Gabapentin Treatment of Benzodiazepine Dependence

Overview[ - collapse ][ - ]

Purpose 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.
ConditionBenzodiazepine Dependence
InterventionDrug: gabapentin
Drug: Placebo
PhasePhase 2
SponsorNew York State Psychiatric Institute
Responsible PartyNew York State Psychiatric Institute
ClinicalTrials.gov IdentifierNCT01893632
First ReceivedJune 29, 2013
Last UpdatedJuly 24, 2013
Last verifiedJuly 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 29, 2013
Last Updated DateJuly 24, 2013
Start DateJuly 2013
Estimated Primary Completion DateDecember 2015
Current Primary Outcome MeasuresAbstinence from Benzodiazepine use [Time Frame: 12 weeks] [Designated as safety issue: No]Achievement of two weeks abstinence from benzodiazepine use
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleGabapentin Treatment of Benzodiazepine Dependence
Official TitleGabapentin Treatment of Benzodiazepine Dependence
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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
ConditionBenzodiazepine Dependence
InterventionDrug: gabapentin
Other Names:
NeurontinDrug: Placebo
Study Arm (s)
  • Experimental: Gabapentin
    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.
  • Placebo Comparator: Placebo
    Capsules filled with riboflavin.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment50
Estimated Completion DateDecember 2015
Estimated Primary Completion DateDecember 2015
Eligibility Criteria
Inclusion Criteria:

1. Meets DSM-IV-TR criteria for BZD dependence

2. Using BZDs a minimum of 5 days per week over the past 28 days

3. Between the ages of 18 and 60

4. Able to provide informed consent

Exclusion Criteria:

1. Any current DSM-IV-TR Axis I psychiatric disorder, other than BZD dependence, that
might require intervention over the course of the study, including schizophrenia,
bipolar disorder, major depressive disorder or panic disorder.

2. Receiving psychotropic medication other than BZDs

3. Evidence of physiological BZD withdrawal (pulse > 100; blood pressure > 140/90)

4. History of BZD withdrawal seizures or withdrawal delirium

5. History of allergic reaction to GBP

6. Pregnancy, lactation, or failure in female patients to use adequate contraceptive
methods

7. Unstable physical disorders which might make participation hazardous medical history

8. Subjects who have a current DSM-IV-TR diagnosis of other substance dependence, with
the exception of nicotine and caffeine history; dependence
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsContact: John J Mariani, MD
212-543-5987
mariani@pi.cpmc.columbia.edu
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01893632
Other Study ID Numbers6740
Has Data Monitoring CommitteeNo
Information Provided ByNew York State Psychiatric Institute
Study SponsorNew York State Psychiatric Institute
CollaboratorsNot Provided
Investigators Principal Investigator: John J. Mariani, MD New York State Psychiatric Institute
Verification DateJuly 2013

Locations[ + expand ][ + ]

New York State Psychiatric Institute
New York, New York, United States, 10032
Contact: John J Mariani, MD | 212-543-5987 | jm2330@columbia.edu
Principal Investigator: John J Mariani, MD
Recruiting