Alcohol and Alcohol Use Disorder _ _____________________________________________________________
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; however, benzodiazepines have allowed for safe detoxification for patients with alcohol use disorder since they were approved. While detoxification is not treatment, and detoxification problems have not been the most important problem area in successful treatment of the patient with alcohol use disorder, these are important findings. Recognizing that relapse prevention and harm-reducing medications are safe and effective in alcohol use disorders, fewer than 10% of these patients are given medication-assisted treatment. In a 2018 meeting of the American Psychiatric Association, experts suggested [374]: • Naltrexone or acamprosate should be offered to those patients with moderate-to-severe alcohol use disorder that have a goal of reducing consumption or achieving abstinence, prefer pharmacotherapy, or have not responded to nonpharmacologic therapies, and have no contraindications. • Disulfiram should be offered to patients with severe alcohol use disorder that seek to achieve abstinence, prefer the therapy, or have not responded (or are intolerant) to naltrexone or acamprosate, and have no contraindications. Additionally, patients must understand the risks associated with consuming alcohol while on disulfiram. • Topiramate or gabapentin should be offered to patients with moderate-to-severe alcohol use disorder when they aim to reduce or achieve abstinence, prefer them to other medications, or have not responded to naltrexone or acamprosate and have no contraindications. • Benzodiazepine use is discouraged except in patients with alcohol use disorder who require treatment for acute alcohol withdrawal.
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