Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

April 22, 2019 updated by: John Mariani MD, New York State Psychiatric Institute

A Randomized Controlled Pilot Trial of Gabapentin for the Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

The aim of this project is to study the use of gabapentin in reducing benzodiazepine abuse in methadone maintenance patients. A second aim is to study the effects of gabapentin on craving, mood, anxiety, and sleep disturbance in methadone maintenance patients abusing benzodiazepines. The proposed protocol is a randomized, double-blind, placebo-controlled pilot outpatient trial of gabapentin in the treatment of benzodiazepine abuse in methadone maintenance patients. All subjects will receive weekly manual-guided psychotherapy directed at achieving abstinence and improving current functioning. The primary outcome measure, benzodiazepine use, will be assessed weekly by a combination of self-report (time line follow-back method) and urine toxicology. Associated psychological symptoms of craving, mood, anxiety, and sleep disturbance, will be assessed by a combination of clinician and self-rated instruments.

The investigators hypothesize that individuals receiving methadone maintenance treatment who are abusing (nonprescribed use) benzodiazepines have difficulty in reducing or discontinuing benzodiazepine use because of the significant anxiety, mood, and sleep disturbance symptoms that accompany reduction in use. Gabapentin, an anticonvulsant which has anxiolytic and sedating properties, may alleviate the symptoms associated with a reduction in benzodiazepine abuse and make the achievement of abstinence more likely when administered in the setting of an active psychotherapy condition.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators will recruit individuals with current benzodiazepine abuse or dependence, as defined by the DSM-IV, who are receiving methadone maintenance treatment at the Bridge Plaza Treatment and Rehabilitation Clinic. The initial step in recruitment for all patients will be a referral from a clinic counselor.

The investigators plan to enroll 86 participants into the study. Both males and females will be recruited. The distribution of benzodiazepine abuse in methadone maintenance populations with regard to race and gender is not well studied.The investigators expect the gender and racial distribution of subjects to reflect the demographic nature of the Bridge Plaza Treatment and Rehabilitation Clinic; which is approximately 33% Caucasian, 33% African-American, and 33% Hispanic; and 40% female. The investigators will make every effort to recruit minority patients in order to ensure the ability to generalize our findings to the overall treatment population.

All patients will begin medication at the start of the study. Subjects will take medication twice each day, once in the morning and once in the evening. All tablets (placebo and study medication) will be over-capsulated with riboflavin to measure compliance. The placebo group will have a dosing schedule that is identical to the gabapentin group (i.e., they will take the same number of pills each day). Medication will be dispensed weekly in individual vials identified by patient, with dosing instructions written on the outside of the vials. Patients in the placebo group will not receive gabapentin at any time during the study. Gabapentin will be administered in 400 mg tablets; placebo tablets will appear identical to the gabapentin tablets. Gradual increases in medication doses are used in order to minimize side effects and enhance compliance. At the start of week 1, the group receiving gabapentin will be administered at 400 mg three-times a day. This dose will be increased to 800 mg three-times a day at week 2 and increased to 1200 mg three-times a day at the start of week 3. The dose will continue at 1200 mg three-times a day for weeks 3 through 8. Dose reductions for tolerability will be made by the research psychiatrist in coordination with the research pharmacy. All patients must take a minimum of gabapentin/placebo 400 mg BID to remain in the study.

Both the active and placebo medication capsules will contain riboflavin, which will allow the clinic to verify that the study medication is being taken correctly and absorbed by the body. Urine samples obtained weekly will be examined under a UV lamp in order to observe any fluorescence signifying the consumption of the study capsules. The patient will consume approximately 100 mg of riboflavin daily.

The goal of compliance enhancement therapy is to achieve high quality supportive treatment as well as consistency between treatment groups. Treatment will be delivered in 9 individual sessions over 9 weeks. Sessions will last approximately 30 minutes and will be structured, focused on setting abstinence from benzodiazepine use as a goal, patient compliance, and current functioning. The therapist will promote a positive supportive therapeutic relationship with the treatment goal of encouraging abstinence from benzodiazepines and adherence to study visits and medication.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Long Island City, New York, United States, 11101
        • Bridge Plaza Treatment and Rehabilitation Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men and women between the ages of 18-65 who meet DSM-IV criteria for benzodiazepine abuse or dependence, and opioid dependence, and are being treated for opioid dependence with methadone.
  • Individuals seeking treatment for benzodiazepine abuse or dependence.
  • Individuals capable of giving informed consent and capable of complying with study procedures.
  • Individuals must have current benzodiazepine use.

  • Individuals must report using, benzodiazepines an average > 4 days per week over the past 28 days. The average amount of benzodiazepine used per using day must be > lorazepam 4 mg/day or its equivalent

    (1 mg lorazepam = 0.25 mg clonazepam = 0.5 mg alprazolam = 5 mg diazepam = 10 mg chlordiazepoxide)

  • Women of child-bearing age will be included provided that they are not pregnant, based on the results of a blood pregnancy test done at the time of screening and agree to use a method of contraception with proven efficacy and not to become pregnant during the study.

Exclusion Criteria:

  • Subjects with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment that are unstable or would be disrupted by study medication or by an effort to discontinue benzodiazepines. Disorders that are stable on psychotherapy or pharmacotherapy will not be exclusionary.
  • Individuals with evidence of acute physiological benzodiazepine withdrawal.
  • Individuals with a history of seizures during alcohol or sedative-hypnotic withdrawal.
  • Individuals with a history of requiring pharmacologic detoxification from alcohol or sedative-hypnotic agents in the past year.
  • Individuals meeting DSM IV criteria for current cocaine dependence as their primary substance use disorder diagnosis.
  • Unstable physical disorders that might make participation hazardous such as uncontrolled hypertension and tachycardia (SBP > 150 mm Hg, DBP > 90 mm Hg, or a sitting quietly HR > 100 bpm), acute hepatitis (patients with chronic mildly elevated transaminase levels [2-3 x upper limit of normal] are acceptable) or poorly controlled diabetes. Kidney disease or impaired kidney function that would interfere with the excretion of gabapentin is exclusionary.
  • Patients currently taking prescribed psychotropic medications, other than methadone or medications prescribed for pain syndromes, that would be disrupted by study medication or by an effort to discontinue benzodiazepines. Anticonvulsants prescribed for pain syndromes are exclusionary.
  • Patients with a known sensitivity to gabapentin.
  • Individuals who have exhibited suicidal or homicidal behavior within the past two years or have current active suicidal ideation.
  • Women who are pregnant or nursing.
  • Individuals physiologically dependent on any other drugs (excluding nicotine, caffeine, methadone).
  • Individuals currently prescribed gabapentin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gabapentin
gabapentin treatment 1200 mg three times daily
Drug: Gabapentin
For the first week, one 400 mg Gabapentin capsule taken 3 times per day. For the second week, two 400 mg Gabapentin capsules taken 3 times per day. For the third week through the eighth week, three 400 mg Gabapentin capsules taken 3 times per day. For the ninth and last week, two 400 mg Gabapentin capsules taken 3 times per day for 3 days, then one 400 mg Gabapentin capsule taken 3 times per day for 4 days. Placebo study medication appears identical to active medication and is prescribed with an identical dosing schedule.
Other Names:
  • Neurontin
Placebo Comparator: Placebo
Placebo condition received pills identical in appearance to experimental arm.
Drug: Placebo
placebo comparator appears identical to active medication and is prescribed with an identical dosing schedule with a maximum dose of 400mg taken three times per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back
Time Frame: data collected during 8 weeks of trial or length of participation
Comparing the mean reduction change in Benzodiazepine use per day when comparing the baseline week prior to study entry to the last week of study participation based on the Time Line Follow Back
data collected during 8 weeks of trial or length of participation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: John J Mariani, M.D, Columbia University/New York State Psychiatric Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

January 8, 2007

First Submitted That Met QC Criteria

January 8, 2007

First Posted (Estimate)

January 11, 2007

Study Record Updates

Last Update Posted (Actual)

April 24, 2019

Last Update Submitted That Met QC Criteria

April 22, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4906/#5998R
  • K23DA021209 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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