Medications To Help Stop Drinking – The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, integrates the previous categories of alcohol abuse and alcohol dependence into the diagnosis of alcohol use disorder (AUD); Table 1 shows the complete criteria.

The National Institutes of Health estimated that AUD affected 9% of adult men and 5% of adult women in the United States in 2013, and many more adults and adolescents who used high-risk alcohol.

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There is inconsistent evidence to support the use of disulfiram (Antabuse) to reduce alcohol intake in patients with alcohol use disorder.

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A problematic pattern of alcohol use that results in clinically significant impairment or distress, as manifested by at least two of the following occurring within a 12-month period:

3. Much time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.

5. Repeated use of alcohol resulting in failure to fulfill major roles at work, school or home.

6. Continued use of alcohol despite persistent or periodic social or interpersonal problems caused or exacerbated by the effects of alcohol.

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9. Alcohol use continues despite knowledge of a persistent or recurrent physical or mental problem likely to be caused or exacerbated by alcohol.

B. Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms.

In early remission: Having previously met full criteria for an alcohol use disorder, none of the criteria for an alcohol use disorder have been met for at least 3 months but less than 12 months (with the exception of criterion A4, “Craving or strong desire or urge to use of alcohol” can be fulfilled).

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In sustained remission: Having previously met full criteria for an alcohol use disorder, none of the criteria for an alcohol use disorder have been met at any time during a period of 12 months or longer (with the exception of Criterion A4, “Craving or strong desire or urge to using alcohol” can be fulfilled).

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In a controlled environment: This additional specification is used if the individual is in an environment where access to alcohol is restricted.

The US Preventive Services Task Force (USPSTF) recommends screening adults for alcohol abuse and providing brief behavioral counseling to individuals who engage in risky or hazardous alcohol-related behaviors to reduce alcohol abuse.

Although the CAGE questionnaire is familiar to clinicians, its accuracy varies in ambulatory settings and is not recommended by the USPSTF. Individuals engaged in at-risk drinking should be counseled to reduce alcohol use, and patients diagnosed with AUD should be offered treatment such as brief behavioral interventions, support programs such as Alcoholics Anonymous, individual and group therapy, and medication. A study of more than 43,000 American adults found that only 24% of those with AUD received treatment.

Possible reasons for low treatment rates include social stigma of AUD, lack of understanding of AUD as a treatable condition, and lack of knowledge of pharmacotherapy and other treatment options for this disorder. Patients with AUD are at risk for alcohol withdrawal and may require medical treatment for withdrawal before starting treatment.

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“In the past year, how many times have you had five (for men) or four (for women and all adults over 65) or more drinks per day?”

The Substance Abuse and Mental Health Services Administration/National Institute on Alcohol Abuse and Alcoholism Consensus recommends pharmacotherapy along with behavioral interventions for AUD.

It is difficult to assess the benefit of medication because most studies assess outcomes such as drinks per day and days of drinking over a period of time, not abstinence and complications of alcohol abuse (eg, mortality, cirrhosis, alcohol-related arrests, job loss). Most studies of medication for AUD also include counseling, so it is difficult to assess the effects of medication without counseling.

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The Department of Veterans Affairs recommends considering naltrexone (Revia, Vivitrol) and/or acamprosate (Campral) for AUD treatment, along with counseling.

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The UK National Institute for Health and Care Excellence recommends considering acamprosate or naltrexone for the treatment of AUD, with disulfiram (Antabuse) as a second-line drug.

The Substance Abuse and Mental Health Services Administration/National Institute on Alcohol Abuse and Alcoholism Consensus provides a guide to the use of acamprosate, disulfiram, and naltrexone.

No drugs are approved for the treatment of AUD in adolescents younger than 18 years; therefore, these patients should be referred for subspecialty treatment. None of the drugs used to treat AUD have been proven completely safe during pregnancy or breastfeeding, so they should be used with caution in women of childbearing age.

An Agency for Healthcare Research and Quality (AHRK) review of 135 studies of pharmacologic treatment of AUD in the outpatient setting found moderate evidence to support the use of naltrexone and acamprosate, and insufficient evidence to support the use of disulfiram. The review also concluded that evidence is lacking for most other drugs, including those for off-label use and those undergoing trials. However, there is some evidence for topiramate (Topamax) and valproic acid (Depakene).

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Acamprosate. This drug appears to be most effective in maintaining abstinence in patients who do not currently drink alcohol.

It is safe in patients with impaired liver function, but should be avoided in patients with severe renal dysfunction. A systematic review of 27 studies, including 7,519 patients using acamprosate, showed a number needed to treat (NNT) of 12 to prevent relapse to any drinking.

A Cochrane review of 24 trials including 6,915 patients concluded that acamprosate reduced alcohol consumption compared with placebo (NNT = 9).

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One randomized trial showed no difference between acamprosate and placebo, although outcomes improved significantly in both groups. This may be because enrolled patients were highly motivated to reduce alcohol use, increasing the likelihood of success with any treatment.

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Disulfiram. There are limited trials supporting the effectiveness of disulfiram. It does not reduce the desire for alcohol, but it causes unpleasant symptoms when alcohol is taken into the body because it inhibits aldehyde dehydrogenase and alcohol metabolism. Compliance is a major limitation, and disulfiram is more effective when taken under supervision. One trial randomized 243 patients to naltrexone, acamprosate, or disulfiram with supervision for 12 weeks and found that patients taking disulfiram had fewer heavy drinking days, lower weekly consumption, and longer periods of abstinence compared with the other drugs.

However, a 2014 meta-analysis of 22 randomized trials found that in open-label studies, disulfiram was more effective than naltrexone, acamprosate, and no disulfiram, but blinded studies showed no benefit for disulfiram.

Naltrexone. Naltrexone, an opioid antagonist, reduces alcohol consumption in patients with AUD and is more successful in those who are abstinent before starting the drug.

The opioid receptor system mediates the pleasurable effects of alcohol. Alcohol ingestion stimulates endogenous opioid release and increases dopamine transmission. Naltrexone blocks these effects, reducing euphoria and cravings.

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A Cochrane review that included 50 randomized trials and 7,793 patients found that oral naltrexone reduced heavy drinking (NNT = 10) and slightly reduced daily alcohol consumption (NNT = 25). The number of days of heavy drinking and the amount of alcohol consumed also decreased. Injectable naltrexone did not reduce heavy alcohol consumption, but the sample size was small.

A subsequent systematic review of 53 randomized trials, including 9,140 patients, found that oral naltrexone increased abstinence rates (NNT = 20) and decreased binge drinking (NNT = 12). There was no difference between naltrexone and acamprosate. Injectable naltrexone has not shown benefit.

A randomized trial of 627 veterans with AUD who received injectable naltrexone or placebo found that 380 mg of naltrexone given intramuscularly reduced heavy drinking days over six months but did not increase abstinence rates.

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Another meta-analysis found no difference in heavy drinking between acamprosate and naltrexone; however, he favored acamprosate for withdrawal and naltrexone for craving.

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Studies of combination therapy with acamprosate and naltrexone have produced mixed results. The COMBINE study did not show that combination therapy was more effective than either drug alone.

Another study found that relapse rates were lower with combination therapy compared with placebo or acamprosate alone, but not compared with naltrexone alone.

It is unclear whether and when combination therapy should be used, although it may be reasonable to consider it if monotherapy fails. Opioid antagonists can also be helpful when used as needed during high-risk situations, such as social events or weekends.

Naltrexone is well tolerated and non-habit forming. Because it is metabolized in the liver, hepatotoxicity is possible, although rare. Patients with AUD may have liver dysfunction; therefore caution is required. Naltrexone can cause severe opioid withdrawal in opiate-dependent patients, so these agents should not be used together, and opioids should not be used for at least seven days before starting naltrexone.

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Anticonvulsants. There are several anticonvulsants that may help patients with AUD to reduce alcohol consumption, but data are limited. A Cochrane review of 25 trials including 2,641 patients showed that those taking anticonvulsants (ie, topiramate, gabapentin [Neurontin], valproate, levetiracetam [Keppra], oxcarbazepine [Trileptal], zonisamide [Zoneepranin], [Tgaba] [Lirica]), or tiagabine [Gabitril]) consumed 1.5 fewer drinks per day than those taking placebo. There was no difference in abstinence rates compared with naltrexone, but anticonvulsants were associated with fewer heavy drinking days and a longer time to

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