Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

Condition(s) targeted: Benzodiazepine Dependence; Opioid Dependency

Intervention: Gabapentin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: New York State Psychiatric Institute

Official(s) and/or principal investigator(s):
John J Mariani, M.D, Principal Investigator, Affiliation: Columbia University/New York State Psychiatric Institute

Overall contact:
John J Mariani, M.D, Phone: 212-543-5987, Email: jm2330@columbia.edu

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Benzodiazepine Time Line Follow Backs

Urine Toxicology

Secondary outcome:

Beck Anxiety

Hamilton Anxiety

Epworth Sleepiness Scale

Addiction Severity Index

Detailed description: We 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.

We 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. We 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. We 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

John J Mariani, M.D, Phone: 212-543-5987, Email: jm2330@columbia.edu

Bridge Plaza Treatment and Rehabilitation Clinic, Long Island City, New York 11101, United States; Recruiting
John J Mariani, MD, Phone: 212-543-5987, Email: jm2330@columbia.edu
John J Mariani, MD, Principal Investigator

Starting date: January 2007
Ending date: January 2010
Last updated: August 7, 2009