Alcohol and Alcohol Use Disorder _ _____________________________________________________________
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 demonstrated efficacy of naltrexone at a dose of 100 mg daily [343]. Some treatment providers give patients a naltrexone identification card or ask them to order a MedicAlert bracelet that clearly indicates that they are maintained on an opioid antagonist, so if they need an opiate drug or medication for pain relief, the dose of the pain medication can be adjusted higher. Meta-analyses have revealed that approximately 70% of previous clinical trials that measured reductions in “heavy or excessive drinking” demonstrated an advantage for prescribing naltrexone over placebo [344]. In another trial, naltrexone was determined to have the greatest impact on reducing daily drinking when craving for alcohol was highest [345]. The approved dose of the extended-release formulation is 380 mg IM once per month. Pretreatment with oral naltrexone is not required before induction onto extended-release injectable naltrexone [325]. The most common side effects of naltrexone are light- headedness, diarrhea, dizziness, and nausea. Pain or tenderness at the injection site is a side effect unique to the extended- release injectable formulation [325]. Most side effects tend to disappear quickly in most patients. Naltrexone is not recommended for patients with acute hepatitis or liver failure, for adolescents, or for pregnant or breastfeeding women [325; 343]. Weight loss and increased interest in sex have been reported by some patients. In general, patients maintained on opioid antagonists should be treated with nonopioid cough, antidiarrheal, headache, and pain medications. The patient’s family or physician should call the treating physician if questions arise about opioid blockade or analgesia. It is important to realize that naltrexone is not disulfiram; drinking while maintained on naltrexone does not produce side effects or symptoms. Naltrexone works best when it is used in the context of a full spectrum of treatment services, possibly including traditional 12-step fellowship-based treatments. Studies show also that naltrexone is effective when coupled with CBT. Patients receiving medical management with naltrexone, CBT, or both fared better on drinking outcomes [343].
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MDMI1826
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