Opioid Dependence
Conditions
Keywords
Heroin, Opiates, naltrexone, memantine
Brief summary
The goal of this study is to test the efficacy of memantine (a noncompetitive NMDA receptor antagonist) as an adjunct to the maintenance treatment with naltrexone in detoxified heroin-dependent individuals.
Detailed description
The primary aim of this study is to test the efficacy of memantine, a noncompetitive NMDA receptor antagonist, in reducing early attrition and improving outcome in opioid-dependent individuals maintained on naltrexone. This double-blind, 12-week trial will include heroin-dependent patients who completed detoxification. Participants will be randomly assigned to one of three conditions: naltrexone and placebo, naltrexone and memantine (15 mg bid), or naltrexone and memantine (30 mg bid). Naltrexone will be taken 3 times each week at the clinic, while memantine or placebo will be taken at home. In addition, twice each week patients will receive a psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The goal of the psychosocial intervention is to improve compliance with medication and maintain abstinence. Baseline assessments will be taken and compared to those completed at study visits, which will occur 3 times each week.
Interventions
DRUGMemantine
One arm receives 30 mg bid and the other arm receives receives 15mg bid
DRUGNaltrexone
Patients received the equivalent of 50 mg/day. Dispensed as 100 mg on Mondays and Wednesdays and 150 mg on Fridays.
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Adult, aged 18-60. * Meets DSM-IV criteria for current opiate dependence disorder of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear. * Able to give informed consent. Exclusion: * Pregnancy or breastfeeding * Failure in a sexually active woman to use adequate contraceptive methods * Active medical illness that might make participation hazardous, such as untreated hypertension, acute hepatitis with SGOT or SGPT levels \> 2 times normal, unstable diabetes, or chronic organic mental disorder (e.g., AIDS dementia) * Active psychiatric disorder that might interfere with participation or make participation hazardous, including DSM-IV schizophrenia, bipolar disorder with mania or psychosis, and depressive disorder with suicide risk or 1 or more suicide attempts within the past year. * History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone, clonidine, or clonazepam * Currently prescribed or regularly taking opiates for chronic pain or medical illness * Current participation in another intensive psychotherapy or substance abuse treatment program or currently prescribed psychotropic medications * Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone ( \> 30 mg per week) * History of accidental drug overdose in the last 3 years or any other significant history of overdose following detoxification, defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention in Treatment | Number of participants who complete 12 weeks of treatment | The number of participants who were retained and completed all 12 weeks of treatment and study participation were compared between the three study groups. |
Countries
United States
Participant flow
Recruitment details
Individuals who applied for treatment at the Columbia University's Substance Treatment and Research Service outpatient clinic in New York City were recruited for this study.
Pre-assignment details
Following consent participants were admitted to an inpatient unti at NYSPI for the purpose od detoxification and naltrexone induction. On the second day of induction they were randomized to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo plus oral naltrexone | 27 |
| Memantine 30 mg Bid Memantine 30 mg bid plus oral naltrexone | 27 |
| Memantine 15 mg Bid memantine 15 mg bid plus oral naltrexone | 27 |
| Total | 81 |
Baseline characteristics
| Characteristic | Memantine 30 mg Bid | Memantine 15 mg Bid | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 27 Participants | 27 Participants | 81 Participants |
| Age, Continuous | 42.0 years STANDARD_DEVIATION 10.3 | 41.5 years STANDARD_DEVIATION 9.4 | 40.5 years STANDARD_DEVIATION 9.6 | 41.3 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 27 participants | 27 participants | 27 participants | 81 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 20 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 27 | 17 / 27 | 10 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 1 / 27 |
Outcome results
Primary
Retention in Treatment
The number of participants who were retained and completed all 12 weeks of treatment and study participation were compared between the three study groups.
Time frame: Number of participants who complete 12 weeks of treatment
Population: All analysis were conducted based on intent-to-treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Retention in Treatment | 7 participants |
| Memantine 30 mg Bid | Retention in Treatment | 5 participants |
| Memantine 15 mg Bid | Retention in Treatment | 6 participants |
Comparison: all statistical analysis were two tailed and employed an alpha significance level of 0.05.p-value: 0.32Chi-squared