Despite substantial advances in the development of pharmacological and behavioral interventions, alcohol dependence continues to be a significant public health problem in the U.S., and significant gaps in the treatment armamentarium remain. Conceptually, the ideal pharmacotherapy for alcohol dependence would: 1) be safe when administered to actively drinking patients;2) provide protection against alcohol withdrawal;3) promote alcohol abstinence;4) decrease craving and the risk of relapse in abstinent patients;and 5) have a low potential for abuse. No current pharmacotherapy for alcohol dependence meets these criteria and thus represents an important unmet public health need. Gabapentin is an anticonvulsant medication with limited evidence of efficacy in treating the symptoms of alcohol withdrawal and post-acute withdrawal symptoms, such as insomnia and anxiety, as well as limited evidence of efficacy as a relapse prevention agent. Gabapentin has proven to be a well-tolerated medication with a low abuse liability, thereby making it ideal for use in the outpatient setting. The proposed pilot project is to study the effects of gabapentin on the participants'use of alcohol in an abstinence-initiation model, where participants are actively using alcohol at study entry, and the change in use pattern from baseline is measured throughout the study period. The advantage of the abstinence-initiation approach is that it serves as a more accurate mirror of the most common clinical presentation of alcohol dependence: an actively-drinking patient for whom inpatient detoxification is unnecessary or unacceptable.
The specific aim of the project is to determine whether the anticonvulsant agent gabapentin is more effective than placebo in treating alcohol withdrawal symptoms and reducing alcohol consumption and promoting abstinence in alcohol-dependent patients. The primary outcome measures will be 1) the Clinical Institute Withdrawal Alcohol (CIWA-Ar) and 2) the number of the heavy drinking days (defined as any day where the number of drinks was at least 5 for men and at least 4 for women) per week as measured by the timeline follow-back method. The secondary hypothesis is that gabapentin will be superior to placebo in reducing alcohol use as measured by secondary outcomes such as amount of drinks per day, amount of drinks per drinking day, percent days abstinent and serial measurement of gamma-glutamyl transferase (GGT) serum levels. The proposed project is an 8-week randomized double-blind placebo-controlled pilot trial to evaluate the efficacy of gabapentin in the treatment of alcohol dependence in 60 outpatients. All participants will receive weekly supportive behavioral treatment that promotes abstinence from alcohol and other substances, encourages 12-step meeting attendance, and facilitates compliance with study medication. The proposed research project would be the first study of gabapentin using the abstinence-initiation model, which would be of great clinical utility if proven to be effective.
Alcohol dependence is significant public health problem in the U.S. responsible for substantial health and economic costs. The available medication treatments for alcohol dependence are limited in that no one single agent has been identified that can be administered to actively drinking outpatients, treat withdrawal, and reduce alcohol consumption. Identification of a medication that could serve these therapeutic objectives simultaneously would potentially increase the both availability and accessibility of medication treatment for alcohol dependence.
