______________________________________________________________ Alcohol and Alcohol Use Disorder
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]. Anticonvulsants Research has demonstrated that topiramate is efficacious in decreasing heavy drinking among individuals with alcohol use disorder [354]. In a controlled study, topiramate produced significant and meaningful improvement in a wide variety of drinking outcomes [355]. Topiramate may suppress the craving and rewarding effects of alcohol [356]. In a double- blind, controlled trial, 150 patients with alcohol use disorder were randomized to escalating doses of topiramate (25–300 mg/day) or placebo. Those on topiramate had a reduction in self-reported drinking (number of drinks and drinking days), alcohol craving, and plasma y-glutamyl transferase (an indicator of alcohol consumption) [357]. Side effects of topiramate include numbness in the extremities, fatigue, confusion, paresthesia, depression, change in taste, and weight loss. Use of topiramate for alcohol use disorder is off-label [234]. Carbamazepine has proven effective for treating acute alcohol withdrawal [358]. Its side effects include nausea, vomiting, drowsiness, dizziness, chest pain, headache, trouble urinating, numbness in extremities, liver damage, and allergic reaction [234]. In a 12-month, double-blind, placebo-controlled trial, 29 patients were assigned to carbamazepine three times daily (to reach an average blood level of 6 mg/liter) or placebo. Those treated with carbamazepine showed a delay in time to first drink and a decrease in number of drinks and drinking days [359]. Oxcarbazepine is a carbamazepine derivative, with fewer side effects and contraindications, used to prevent relapse in patients with alcohol use disorder by blocking alcohol withdrawal [358]. A group of 84 patients with alcohol use disorder following detoxification were randomized to 50 mg naltrexone, 1,500–1,800 mg oxcarbazepine, or 600–900 mg oxcarbazepine for 90 days. Approximately 58.6% of the high-dose oxcarbazepine patients remained alcohol-free, a significantly larger number as compared to the low-dose (42.8%) and naltrexone groups (40.7%) [360].
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MDMI1826
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