Benzodiazepine dependence is a growing public health problem for which very few evidenced-based treatment approaches are available. Approximately 683,000 individuals met past year criteria for sedative- hypnotic use disorders in the US during 2010, a prevalence greater than heroin or methamphetamine dependence. One percent of US residents report nonmedical use of sedative-hypnotic medications, a rate that has increased 20% from 2008 to 2010. The most commonly prescribed sedative-hypnotic agents are the benzodiazepines. Chronic use induces pharmacodynamic tolerance in the GABA neurotransmitter system and individuals with physiological dependence find benzodiazepines difficult to discontinue because of withdrawal or rebound symptoms, which include autonomic arousal, depression, anxiety, and insomnia. Available evidence-based treatment approaches have been primarily directed at therapeutic users of benzodiazepines who do not meet criteria for a substance use disorder, with a general consensus that the gradual taper of benzodiazepines over a period of several months is the optimal approach. However, patients with benzodiazepine dependence are typically referred for inpatient detoxification treatment, which rapidly tapers patients off benzodiazepines. Protracted withdrawal symptoms frequently persist after discharge, predisposing patients to relapse. More effective pharmacotherapeutic strategies are needed for the treatment of benzodiazepine dependence in the outpatient setting. Gabapentin has proven to be a safe and well-tolerated medication with a low abuse liability, thereby making it ideal for use in the outpatient setting. Gabapentin, if proven to be efficacious in promoting abstinence, while reducing withdrawal symptoms and cravings could broaden the range of treatment options for benzodiazepine-dependent outpatients as well as enhance treatment outcomes. The proposed Exploratory Development research project is a double-blind randomized controlled clinical trial comparing the efficacy of gabapentin to placebo for the outpatient treatment of benzodiazepine dependence. The goal of this project is to study the effects of gabapentin on the participants'benzodiazepine use in a facilitated taper-to-abstinence model, where participants will be actively using benzodiazepines at study entry, gabapentin treatment will be introduced, and participants will be counseled to gradually discontinue benzodiazepine use over the study period while gabapentin treatment is maintained. A modified version of Medical Management will be used to facilitate compliance with study medication and other study procedures, and includes clinical instruction for gradually reducing benzodiazepine use 25% per week. Benzodiazepines are not prescribed in the proposed study participants continue to obtain benzodiazepines from their own prescribed or non prescribed sources, an approach found to be feasible in the pilot study. Participants will receive voucher incentives for compliance with study visit attendance and completing study procedures, with the objective of achieving a highly compliant sample. The goal of this phase II clinical trial is to obtain preliminary evidence of efficacy and safety before conducting a larger trial.
Benzodiazepine dependence is a common in the U.S. and is a significant public health problem responsible for substantial health and economic costs. There are no evidence-based medication treatments for benzodiazepine dependence~ the only available evidence-based treatments are a slow gradual taper. The development of effective pharmacotherapy for benzodiazepine dependence would increase both the availability and accessibility of treatment for benzodiazepine dependence.
