Depot naltrexone: long-lasting antagonism of the effects of heroin in humans - PubMed (original) (raw)

Clinical Trial

. 2002 Feb;159(4):351-60.

doi: 10.1007/s002130100909. Epub 2001 Nov 1.

Affiliations

Clinical Trial

Depot naltrexone: long-lasting antagonism of the effects of heroin in humans

Sandra D Comer et al. Psychopharmacology (Berl). 2002 Feb.

Abstract

Rationale: 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.

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Figures

Fig. 1

Fig. 1

Mean plasma levels of naltrexone (left panel) and 6-β-naltrexol (right panel) as a function of depot naltrexone dose and days after administration of depot naltrexone. Data points represent the mean across 6 participants per group. Error bars represent±1 SEM

Fig. 2

Fig. 2

Mean peak VAS ratings of “Good Drug Effect” after administration of heroin (0–25 mg) as a function of depot naltrexone dose and study week (week 1: left panel; week 6: right panel). Maximum rating=100 mm. Data points represent mean peak ratings (_n_=6 per group). Error bars represent±1 SEM. * Indicates significant differences from week 1

Fig. 3

Fig. 3

Mean total scores on the Subjective Opioid Withdrawal Scale (SOWS) after administration of heroin as a function of depot naltrexone dose and study week. Maximum score=64. All other details are as in Fig. 2

Fig. 4

Fig. 4

Mean trough pupil diameter after administration of heroin as a function of depot naltrexone dose and study week. All other details are as in Fig. 2

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