Memantine as a Supplement to Naltrexone in Treating Heroin Dependence

In the proposed trial heroin-dependent patients undergoing detoxification will be randomly
assigned to one of two conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 20 mg
bid. Long-acting, injectable form of naltrexone (Vivitrol) will be administered once per
month (the total of three injections) while memantine or placebo will be taken daily. In
addition, patients will receive twice weekly psychosocial intervention that will include
motivational interviewing and cognitive-behavioral relapse prevention. The goal of
psychosocial intervention is to improve compliance with medication and maintain abstinence. A
double-blind trial will last twelve weeks with assessments at baseline and at each
appointment three times per week. After the completion of a double-blind study (experimental
phase), participants will continue open label treatment with Vivitrol and therapy for
additional three months (study extension phase). Repeated assessments will also be completed
one, two, and three months following the end of double-blind treatment. For the experimental
phase of the study, the primary aim is to test the efficacy of memantine in reducing early
attrition and improving outcome in opioid-dependent individuals maintained on naltrexone and
primary outcome measures will be retention in treatment by the end of the study and heroin
abstinence.

Inclusion Criteria:

1. Adult, aged 18-60.

2. Meets Diagnostic and Statistical Manual IV (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.

3. Able to give informed consent.

Exclusion Criteria:

1. Pregnancy, lactation, or failure in a sexually active woman to use adequate
contraceptive methods.

2. Active medical illness which might make participation hazardous, such as untreated
hypertension, acute hepatitis with serum glutamic oxaloacetic transaminase or serum
glutamic-pyruvic transaminase levels >2 times normal, unstable diabetes, chronic
organic mental disorder (e.g., AIDS dementia).

3. Active psychiatric disorder which 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.

4. History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone,
clonidine, or clonazepam.

5. Currently prescribed or regularly taking opiates for chronic pain or medical illness.

6. Current participation in another intensive psychotherapy or substance abuse treatment
program or currently prescribed psychotropic medications.

7. Current participation in a methadone maintenance treatment program and/or regular use
of illicit methadone (>30 mg per week).

8. History of accidental drug overdose in the last three 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.