Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone

CONTEXT: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation.OBJECTIVE: To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily...

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Main Authors: Hulse, G., Morris, N., Arnold-Reed, D., Tait, Robert
Format: Journal Article
Published: American Medical Association 2009
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/5720
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author Hulse, G.
Morris, N.
Arnold-Reed, D.
Tait, Robert
author_facet Hulse, G.
Morris, N.
Arnold-Reed, D.
Tait, Robert
author_sort Hulse, G.
building Curtin Institutional Repository
collection Online Access
description CONTEXT: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation.OBJECTIVE: To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily oral naltrexone treatment.DESIGN: Seventy heroin-dependent volunteers entered a randomized, double-blind, double-placebo controlled trial with a 6-month follow-up period.PATIENTS: Eligibility criteria were DSM-IV opioid (heroin) dependence; age 18 years or older; willingness to be randomized; residing in the Perth, Western Australia, metropolitan area; and completion of preclinical screening and written consent. A total of 129 eligible participants were identified, and 70 (54%) provided informed consent and were randomized as per the study design.INTERVENTION: Participants received oral naltrexone, 50 mg/d, for 6 months (plus placebo implants) or a single dose of 2.3 g of naltrexone implant (plus placebo tablets).MAIN OUTCOME MEASURES: (1) Maintaining therapeutic naltrexone levels above 2 ng/mL; (2) return to regular heroin use (>or=4 d/wk); (3) other heroin use and abstinence; (4) use of illicit nonopioid drugs; (5) number of opiate overdoses requiring hospitalization; (6) treatment-related unexpected and expected adverse events; and (7) blood naltrexone levels (ie, pharmacokinetic profile) for recipients of active naltrexone implants.RESULTS: More participants in the oral vs the implant group had blood naltrexone levels below 2 ng/mL in months 1 (P < .001) and 2 (P = .01); in addition, more oral group participants had returned to regular heroin use by 6 months (P = .003) and at an earlier stage (median [SE], 115 [12.0] days vs 158 [9.4] days). There were 10 trial-related, unexpected adverse events. One serious adverse event, a wound hematoma, was associated with surgical implantation. Naltrexone blood levels in implant recipients were maintained above 1 and 2 ng/mL for 101 (95% confidence interval, 83-119) and 56 (39-73) days, respectively, among men and 124 (88-175) and 43 (16-79) days among women.CONCLUSIONS: The naltrexone implant effectively reduced relapse to regular heroin use compared with oral naltrexone and was not associated with major adverse events. Clinical Trial Registration anzctr.org.au Identifier: ACTRN12606000308594
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spelling curtin-20.500.11937-57202017-09-13T14:39:15Z Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone Hulse, G. Morris, N. Arnold-Reed, D. Tait, Robert naltrexone RCT heroin CONTEXT: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation.OBJECTIVE: To compare the safety and efficacy of a single-treatment sustained-release naltrexone implant with daily oral naltrexone treatment.DESIGN: Seventy heroin-dependent volunteers entered a randomized, double-blind, double-placebo controlled trial with a 6-month follow-up period.PATIENTS: Eligibility criteria were DSM-IV opioid (heroin) dependence; age 18 years or older; willingness to be randomized; residing in the Perth, Western Australia, metropolitan area; and completion of preclinical screening and written consent. A total of 129 eligible participants were identified, and 70 (54%) provided informed consent and were randomized as per the study design.INTERVENTION: Participants received oral naltrexone, 50 mg/d, for 6 months (plus placebo implants) or a single dose of 2.3 g of naltrexone implant (plus placebo tablets).MAIN OUTCOME MEASURES: (1) Maintaining therapeutic naltrexone levels above 2 ng/mL; (2) return to regular heroin use (>or=4 d/wk); (3) other heroin use and abstinence; (4) use of illicit nonopioid drugs; (5) number of opiate overdoses requiring hospitalization; (6) treatment-related unexpected and expected adverse events; and (7) blood naltrexone levels (ie, pharmacokinetic profile) for recipients of active naltrexone implants.RESULTS: More participants in the oral vs the implant group had blood naltrexone levels below 2 ng/mL in months 1 (P < .001) and 2 (P = .01); in addition, more oral group participants had returned to regular heroin use by 6 months (P = .003) and at an earlier stage (median [SE], 115 [12.0] days vs 158 [9.4] days). There were 10 trial-related, unexpected adverse events. One serious adverse event, a wound hematoma, was associated with surgical implantation. Naltrexone blood levels in implant recipients were maintained above 1 and 2 ng/mL for 101 (95% confidence interval, 83-119) and 56 (39-73) days, respectively, among men and 124 (88-175) and 43 (16-79) days among women.CONCLUSIONS: The naltrexone implant effectively reduced relapse to regular heroin use compared with oral naltrexone and was not associated with major adverse events. Clinical Trial Registration anzctr.org.au Identifier: ACTRN12606000308594 2009 Journal Article http://hdl.handle.net/20.500.11937/5720 10.1001/archgenpsychiatry.2009.130 American Medical Association unknown
spellingShingle naltrexone
RCT
heroin
Hulse, G.
Morris, N.
Arnold-Reed, D.
Tait, Robert
Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title_full Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title_fullStr Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title_full_unstemmed Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title_short Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
title_sort improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone
topic naltrexone
RCT
heroin
url http://hdl.handle.net/20.500.11937/5720