows it reduces alcohol intake the rodent model, and in clinical trials in humans, evidence shows it helps increase abstinence, reduces drinks per day, and reduces heavy drinking days.

Gabapentin

This medication modulates GABA activity. In the rodent model, this medication both reduce and increase alcohol intake. In humans, evidence shows can reduce alcohol withdrawal symptoms, increase time to relapse, and reduce heavy drinking days.

Varenicline

Varenicline is a nicotinic receptor agonist. In the rodent model, this medication reduced alcohol seeking, alcohol intake, and binge-like behavior. In humans, it can reduce heavy drinking days, with an increased effectiveness for people who smoke cigarettes.

Aripiprazole

This medication is a partial opioid receptor agonist. In rodents, it reduces alcohol consumption. In humans, evidence is mixed: it can reduce heavy drinking days in rates similar to naltrexone, and shows improved results for people with increased impulsivity.

Ondansetron

Evidence shows this mid-brain receptor agonist can reduce alcohol intake in the rodent model. In humans, evidence shows it can help reduce drinks per day in abstinent patients with early-onset AUD.

Mifepristone

Evidence shows this glucocorticoid receptor agonist can reduce alcohol seeking in the rodent model. In  humans, evidence shows this medication can reduce alcohol craving and overall alcohol consumption.

Ibudilast

This medication inhibits the action of brain areas related to alcohol consumptionm. In the rodent model, evidence shows it can reduce alcohol intake. In humans, evidence shows it can help reduce alcohol craving and reduce likelihood of heavy drinking.

Prazosin and Doxazosin

These medications are adrenergic receptor antagonists. In the rodent model, evidence shows these medications can reduce relapse-related behavior and alcohol intake. In humans, evidence shows these medications can reduce alcohol withdrawal symptoms, reduce cravings, and reduce overall alcohol consumption.

We’ll end this section with a list of new medications that have not been repurposed and are in development to treat AUD:

• N-acetylcysteine
• GET73
• ASP8062
• ABT-436
• PF-5190457
• Cannabidiol

Evidence in the rodent model shows that some of these medications have promise in reducing alcohol intake, some help reduce relapse-related behavior, and some can do both. However, among these medications, only N-acetylcysteine, ABT-436, and PF-5190457 have undergone clinical trials in humans, where the results – to date – have been relatively underwhelming and show only moderate promise for effective AUD treatment.

How This Information Helps

The impact of MAT on people with OUD is overwhelmingly positive. Many people consider MAT a lifesaving approach to OUD treatment – it’s that effective. That’s why scientists search for medication that can work for AUD: there’s a high likelihood that effective AUD medication can not only improve, but also save lives. The data in this article help remind our patients and families that we have currently have three medications – disulfiram, acamprosate, and naltrexone – that are effective treatments for AUD. However, while these medications are effective, scientists believe we can find medications that are as effective for AUD – with its associated 75-85 percent relapse rate – as the current selection of medications are for opioid use disorder (MOUD).

That’s the goal: find the gold-standard medication for AUD. We’re close, and have effective medications that are woefully underutilized. As the evidence we present above shows, less than one percent of people with AUD participate in MAT for AUD.

With advocacy and awareness efforts, we can change that. We can help more people reduce the harm caused by AUD, and people work towards total abstinence and sobriety, if those are their long-term goals for treatment.

We’ll continue our work in treatment, and the scientists will continue their work searching for new medications for AUD. When they find a new, safe, effective medication for AUD to complement those we already have, we promise to report about it here as soon as the information is available.