Alcohol and Alcohol Use Disorder _ _____________________________________________________________
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]. Treatment in Special Populations Ondansetron is a serotonin antagonist and antiemetic that may block the rewarding effects of alcohol, specifically in the early-onset alcoholic subgroup. Early-onset alcoholism differs from late-onset in its association with abnormal serotonin and antisocial behavior. In a double-blind, controlled trial of ondansetron as an adjunct to cognitive-behavioral therapy, ondansetron was shown to reduce self-reported drinking and increase abstinence as compared to placebo. These results were confirmed by measure of plasma carbohydrate deficient transferring, a biomarker of alcohol consumption [361]. One hypothesis suggests that ondansetron may reduce drinking in individuals with alcohol use disorder with the LL genotype [362].
Buspirone hydrochloride is a dopamine antagonist and partial agonist for serotonin, exhibiting anxiolytic properties. In a 12-week randomized, placebo-controlled trial among 61 patients with alcohol use disorder and anxiety, buspirone was associated with slower return to heavy alcohol consumption and fewer drinking days [363]. One study found buspirone to be effective in treatment of comorbid anxiety disorder and alcohol use disorder [364]. Clozapine is an atypical antipsychotic approved to treat schizophrenia and its resultant symptoms (e.g., hallucinations, suicidal behavior). In case studies, it has shown promise in the treatment of comorbid substance use. In a study of 151 individuals with schizophrenia with comorbid substance use, 36 were given clozapine [365]. Those who abused alcohol experienced a reduction in drinks and drinking days. Other drugs under trial for use in the treatment of alcohol use disorder include varenicline and lithium. Varenicline does appear to help reduce drinking in some individuals with alcohol use disorder; however, concerns exist regarding reports of an association between the drug and an increased risk for suicidal thoughts and cardiovascular events [366]. Studies have demonstrated that varenicline helps reduce alcohol craving and consumption in patients with alcohol use disorder and in individuals with alcohol use disorder who also smoke [367; 368; 369]. None of the medications mentioned for alcohol use disorder are recommended for women who are pregnant or breastfeeding. TREATMENT OF ALCOHOL WITHDRAWAL Benzodiazepines have been used for 30 years in the United States as the primary medical treatment for alcohol withdrawal syndrome. All benzodiazepines appear similarly effective in the treatment of alcohol withdrawal syndrome [370]. Although benzodiazepines are the drugs of choice, there are concerns about the side effects and, as stated, problems of abuse, especially for outpatient detoxification. Benzodiazepines are sedatives and cause deficiencies in psychomotor abilities that, when combined with alcohol, can cause accidents and affect the ability to think clearly. However, benzodiazepines are, and have been, effective in treating alcohol withdrawal symptoms and preventing most seizures. Other regimens for alcohol withdrawal syndrome include barbiturates, propofol, and ethanol [371; 372; 373]. A desirable alternative to benzodiazepines would be a nonsedative anticonvulsant that has less potential for abuse and dependence. Valproic acid has been used in Europe safely and successfully for many years for alcohol withdrawal syndrome, but is only approved by the FDA for the treatment of mania, seizures, and migraines. Valproic acid should be used as an adjunctive therapy, not as monotherapy [370]. According to clinical reports, valproic acid is an anticonvulsant with no potential for abuse and is better tolerated by patients. Valproic acid also has less cognitive impairment and causes fewer deficiencies of psychomotor abilities than benzodiazepines;
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MDMI1826
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