Effectiveness of Naltrexone and Lofexidine in Treating Detoxified Heroin Addicts - 1

Stress is one of the more common reasons cited by addicts for continual drug use and
relapse. Naltrexone treatment of opiate addicts suffers from high rates of drop-out and
relapse. This may be a result of naltrexone's inability to reduce symptoms of stress during
early recovery. Treatment approaches that target both drug-induced and stress-induced
relapse may prove to be more beneficial than targeting drug-induced relapse alone.
Lofexidine is a drug that reduces the physical symptoms of opiate withdrawal and may prove
to have stress-reducing capabilities. The purpose of this study is to determine the maximal
safe dose of lofexidine tolerated in naltrexone-treated opiate addicts and to find an
optimal lofexidine induction schedule. The study will also assess any side effects that
occur during a discontinuation phase of lofexidine.

This pilot study will last a total of 8 weeks. Recently detoxified opiate dependent
participants who are eligible for naltrexone treatment will enter a 4-week single-blind dose
tolerability phase, during which participants will receive naltrexone and 1 of 3 twice-daily
lofexidine induction schedules. All participants will be required to remain in the clinic
for 2 hours immediately following dosing in order to monitor vital signs and side effects.
Study visits will occur three times each week, at which time naltrexone medication for
self-administration will be handed out and participants will be evaluated in terms of
tolerability to treatment. After the 4 weeks of treatment, a double-blind lofexidine
detoxification phase using a 5-day taper will occur. Participants will be randomly assigned
to one of two maintenance-taper schedules. The first group will undergo a 5-day tapering,
followed by a placebo for three weeks, followed by a 5-day tapering during Week 4.
Withdrawal symptoms and side effects will be evaluated.

Inclusion Criteria:

- Meets DSM-IV criteria for opiate dependence

- Use of heroin at least 3 times per week during the 3 months prior to entering opiate
detoxification

- Documented positive urine toxicology test for opiates

- Successful initiation on naltrexone treatment as indicated by stabilization on 50 mg
of naltrexone once a day

- Reads English

Exclusion Criteria:

- Regular use of anticonvulsants, sedatives/hypnotics, prescription analgesics,
antihypertensives (including clonidine), antirythmics, antiretroviral medications,
and tricyclic antidepressants

- Psychotic or otherwise severely psychiatrically disabled (e.g., suidical, homicidal,
currently manic)

- Abstinent from opiates for more than four weeks prior to naltrexone initiation

- Any medical problems that might make naltrexone treatment unsafe, such as
hepato-cellular injury as evidenced by abnormal liver enzyme tests (including SGOT,
SGPT, and GGT levels greater than three times normal) and a history of cirrhosis

- Hypotension with a resting blood pressure below 90/50 mm Hg

- Pregnant, breastfeeding, or refusal to use a reliable form of contraception
throughout the study