A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal

Abstract

Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.

The effectiveness of pharmacological approaches in the treatment of alcohol withdrawal syndrome (AWS): a literature review

“…There were no statistically significant results comparing rates of alcohol withdrawal seizures (Soloman et al . 1983, Wilson & Vulcano 1985), although chlordiazepoxide performed better in a relatively small study (40 participants) by Ritson & Chick (1986); no statistically significant variation in studies measuring alcohol withdrawal delirium (Miller & McCurdy 1984, Wilson & Vulcano 1985, Anton et al . 1997), although Kumar et al .…”

“…1997), although Kumar et al . (2009) found diazepam performed better; no statistically significance in CIWA‐Ar scores at 48 h and at the end of treatment (Anton et al . 1997, Jauhar & Anderson 2000, Kumar et al .…”

“…1997, Jauhar & Anderson 2000, Kumar et al . 2009), and doctors' assessment of efficacy resulted in no statistically significant results (Kolin & Linet 1981, Wilson & Vulcano 1985) although chlordiazepoxide was favoured (Anton et al . 1997); and no statistically significant result observed in patient assessed efficacy (Kolin & Linet 1981).…”

Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE‐4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department

“…15 Specific to pharmacologic therapy for AUD, previous studies show that less than 10% receive treatment, 89,90 despite a high level of screening in health care settings. 15 Several anticraving medication options exist 91,92 ; this guideline focuses on naltrexone and acamprosate because these agents have Food and Drug Administration (FDA) approval for this indication, and gabapentin, 12,[93][94][95] though off label for use in patients with AUD, is very commonly used.…”

A Pilot Open Randomized Trial of Valproate and Phenobarbital in the Treatment of Acute Alcohol Withdrawal

“…In more recent work, Anton et al 15 demonstrated in a randomized, controlled trial that treatment with either abecarnil, a benzodiazepine receptor partial agonist, or diazepam provided a similar marked reduction in withdrawal symptoms in 49 alcohol‐dependent inpatients with moderate uncomplicated alcohol withdrawal symptoms over a 5‐day detoxification period. Flumazenil infusion in dogs chronically treated with abecarnil results in mild abstinence symptoms compared with dogs chronically treated with diazepam, 16 suggesting that partial agonists at central benzodiazepine receptors may also have reduced capacity to induce dependence.…”