Improved Strategies for Outpatient Opioid Detoxification

We are proposing a randomized, parallel-groups 5-week study of relapse prevention in
detoxified opioid-dependent individuals. This trial represents an initial test of the
feasibility and efficacy of an outpatient opioid detoxification strategy employing induction
onto long-acting naltrexone (Vivitrol), in combination with the recently adapted version of
Behavioral Naltrexone Therapy for Depot Naltrexone (Depot-BNT). Participants will be
randomized into one of two outpatient detoxification strategies: (1) standard 7-day
buprenorphine induction and taper from 8 mg to 0 mg (N=33), followed on Day 15 by a naloxone
challenge and a dose of long-acting injectable naltrexone (Vivitrol) (consistent with the
FDA-approved recommendation of 7 or more days between last opioid dose and Vivitrol
induction) vs. (2) a modification of our current inpatient naltrexone induction procedure,
consisting of a single day of buprenorphine followed by a washout day and 4 days of ascending
oral naltrexone doses, followed by long-acting injectable naltrexone (Vivitrol) 380 mg on Day
8 (N=67). We are seeking to obtain Vivitrol samples from Alkermes; if we are successful in
obtaining such samples, we will offer all participants who complete the study a second
injection 4 weeks after the first, and a third injection will be offered at Week 12. All
participants will receive an intensive behavioral therapy for five weeks and will be followed
for up to 24 weeks to assess the long-term outcome of the initial treatment. Study
assessments will be collected at baseline and at each study visit (twice weekly in Weeks 2-5;
weekly in Weeks 6-9 for participants who receive a second Vivitrol injection and participate
in follow-up care). Repeated assessments will also be completed at one and four months
following the end of treatment. The primary aim of this study is to test the hypothesis that
an outpatient opioid detoxification strategy using naltrexone will increase the likelihood of
successful induction onto long-acting injectable naltrexone, compared to a buprenorphine
taper in opioid-dependent patients. The primary outcome measure will be percentage in each
treatment group (oral naltrexone vs. buprenorphine taper) receiving the Vivitrol injection at
Day 8 or 15. Key secondary outcomes will be: two-week opioid abstinence during Weeks 4-5,
retention in the 8-day detoxification procedure (time to dropout) and severity of opiate
withdrawal during the first 5 weeks of treatment. We anticipate that the outpatient opioid
detoxification method developed in this project will be uniquely suited to the needs of the
rapidly expanding population of prescription opioid-abusing individuals seeking an
alternative to opioid agonist maintenance. The current proposal will also yield important
data on how to improve long-term outcomes for the buprenorphine taper method of opioid
detoxification, through the addition of long-acting naltrexone.

Inclusion Criteria:

- Meets DSM-IV criteria for current opiate dependence disorder of at least six months
duration, supported by urine toxicology OR COWS score > or =6 OR Naloxone Challenge .

- Seeking treatment for opioid dependence.

- In otherwise good health based on complete medical history and physical examination

- Able to give written informed consent.

Exclusion Criteria:

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

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

- Active medical illness which might make participation hazardous, such as untreated
hypertension, acute hepatitis with AST or ALT > 3 times normal, AIDS, unstable
diabetes.

- Severe psychiatric illness (psychotic disorder, major depression, suicide risk or 1 or
more suicide attempts within the past year.)

- Physiologically dependent on alcohol or sedative-hypnotics

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

- Chronic pain requiring opioid analgesia or anticipated surgery necessitating opioid
medications

- AIDS dementia or other chronic organic mental disorder

- Pregnancy, lactation, failure to use contraception

- 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.