Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00420771
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 19
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Benzodiazepine Dependence; Opioid Dependence	Drug: Gabapentin; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Pilot Trial of Gabapentin for the Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bridge Plaza Treatment and Rehabilitation Clinic	Long Island City	New York	United States	11101

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Mariani MD, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00420771
• Other Study ID Numbers: 4906/#5998R; K23DA021209
• First Posted: Jan 11, 2007
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by John Mariani MD, research psychiatrist, New York State Psychiatric Institute: Benzodiazepine; Gabapentin; Methadone
• Additional relevant MeSH terms: Opioid-Related Disorders; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	gabapentin treatment 1200 mg three times daily	Placebo condition received pills identical in appearance to experimental arm.
Period Title: Overall Study
STARTED	8	11
COMPLETED	5	7
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Gabapentin	Placebo	Total
Arm/Group Description	gabapentin treatment 1200 mg three times daily	Placebo condition received pills identical in appearance to experimental arm.	Total of all reporting groups
Overall Participants	8	11	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	11 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 25%	3 27.3%	5 26.3%
Male	6 75%	8 72.7%	14 73.7%
Region of Enrollment (participants) [Number]
United States	8 100%	11 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back
Description	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
Time Frame	data collected during 8 weeks of trial or length of participation

Outcome Measure Data

Analysis Population Description

a total of 16 participants had data available post randomization

Arm/Group Title	Active Medication	Placebo
Arm/Group Description	gabapentin treatment 1200 mg three times daily 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.	Placebo condition received pills identical in appearance to experimental arm. 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.
Measure Participants	6	10
Mean (Standard Deviation) [milligrams/day]	4.0 (4.0)	2.3 (6.7)

Adverse Events

Time Frame	8 weeks of study
Arm/Group Title	Gabapentin		Placebo
Arm/Group Description	gabapentin treatment 1200 mg three times daily		Placebo condition received pills identical in appearance to experimental arm.
All Cause Mortality
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/10 (50%)
General disorders
fatigue	3/6 (50%)	3	2/10 (20%)	2
somnalence	5/6 (83.3%)	5	2/10 (20%)	2
dizziness	4/6 (66.7%)	4	0/10 (0%)	0
other	0/6 (0%)	0	1/10 (10%)	1

Limitations/Caveats

An adequately powered double-blind trial is required to further evaluate the utility of gabapentin in treating benzodiazepine use disorder. Recruitment from more than one program is likely to be required to reach an adequate sample size.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.