Behavioral Naltrexone Therapy for Promoting Adherence to Oral Naltrexone vs Extended Release Injectable Depot Naltrexone

The clinical trial now proposed will provide an initial test of the feasibility and efficacy
of the newly adapted version of Behavioral Naltrexone Therapy for Depot Naltrexone
(Depot-BNT). Treatment-seeking opiate-dependent patients will be admitted for inpatient
detoxification and induction onto oral naltrexone. Those who are successfully inducted will
be randomly assigned for a six month trial to one of two conditions: 1) Behavioral Naltrexone
Therapy for Depot Naltrexone (Depot-BNT) (N = 30), with the first dose of depot naltrexone
administered prior to discharge from hospital with monthly doses thereafter; or 2) Behavioral
Naltrexone Therapy as previously developed for promoting compliance with daily oral
naltrexone (BNT-Oral) (N = 30). All patients in both groups will be asked to attend twice
weekly outpatient therapy sessions over a six month course. This design will provide a test
of whether Depot-BNT produces superior treatment retention and drug use outcome in comparison
to our established behavioral platform for oral naltrexone, while providing experience upon
which to base revisions of Depot-BNT prior to embarking upon further Stage 2 testing.
Treatment will take place at the same sites as for our prior studies: (1) the General
Clinical Research Unit (GCRU) of New York State Psychiatric Institute (NYSPI) and (2) the
Substance Treatment and Research Service (STARS) of the Division on Substance Abuse at NYSPI.

Inclusion Criteria:

1. Age 18-60.

2. 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. If participating as an outpatient only, recent
opiate dependence must be confirmed by clinical history and/or communication with
former treatment provider.

3. Seeking treatment for heroin dependence.

4. Able to give informed consent.

Exclusion Criteria:

1. Methadone maintenance treatment or regular use of illicit methadone (> 30 mg per
week).

2. Maintenance on, or regular use of buprenorphine or other long-acting narcotic
agonists.

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

4. Active medical illness which might make participation hazardous, such as untreated
hypertension, hepatitis with SGOT or SGPT > 3 times normal, unstable diabetes.

5. 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.

6. Physiologically dependent on alcohol or sedative-hypnotics with impending withdrawal.
Other substance use diagnoses are not exclusionary. Multiple substance use is common
in this population, and such an exclusion would rule out a large proportion of the
population and limit the generalizability of the study.

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

8. Chronic organic mental disorder (e.g. AIDS dementia).

9. History of accidental drug overdose in the last 3 years as defined as an episode of
opioid-induced unconsciousness or incapacitation, whether or not medical treatment was
sought or received.

10. Currently receiving any other investigational drug, or has used any other
investigational drug within 30 days of study entry.

11. Currently prescribed or regularly taking opiates for chronic pain or medical illness
or those individuals anticipating surgical procedures which will necessitate opioid
medications.