Treatment of Acute Alcohol Withdrawal With Gabapentin: Results From a Controlled Two-Center Trial

Abstract

A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.

Oxcarbazepine—Efficacy and Tolerability During Treatment of Alcohol Withdrawal: A Double‐Blind, Randomized, Placebo‐Controlled Multicenter Pilot Study

“…An even more advantageous design might have been a noninferiority analysis comparing the effects of CBZ and OXC. Moreover, the sample size estimation was based upon the expectation that the subjects in the OXC group would need on average 4 capsules rescue medication less than the PLA group, based on the study of Bonnet et al (2003), who chose the amount of CLO required within the first 24 hours of AWS as the primary effectiveness measure.…”

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

“…On the basis of promising data from animal experiments (Watson et al, 1997;Bailey et al, 1998;Dooley et al, 2000), preliminary clinical studies were designed to establish the possible efficacy of gabapentin in the treatment of alcohol-dependent patients affected by AWS. Open-label studies suggest a generally positive effect of gabapentin in AWS (Myrick and Anton, 1998;Bonnet et al, 1999Bonnet et al, , 2003Bonnet et al, , 2010Chatterjee and Ringold, 1999;Bozikas et al, 2002). A retrospective study analyzed both out-and inpatients treated with gabapentin (starting dose 1200 mg daily) in the treatment of AWS.…”

“…This study reported that gabapentin was no more effective than placebo in the management of AWS and did not ameliorate severe AWS. The researchers suggested that these negative results could be explained by the too low entry dose (400 mg increased to 1600 mg in the first 24 h) (Bonnet et al, 2003). On the basis of these results, the same researchers conducted an open trial to test a higher gabapentin entry dose (800 mg gabapentin loaded up to ............................................................................................................................................................ 3200 mg in the first 24 h) in patients affected by severe AWS and found that gabapentin was helpful only in reducing less severe and less complicated acute AWS (Bonnet et al, 2010).…”

Gabapentin for smoking cessation: A preliminary investigation of efficacy

“…Thus gabapentin might be the preferred medication in smokers with these comorbidities. Also, gabapentin is not contraindicated in patients with alcohol dependence or a history of seizure disorder, and it might be effective for alleviating symptoms of alcohol withdrawal (Bonnet et al, 1999;Bonnet et al, 2003;Bozikas, Petrikis, Gamvrula, Savvidou, & Karavatos, 2002;Chatterjee & Ringold, 1999;Karam-Hage & Brower, 2000Myrick, Malcolm, & Brady, 1998;Voris, Smith, Rao, Thorne, & Flowers, 2003). Gabapentin has a favorable side-effect profile, causing minor adverse effects with no serious long-term toxicity.…”