Depot naltrexone: long-lasting antagonism of the effects of heroin in humans.
BACKGROUND
Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A sustained-release form of naltrexone may improve compliance.


OBJECTIVE
The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex).


METHODS
Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week, while placebo could be administered on any day. Subjective, performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the high dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose.


RESULTS
The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects.


CONCLUSIONS
These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.
Comer
Sandra D
SD
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. sdc10@columbia.edu
Collins
Eric D
ED
Kleber
Herbert D
HD
Nuwayser
Elie S
ES
Kerrigan
James H
JH
Fischman
Marian W
MW
D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006556:Heroin Dependence / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009294:Narcotics / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects / Q000502:physiology
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D003932:Heroin