______________________________________________________________ Alcohol and Alcohol Use Disorder
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]. Acamprosate Acamprosate (Campral) is a synthetic compound that has a chemical structure similar to that of the naturally occurring amino acid neurotransmitters taurine and GABA [234]. Because chronic alcohol use is associated with decreased GABA and glutamate activity, a hyperexcitable glutamate system is one possible alcohol withdrawal mechanism. Glutamate systems may become unstable for 12 months after a person stops drinking. In a review of published, double-blind, placebo- controlled clinical trials evaluating the safety and efficacy of acamprosate in the treatment of alcohol use disorder, Mason reported that acamprosate appeared to improve treatment completion rate, abstinence rate and/or cumulative abstinence during treatment, and time to first drink, than placebo [346]. The effect on abstinence, combined with an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol use disorder. A dose of 2,000
mg/day is associated with the greatest efficacy regardless of body weight [347]. It is important to note that medication in combination with therapies can improve outcomes. In July 2004, after many years of safe use in Europe and around the world, the FDA approved the use of acamprosate for the maintenance of alcohol abstinence [333]. As in the case of naltrexone, acamprosate reduces the reinforcing (pleasurable) effects of alcohol to reduce craving. Oral dosing is two 333-mg delayed-release tablets three times daily [234; 325]. Common side effects include diarrhea, anxiety, insomnia, nausea, dizziness, and weakness. Some research indicates that acamprosate may worsen depression and/or suicidal ideation; so, patients with a history of major depression should be monitored closely or prescribed a different medication [234]. Acamprosate is contraindicated in patients with severe renal impairment [234; 325]. Due to risk of diminished renal function in patients 65 years of age and older, baseline and frequent renal function tests should be performed in this population. Dose reductions also may be necessary [325]. The effectiveness of acamprosate in promoting abstinence has not been demonstrated in individuals who have not completed detoxification or who have not achieved alcohol abstinence before beginning treatment [325]. An analysis of many studies of acamprosate showed a benefit in maintaining abstinence when coupled with CBT [343]. A systematic review found similar benefit [348]. Results of other research into the effectiveness of acamprosate have been mixed. One study showed no improvement in measures of psychological well-being or health status when compared to treatment with placebo. Another study demonstrated both safety and effectiveness of acamprosate for treating alcohol use disorder [349]. Baclofen Baclofen is a GABA agonist that may prove to be a unique therapeutic alternative to reduce alcohol craving and consumption. In a small, 12-week trial, patients with alcohol use disorder were given 10 mg of baclofen three times daily paired with motivational enhancement therapy. Patients experienced a reduction in number of drinks, drinking days, anxiety, and craving [350]. In a study of patients with alcohol use disorder and liver cirrhosis, baclofen was also found to work favorably in maintenance of alcohol abstinence. Seventy-one percent of baclofen-treated patients maintained abstinence as compared with 29% of the placebo group [351]. A 2018 meta-analysis of 12 randomized controlled trials that compared the efficacy of baclofen to placebo found that baclofen was associated with higher rates of abstinence than placebo but that its effects were not superior to placebo in increasing the number of abstinent days or in decreasing heavy drinking, craving, depression, or anxiety [352]. A 2023 systematic review of 17 randomized controlled trials involving 1,818 participants found that baclofen reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. The agent was not found to reduce the number of heavy drinking days or the number of drinks per drinking days [353].
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MDMI1826
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