1.1.1. Treatments for Alcohol Use Disorder

Treatments for AUD continue to evolve as research on the effectiveness of various treatments is published and include a range of medications and behavioral approaches. Treatment may be delivered via intensive outpatient programs using group or individual counseling, addiction treatment centers, or general outpatient care.

The goals of treatment can range from abstinence to reducing alcohol use or harms related to alcohol use. Although abstinence has traditionally been cited as a predominant goal in much of the treatment literature, awareness has grown over the past 15 to 20 years that outcomes related to reduced alcohol consumption are clinically meaningful and important to patients. Some studies indicate that less than 10 percent of those with AUD are able to achieve long periods of reduced alcohol consumption.^23–27 As a result, research has used a broader array of outcomes to measure the effectiveness of treatment, which can be subsumed under the concept of tertiary prevention.²⁸ They include number of drinking or nondrinking days or heavy drinking episodes, physical health, healthcare costs, and psychosocial functioning. Research using non-abstinent outcomes provides evidence for the effectiveness of treatment for AUD. Miller et al.²⁹ analyzed seven large multisite trials. They found that whereas, in aggregate, about 25 percent of individuals maintained sobriety over 1 year, the remaining non-abstinent individuals showed substantial decreases in drinking days (from 63% pretreatment to 25% post-treatment) and a mean 57 percent decrease in drinks per drinking day. Thus, even in the presence of small gains in abstinence there can be reductions in alcohol use that may be meaningful to patients and potentially affect health and other outcomes.

Treatment outcomes can be affected by many factors, including but not limited to the following: (1) AUD severity; (2) co-occurring conditions, including physical and mental health disorders that make treatment more challenging; (3) type of treatment, which can include multiple psychosocial interventions and several pharmacotherapies; (4) pathway to treatment, ranging from voluntary care seeking to legally mandated treatment; (5) patient desires and preferences; (6) stigma; and (7) lack of access to treatment. This complexity contributes to variance in treatment outcomes and makes it difficult to identify a single best treatment across all patients.

1.1.2. Pharmacological Interventions for Alcohol Use Disorder

This review focuses on the effectiveness of pharmacotherapy for AUD in the outpatient setting, including for the reduction of alcohol consumption as well as for achieving abstinence. Current use of pharmacotherapy is low, despite evidence of effectiveness for some medications. Medications for AUD may hold a Food and Drug Administration (FDA) indication for AUD or may be FDA approved for other indications and used off-label to treat AUD. This review covers the four medications with FDA indications for AUD and several other medications that have been studied and are used off-label in the United States.

From the 1950s until the early 1990s, AUD pharmacotherapy consisted only of disulfiram, which produces significant physical symptoms, such as nausea, emesis, and tachycardia, within 12 hours of alcohol consumption. Anticipatory fear of this response acts as a deterrent to consuming alcohol. Its effectiveness requires a high degree of patient motivation and adherence, thereby limiting its overall usefulness for many patients. Since the 1990s, two oral medications—naltrexone and acamprosate—and one long-acting intramuscular formulation of naltrexone have been approved by FDA for AUD. These medications were originally approved for people with alcohol dependence, generally after withdrawing from alcohol and together with psychological intervention.² Table 2 describes the medications available in the United States that are FDA approved for treatment of AUD, their mechanism of action, and dosing. A small group of additional medications are used off-label and have been studied for AUD treatment with some positive results. Table 3 describes the medications commonly used (off-label) for AUD that are included in this review.

Table 2

FDA-approved medications for treating adults with AUD.

Table 3

Medications commonly used off-label in the United States for adults with AUD.

1.1.3. Existing Guidance and Evidence Reviews

In 2011, the United Kingdom’s National Institute for Clinical Excellence released clinical guidelines on the identification and treatment of people with alcohol dependence and harmful alcohol use.² The guidelines, which focused on AUD treatment more broadly, include the following recommendations: (1) after a successful detoxification for people with moderate or severe alcohol dependence, to consider offering acamprosate or oral naltrexone in combination with an individual psychological intervention (cognitive behavioral therapies, behavioral therapies, or social network and environment-based therapies) focused specifically on unhealthy alcohol use; (2) to consider offering disulfiram in combination with a psychological intervention to service users who have a goal of abstinence but for whom acamprosate and oral naltrexone are not suitable or who prefer disulfiram and understand the relative risks of taking the drug; and (3) to have specialist and competent staff administer pharmacological interventions.

In 2014, the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program published a systematic review of pharmacologic treatment for AUD, which is the basis for this updated review.³⁵ The review included data from 135 studies, reported in 167 papers. Both acamprosate and naltrexone demonstrated effectiveness, with the number needed to treat (NNT) to prevent one person from returning to any drinking of 12 to 20, respectively. NNT for preventing one person from returning to heavy drinking was 20 for oral naltrexone at 50 mg per day. Injectable naltrexone was not associated with a benefit for return to any or heavy drinking, but there was a reduction in heavy drinking days, although the strength of the evidence was low. Since acamprosate did not show a benefit for the outcome of heavy drinking, no NNT was calculated for that outcome specifically. For disulfiram, there was weak evidence suggesting a benefit in some patients with excellent adherence, based on a subgroup analysis in one trial.

That review also examined a number of medications used off-label that are available in the United States and found moderate evidence at the time supporting the efficacy of topiramate. There was insufficient direct evidence to support benefits of pharmacologic treatment for improving health outcomes, rather than alcohol use outcomes.

The American Psychiatric Association (APA) recommends naltrexone or acamprosate as first-line therapy for patients with moderate to severe AUD.³⁶ Disulfiram, topiramate, and gabapentin may be second-line options depending on the patient’s goals, comorbidities, and lack of response or tolerance to first-line medications. The APA recommends against the use of antidepressants or benzodiazepines for treating AUD and against pharmacological treatment during pregnancy or breastfeeding except in certain circumstances. Naltrexone may also be used to treat a patient with AUD and a co-occurring opioid use disorder if the patient wishes to abstain from opioid use and can do so for 10 days before initiating naltrexone treatment.

The Department of Veterans Affairs and Department of Defense updated guideline³⁷ includes “strong” recommendations for oral naltrexone or topiramate and “weak” recommendations for acamprosate and disulfiram as first-line AUD pharmacotherapy for patients with moderate to severe AUD. These should be offered in combination with addiction-focused counseling.