Alcohol and Alcohol Use Disorder _ _____________________________________________________________
Several medications are available to help treat alcohol use disorder [324; 325]. Some are used for detoxification and others are used to prevent relapse. Research has shown that medications are most effective when used in conjunction with other therapies. Disulfiram Disulfiram, commonly known as Antabuse, was the first drug to be made available for the treatment of alcohol use disorder. It was approved for treatment of alcohol use disorder by the FDA in 1951 and has been used safely and effectively for more than half a century. It works by blocking an enzyme, aldehyde dehydrogenase, that helps metabolize alcohol. Taking even one drink while on disulfiram causes the alcohol at the acetaldehyde stage to accumulate in the blood. This produces nausea, vomiting, sweating, and even difficulty breathing. More alcohol in the patient’s system produces more severe reactions (e.g., respiratory depression, cardiovascular collapse, unconsciousness, convulsions, death) [325; 326]. Patients must also be mindful of consuming even minute amounts of alcohol in foods, over-the-counter medications, mouthwash, and even topical lotions. Disulfiram can be effective for people who have completed alcohol withdrawal, are committed to staying sober, and are willing to take the medication under the supervision of a family member or treatment program [325]. Due to more modern and improved medication modalities, many clinicians prescribe disulfiram as a last resort intervention. Although widely used, it is less clearly supported by clinical trial evidence [327; 328; 329]. The recommended dose for disulfiram is 250 mg/day, which can be increased to 500 mg based upon whether a patient experiences the disulfiram-ethanol reaction [330]. Doses may need to be reduced in patients older than 60 years of age [325]. Labeling for disulfiram includes several precautions regarding drug-drug interactions; therefore, caution should be used when prescribing it to older adults at risk for polypharmacy [325]. Due to the physiologic changes that occur with use, use of disulfiram is not recommended in patients with diabetes, cardiovascular or cerebrovascular disease, or kidney or liver failure. It also is contraindicated in the presence of psychoses and pregnancy and in those with high levels of impulsivity and suicidality [325]. Naltrexone Naltrexone (ReVia) is an opioid antagonist that interferes with the rewarding or pleasurable effects of alcohol and reduces alcohol craving [331; 332; 333]. The exact mechanisms by which naltrexone induces the reduction in alcohol consumption observed in patients with alcohol use disorder is not entirely understood, but preclinical data suggest involvement of the endogenous opioid system [325]. Naltrexone has been shown to reduce alcohol relapses, decrease the likelihood that a slip becomes a relapse, and decrease the total amount of drinking [325]. The FDA approved the use of oral naltrexone in alcohol use disorder in December 1994 [325; 333]. In 2006, the FDA approved an extended-release injectable formulation, which
is indicated for use only in patients who can refrain from drinking for several days prior to beginning treatment [325]. In 2010, the FDA approved the injectable naltrexone for the prevention of relapse to opioid dependence following opioid detoxification [325]. Naltrexone, which has long been used to treat heroin addicts, was not known as a treatment that could reduce alcohol relapse until the 1980s. In 1980, researchers reported reductions in monkey ethanol self-administration when they were pretreated with naltrexone [334]. By 1992, researchers reported a six-week, double-blind placebo- controlled outpatient naltrexone trial with 70 individuals with alcohol use disorder. They found that the naltrexone-treated patients had a lower relapse rate, fewer drinking episodes, longer time to relapse, and reduced tendency for a slip to become a relapse [335]. These and other data suggested that endogenous opioids were important in alcohol reinforcement. Also in 1992, researchers compared naltrexone with placebo and found that naltrexone-treated patients had lower rates of relapse to heavy drinking, consumed fewer drinks per drinking- day, and had lower dropout rates than placebo-treated patients with alcohol use disorder [336]. These results have since been supported by other studies [337]. Research suggests that naltrexone may be most effective for individuals with alcohol use disorder and a family history of alcohol use disorder [338]. However, one study found no significant effects for naltrexone in individuals with a family history of alcoholism on percentage of days abstinent, drinks per drinking day, and percentage of heavy drinking days [339]. Another study investigated pretreatment social network variables as potential moderators of naltrexone’s treatment effects [340]. The study sample included 1,197 participants from the COMBINE study, the largest pharmacotherapy trial conducted for alcoholism in the United States. In treatment conditions involving combined CBT and medical management, the effects of naltrexone on heavy drinking were significantly greater for individuals with frequent drinkers in their social network and greater frequency of contact with those drinkers, indicating patterns of environmental exposure to alcohol [40; 341]. In an attempt to replicate and extend the findings of the COMBINE study, researchers conducted a secondary analysis of a 12-week randomized clinical trial of daily or targeted naltrexone among problem drinkers, with a focus on those who received a daily dose of either naltrexone or placebo [342]. Four reward/relief phenotypes were identified: low reward/low relief; low reward/high relief; high reward/ low relief; and high reward/high relief. When compared with the placebo group, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer drinks per drinking day and a lower proportion of heavy drinking days [342]. After a complete history, physical exam, and laboratory testing, most patients are started on 50 mg orally per day [234]. For most patients, this is the safe and effective dose of naltrexone. However, in a four-month study period, the COMBINE study
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MDMI1826
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