Do we have a game-changer for treating alcohol abuse? Several medications, when combined with therapy and support, are enabling some patients to cut back on alcohol intake or have fewer heavy drinking days. Even established alcohol treatment centers are now using these drugs to help patients achieve or maintain sobriety while law enforcement agencies are using the medicines with DUI (driving under the influence) offenders to help them reach abstinence or at least cut back on their drinking.
A Drug Therapy Story
By the time Patricia Sams appeared before a Missouri drug court for drunken driving in the spring of 2010, alcohol was ruling her life. Unemployed and barely able to function, Sams, who is now 48, was drinking a fifth of whiskey a day (approximately 26 ounces) and sometimes more. Living in a rented room in Crane, Mo., she kept a bucket beside her bed.
Sams — a drinker since she was 11 — was pulled over for her first drunken driving arrest when she was 28. More arrests followed, and she spent 44 months in either jail or prison. After a December 2009 arrest, Sams completed a 28-day detox program the following April. The drug court judge then offered her an opportunity to try something new: monthly injections of a drug that might curb her powerful craving for alcohol.
Three days after her first injection, Sams says she finally felt free of her cravings, and today, despite a family history of alcoholism, she continues to be alcohol-free. The drug she took for eight months is Vivitrol, a once-a-month injectable form of naltrexone, approved by the Food and Drug Administration (FDA) in 2006 to help treat alcohol abuse. While the drug does not work for everyone, many addiction specialists say it addresses the compliance problems that are still common with the older version of the drug, a pill, on which Vivitrol is based. The naltrexone pill has to be taken daily.
The Role of Drug Therapy
Alcohol abuse or alcohol dependency, known in medical terms as alcohol use disorder (AUD), is what happens when a person — probably due to both genetic and environmental factors — is no longer capable of controlling the use of alcohol. What causes the addiction is often difficult to determine, although family history is widely thought to play a role in at least half of all cases.
For years, drug treatment of alcohol addiction got short shrift from physicians and addiction specialists in favor of behavioral intervention services, counseling and social support groups like Alcoholics Anonymous (AA), which were widely considered to be more effective. But starting with the introduction of naltrexone in 1994, the number of drugs for treating alcohol abuse began to expand. Today’s medicines are more effective and often make it easier for drinkers to remain sober and comply with a treatment regimen.
The newer drugs are not a cure for alcohol abuse, and so far, it’s not clear how long they remain effective. For many people, the drugs are most effective for reducing the intense craving that typically comes with alcohol addiction. More often than not, the drugs are prescribed only in conjunction with counseling and support services in people who are currently abstinent. The premise is that alcohol abuse is a condition that typically involves both physical and psychological components, which means that treating it effectively usually hinges on lifestyle changes.
Still, some physicians think drug therapy deserves far more attention than it’s gotten so far. In one study, published in the Journal of the American Medical Association, researchers at the University of North Carolina, Chapel Hill, looked at 120 previous studies, and, in an accompanying abstract, concluded that anti-alcohol medications are “considerably underused.”
Results of a study published in BMC Medicine agree. Researchers examined 89 randomized, controlled trials that enrolled nearly 11,200 people and involved oral naltrexone; studies involving opioid or ex-opioid users were excluded. Most of the trials studied alcohol-use disorder, though others included smoking, psychiatric disorders and impulse control disorders.
Side effects associated with naltrexone include nausea, vomiting, abdominal pain, decreased appetite and dizziness. The drug used to have a “black box” warning about the risk for drug-induced liver damage, but this has since been removed from its labeling.
While there was no increased risk of serious adverse events for naltrexone compared to placebo, a second analysis showed six marginally significant adverse events for naltrexone, though they were deemed mildly severe.
“Though naltrexone is licensed for the treatment of alcohol addiction, it remains underutilized,” lead author Monica Bolton, MD, of the University of Manchester (UK), said in a statement. “It is cost-effective and could reduce deaths.”
At Hazelden Betty Ford Foundation, a nonprofit Minnesota-based institution with 17 treatment centers in 9 states, Marvin D. Seppala, MD, the chief medical officer, estimates that about a third of the center’s patients now leave with some type of medication that might reduce their craving for alcohol, and therefore, the likelihood of a relapse.
At Hazelden and Tarzana Treatment Centers — a Southern California-based organization with 10 offices — the current drug of choice is Vivitrol. “It’s been quite effective for us,” said Ken Bachrach, PhD, the clinical director at Tarzana. “We don’t believe that medications like Vivitrol are the answer to alcohol misuse, but we see it becoming another option. For some people, the effect is dramatic, and for some people, less so. In general, it seems to cut the urge to drink in half, which means that people can focus on their recovery, they can pay attention in a group setting, and they can walk down the aisle of a store and not have as strong an urge [to drink].”
At Families Matter, a treatment center in Villas, N.J., alcohol abusers who come in for help now typically receive six monthly injections of Vivitrol, along with what director Patricia Campbell describes as “intensive” group counseling, as well as individual counseling. Her center was part of a pilot program administered by the New Jersey Division of Mental Health and Addiction Services to give Vivitrol to DUI offenders, or those found driving under the influence of alcohol.
According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), in 2018, 14.4 million Americans aged 18 and older, or 5.8% of this age group, had AUD. An estimated 401,000 youths aged 12 to 17, or 1.6% of this age group, had AUD. About 7.9% of adults and 5% of youths with AUD received treatment during this time period. Nearly a third of adults have had it at some point in their lives.
Do I Have AUD?
The current Diagnostic and Statistical Manual of Mental Disorders (DSM), a guide produced by the American Psychiatric Association to define and help clinicians identify mental disorders, classifies the severity of AUD as mild, moderate or severe based on the number of positive answers to a questionnaire on symptoms. Questions ask about symptoms over the past year and range from whether you’ve had times when you drank more than you intended to drink, to whether you experienced withdrawal symptoms as the effects of alcohol wore off.
If you answer Yes to having two out of the 11 symptoms listed, you are diagnosed with AUD. The severity of AUD is defined as mild if you have two to three symptoms, moderate if you have four to five symptoms and six or more means you have severe AUD.
AUD versus Alcohol Abuse
Previous versions of the DSM used the terms “abuse” and “dependence” to describe a person’s severity of AUD. Abuse, also referred to as alcohol misuse, meant that people usually have some control over their drinking, they drink in a way that often harms their health, personal relationships, driving ability and ability to work. Alcohol dependence referred to alcohol abuse that has progressed to the point where someone is not only unable to stop drinking but has also developed a physical tolerance to high levels of alcohol. People who are considered alcohol-dependent would now be classified as having severe AUD, typically suffering from withdrawal symptoms such as anxiety, trembling, sweating, nausea, insomnia and depression when they stop drinking.
It’s been estimated that only 20% to 30% of alcoholics ever receive any treatment for their condition, and less than 10% receive any of the medications available for treating alcohol dependence. Meanwhile, the social and health costs of alcohol use disorders continue to grow. According to a study released by the Centers for Disease Control and Prevention, one in 10 deaths among working-age adults between the ages of 20 and 64 is due to excessive alcohol use. Alcohol use disorders have been shown to increase a person’s risk of developing a number of medical problems, like breast cancer, liver disease and heart disease.
Which Drug Treatments Are Available?
So far, the FDA has approved only three drugs for use in treating alcohol use disorders: disulfiram (Antabuse), naltrexone (Revia pill, Vivitrol injection) and acamprosate (Campral). (See 5 Meds Help Curb Alcohol Abuse .)
None of the drugs address all aspects of alcohol abuse or prove effective with all patients. Some are better at reducing the craving for alcohol, while others are more effective for reducing the number of heavy drinking days or lessening the chance that someone who is abstinent will drink again. There is no clear and convincing evidence that the drugs work well in combination therapy.
For example, at Hazelden, Dr. Seppala has found that Vivitrol helps only about 30% of those who take it. “These drugs are the first to be based on understanding the neurochemistry of alcoholism, so in a way they’re like the first antibiotics,” he said. “I’m hoping we can eventually get better predictors of who should take them.”
Modern efforts to treat alcohol abuse with medication began in the late 1800s when alcoholics and their physicians began turning to a grab bag of often widely hyped elixirs such as arsenic, opium, cocaine and strychnine. In 1951, the FDA approved the use of disulfiram, an “avoidance” drug that makes drinkers sick if they swallow alcohol while taking the drug. Because of the drug’s toxic side effects, it never really took off.
Its use was soon eclipsed by interest in behavioral interventions, including cognitive-behavioral therapy (CBT), and the 12-step motivational programs offered by groups such as AA.
Disulfiram is thought of as a second-line option, meaning acamprosate and naltrexone would be considered first. Disulfiram should only be used in patients with sufficient physician supervision. It works by causing often intense side effects such as nausea, vomiting and palpitations if a user consumes even a small amount of alcohol; the effects may last a few hours, or in some cases, up to two weeks. While serious side effects are far less common, they do occur: liver failure, severe hepatitis, and even death have been seen when the dosage of the drug was not carefully monitored. Disulfiram should not be taken by anyone who has psychosis, severe heart disease, or a blocked artery to the heart. For someone who is not drinking, the drug’s most frequent side effect is drowsiness.
Disulfiram is now typically prescribed only when the patient has stopped drinking for 12 hours, and it seems to work best in people who are already committed to abstinence. According to Dr. Seppala, Hazelden rarely prescribes the drug anymore, but it has been helpful in two types of patients: “really impulsive” drinkers who have an inability to stay sober over time, and people who are new to recovery, but who are suddenly faced with a significant life event — such as a wedding — where the goal is to simply get through the party alcohol-free.
Naltrexone is the drug most commonly prescribed in the United States for treating alcohol abuse. It was approved by the FDA in 1994 for use as a once-a-day pill (Revia). In 2006 it was approved for injection once a month (Vivitrol). Some addiction treatment centers, however, are also prescribing naltrexone implants, which are not FDA approved. Naltrexone implants are inserted under the skin, usually in the lower abdomen, causing the drug to be slowly released over a 10- to 12-week period.
Unlike disulfiram, naltrexone does not cause unpleasant side effects if a patient consumes alcohol. Instead, it works with the brain’s chemistry to lower the positive feedback of drinking — it reduces the pleasant “buzz” that comes with the first drink or two. It can be effective for reducing the frequency and the severity of relapses that may occur during alcohol abstinence, as well as the risk of heavy drinking, which is now defined as binge drinking on five or more days in the past month. (Binge drinking is four or more drinks on one occasion in the past month for women and five or more drinks for men.)
Side effects can still be an issue with naltrexone. While the most common side effects are diarrhea and stomach cramping, the drug has been shown to cause liver damage if taken in large doses. Because naltrexone should be avoided by anyone who already has liver disease, it has limited usefulness for many people who already have a serious drinking problem. Moreover, compliance is a big problem with the pill form of naltrexone: some data indicating that more than 80% of oral naltrexone users stop taking their pills within six months of initiating use. Patients find it too difficult to take a pill daily and find that their craving for alcohol, while diminished, is still there.
The Sinclair Method
FDA approved indications for naltrexone require drinkers to abstain from drinking in an outpatient setting before beginning the drug. Some addiction specialists espouse another controversial approach: the so-called Sinclair method. Based on the work of the late American psychologist John David Sinclair, this approach is founded on the assumption that naltrexone works only if someone continues drinking. In his initial studies (using lab rats), and in his later interviews, Sinclair has said that the drug is 78% effective in either reducing drinking or producing complete abstinence after it’s been taken for three months or more. Criticisms of the method include its requirement that people continue to drink in order for it to work.
Compliance is also a problem with acamprosate (Campral), which is taken in pill form three times a day. Unlike naltrexone, acamprosate doesn’t interfere with the “high” that comes with alcohol use. Instead, the goal is no drinking — it is believed to somehow stabilize brain chemistry to lessen the chance that someone will drink again. The drug is believed to promote abstinence by alleviating the sleeping problems, sweating and anxiety that accompany abstinence.
Acamprosate has not been shown to work in people who haven’t stopped drinking, and its use must be monitored when a patient is also taking street drugs or certain prescription drugs such as antidepressants. While the drug is usually well-tolerated, it can cause diarrhea, headache, flatulence and nausea. Less often, the drug causes serious side effects such as depression and suicidal thoughts. It should not be used by anyone with kidney problems.
Still, the research shows that drugs like acamprosate and naltrexone may be effective for some people in treating aspects of alcohol abuse. In their review, the University of North Carolina researchers found that acamprosate and the pill form of naltrexone seem to be most effective for helping reduce alcohol use.
Alkermes, Vivitrol’s manufacturer, says that its drug is aimed at people who can abstain from alcohol in an outpatient setting and who are also undergoing counseling. In a study published in the Journal of the American Medical Association in 2005, shortly before Vivitrol was approved by the FDA, the drug — depending on the dose — was found to reduce heavy drinking episodes by 17% to 25%.
Because Vivitrol is injected in the buttocks with a special needle, its use requires regular medical visits. Its most common side effects are nausea, headache, vomiting and reactions such as tenderness and swelling at the injection site. Dosage changes can sometimes help alleviate certain symptoms, like nausea. More serious side effects are rare, but they include severe injection-site reactions that may lead to tissue death, a type of severe pneumonia, depression, suicidal thoughts and a greater risk of overdosing (perhaps fatally) if someone is also taking opiates such as heroin or prescription pain medicines.
Like the pill form of naltrexone, Vivitrol can cause liver damage or hepatitis. It should not be used by anyone who has acute hepatitis or liver failure, or who is either dependent on opiates, taking prescription painkillers, taking cough, cold or diarrhea medicines that contain opiates, or who is going through active opiate withdrawal.
Despite its limitations, Vivitrol has attracted attention from a number of publicly funded addiction treatment programs, including in Los Angeles County, where the drug has been shown to help alcohol abusers stay in treatment longer. Alkermes estimates that the drug is now in use in criminal justice programs in 43 states, including state, county and drug court initiatives. While each injection can cost $1,000 or more, the drug is now covered by more than 90 percent of insurance plans. Oral naltrexone is covered by every state Medicaid plan but not all cover Vivitrol. Meanwhile, for private payers, Alkermes has set up a $500 per injection co-pay program for patients with commercial health insurance or who are paying cash and taking the drug for an FDA-approved use. In 2010, Vivitrol was approved for treating opiate addiction as well.
Which Drug is Best?
Addiction specialists are continuing to analyze the data for clues as to why some anti-alcohol medications, such as Vivitrol, work better in certain people. “Anecdotally, my experience with it has been that it’s more effective for people who have a long family history of alcohol issues,” said Ken Bachrach at Tarzana Treatment Centers. “But then I also find that these people have higher cravings to begin with.”
The researchers at the University of North Carolina looked to see how many patients, on average, needed to be treated with a particular medication before a single patient saw some benefit. They found that, in order to prevent a return to any drinking, 12 patients needed to be treated with acamprosate and 20 for oral naltrexone. Naltrexone — in pill form — also helped reduce the risk of a return to heavy drinking. By contrast, Vivitrol, the injectable form of naltrexone, was associated only with reducing the number of heavy drinking days, and not with abstinence.
How AA Compares
A high-quality study reviewing 27 studies comparing Alcoholics Anonymous to other methods made headlines when the results favored AA. The authors found that AA participation led to higher rates of “continuous abstinence over months and years when compared to other active treatment approaches such as cognitive-behavioral therapy. The evidence suggests that 42% of participants participating in AA would remain completely abstinent one year later, compared to 35% of participants receiving other treatments including CBT.”
There are some flaws in the study, but the success rate is compelling and the cost is right – it’s free and available in every country, every day.
Dozens of smartphone apps have been developed to help people reduce or abstain from alcohol. However, an evaluation of 40 free or low-cost apps aimed at alcohol recovery found that few integrated evidence-based interventions, such as CBT or medication, and some even promoted drinking. The researchers determined that the use of these apps in real-world clinical settings is limited. They also expressed concern that they could possibly exacerbate relapse risk or worsen alcohol use. The researchers suggest that apps that are only available through a clinical office, such as the e-Recovery Connections App, could be assessed for individual use through online app stores.
New Drugs on the Horizon
Assessment for medication use has become routine in determining the best treatment plan for people with AUD. In their practice manual on addressing alcohol use, the American Academy of Family Physicians notes that substance use disorder counseling combined with medication is the most effective treatment for patients with AUD. Research has shown that certain medications that have not been FDA approved for AUD treatment are proving helpful.
Topamax and Neurontin
Researchers have reported encouraging results with some anticonvulsants, particularly topiramate (Topamax) and gabapentin (Neurontin). The APA practice guidelines for AUD treatment recommend topiramate or gabapentin as second-line treatment after the approved AUD drugs. Topiramate may be useful in individuals who are still actively drinking, even though that medication can produce troublesome side effects — such as memory and cognitive problems — if its use isn’t monitored properly. (See MedShadow’s Gabapentin’s Side Effect Risks)
In a 2020 study in JAMA Internal Medicine, researchers tested gabapentin, which is widely used to treat epilepsy and also neuropathic pain, for its benefits in treating AUD in people who experience alcohol withdrawal symptoms. Results showed that compared to placebo, gabapentin was useful in reducing drinking and promoting abstinence, especially in people with more severe alcohol withdrawal symptoms. The researchers suggest that improvements in sleep and possibly mood may have contributed to gabapentin’s usefulness.
The antinausea drug ondansetron (Zofran) has helped reduce drinking and cravings and increase abstinence in patients with early-onset AUD (those aged 25 or younger). Some research has narrowed down potential candidates for ondansetron benefits to those with a specific genotype. The researchers propose a pharmacogenetic approach — determining drug response in relation to specific genes — using ondansetron to treat severe drinking and improve abstinence in people with AUD. Common side effects of ondansetron include headache, constipation and fatigue.
In an NIAAA supported study, the antismoking drug varenicline (Chantix) lowered the weekly percentage of heavy drinking days, the number of drinks per drinking day and alcohol craving compared to a placebo in people with AUD. The researchers suggest that when patients come in to see their healthcare provider for smoking cessation, it could be an opportunity for clinicians to identify patients at risk for AUD. They note that more research is needed to confirm these apparent benefits and identify those who could benefit most from varenicline. Common side effects of varenicline include nausea, abnormal dreams and constipation.
In 2013 the drug nalmefene (Selincro) was approved for use in the European Union for people with AUD. The drug, which is similar to naltrexone, is to be taken as needed when patients feel they are at high risk of drinking. Although pre-approval trials showed a reduction in the number of heavy drinking days, a subsequent review of clinical trials for nalmefene found that none of the trials provided adequate evidence that the drug reduced alcohol consumption in people with AUD. The researchers reported in PLOS Medicine that the studies were flawed and did not establish the value of nalmefene for AUD treatment. In fact, when the researchers did their own analysis of the trial data, using proper procedures, they concluded that alcohol consumption outcomes did not differ between the nalmefene and placebo groups.
A follow-up analysis in the journal Addiction reviewed clinical trials and approval-related documents pertaining to nalmefene and reported that “important weaknesses in nalmefene trial registration, design, analysis and reporting hamper efforts to understand if and how it can contribute to treating alcohol problems in general practice or elsewhere.”
Nonetheless, medications along with psychosocial intervention are now considered the cornerstone of AUD treatment. Despite the promise of drug therapy, some former alcohol abusers emphasize that there is far more to staying sober, particularly after a medication regimen ends. Patricia Sams, for example, experienced a year of sometimes intense withdrawal symptoms after she finished 8 months of Vivitrol injections. During that time, Sams often found it difficult to focus, write steadily, and taste and smell food.
Sams is now helping to run a faith-based recovery center in Branson, Mo. She continues to seek counseling — including at AA meetings — when she needs help herself. “I’m free of the cravings, but once in a while my brain tells me that a drink would be nice,” she said. “Alcohol is all around us, but I’m very, very aware of it.”
This feature is an update of an article published September 4, 2015.