It is established that 30-50% of alcoholics relapse during the first three months after stopping drinking. Why this period is particularly vulnerable for relapse is not clear. Clinical research has confirmed impaired sleep, mood instability, and anxiety, indicators of brain hyperexcitability, during the early abstinence period. These early abstinence, or protracted withdrawal, symptoms, although not yet well characterized or quantified, are reported to be poorly tolerated by the client and are suggested to play a role in craving and relapse to alcohol use. Targeting these symptoms with a medication that does not, itself, have abuse potential is hypothesized to result in improved treatment outcome. The medication chosen to target these early abstinence symptoms is the anticonvulsant gabapentin. The proposal takes advantage of a unique program at our affiliated Veterans Administration Medical Center (VAMC) that provides residential housing and intensive substance abuse treatment for 4 weeks, as long as a client is verified as alcohol-free. This setting is ideal, since the dependent variables of interest (sleep, mood, brain activity) will not be influenced by the presence of alcohol. The hypothesis being tested is that the gabapentin-treated group, as compared to the placebo-treated group, will show improvements in behavioral (i.e., sleep, anxiety, mood) and neurological (i.e., acoustic startle and transcranial magnetic stimulation) indices. In addition, the study will explore if treatment with gabapentin during this 4-week early abstinence period decreases relapse to drinking in the month following discontinuation of pharmacotherapy and discharge from the intensive outpatient residential treatment program and will explore if gabapentin is equally effective in medically detoxified alcoholics as in non-medically detoxified alcoholics. This proposal builds on our previous experience with pharmacotherapy and behavioral/neurological characterization of acute alcohol detoxification. It extends our investigations to the early abstinence period and to a clinical treatment setting, specifically targeting protracted withdrawal symptoms with the anticonvulsant gabapentin. By using behavior, acoustic startle reflex and transcranial magnetic stimulation technologies, the study will also allow a systematic investigation of the relationship between persistent brain abnormalities and self-reported craving. This information has important implications for relapse prevention.
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