Clinical trial NCT01893632
Conditions: Benzodiazepine Dependence
Keywords: Benzodiazepines clonazepam alprazolam Klonopin Xanax diazepam Valium lorazepam Ativan
Sponsor: New York State Psychiatric Institute
Start date: 2013-07-01; Completion date: 2016-04-01
Enrollment: 2 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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. 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.

Detailed description:
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.

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 nonprescribed sources.

Arms: arm 1: All study medication will be over-capsulated with riboflavin to assess compliance using quantitative fluoroscopy. All participants will take three capsules three times per day throughout the study period. During week 1, GBP will be titrated over a five-day period to the dose target (GBP 1200 mg three times daily) or the maximum tolerated dose. Medication dosing will continue at GBP 1200 mg three times daily or placebo through the end of the study period (week 12). Dose reductions will be made for tolerability if necessary. arm 2: Capsules filled with riboflavin.
Interventions: intervention 1: gabapentin intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents: