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Drug Alcohol Depend. 2013 Nov 1;133(1):80-5. doi: 10.1016/j.drugalcdep.2013.05.030. Epub 2013 Jul 1.

Naltrexone treatment for opioid dependence: does its effectiveness depend on testing the blockade?

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  • 1Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. Electronic address:



FDA approval of long-acting injectable naltrexone (Vivitrol) for opioid dependence highlights the relevance of understanding mechanisms of antagonist treatment. Principles of learning suggest an antagonist works through extinguishing drug-seeking behavior, as episodes of drug use ("testing the blockade") fail to produce reinforcement. We hypothesized that opiate use would moderate the effect of naltrexone, specifically, that opiate-positive urines precede dropout in the placebo group, but not in the active-medication groups.


An 8-week, double-blind, placebo-controlled trial (N=57), compared the efficacy of low (192 mg) and high (384 mg) doses of a long-acting injectable naltrexone (Depotrex) with placebo (Comer et al., 2006). A Cox proportional hazard model was fit, modeling time-to-dropout as a function of treatment assignment and urine toxicology during treatment.


Interaction of opiate urines with treatment group was significant. Opiate-positive urines predicted dropout on placebo and low-dose, but less so on high-dose naltrexone, where positive urines were more likely followed by sustained abstinence. Among patients with no opiate-positive urines, retention was higher in both low- and high-dose naltrexone conditions, compared to placebo.


Findings confirm that injection naltrexone produces extinction of drug-seeking behavior after episodes of opiate use. Adequate dosage appears important, as low-dose naltrexone resembled the placebo group; opiate positive urines were likely to be followed by dropout from treatment. The observation of high treatment retention among naltrexone-treated patients who do not test the blockade, suggests naltrexone may also exert direct effects on opiate-taking behavior that do not depend on extinction, perhaps by attenuating craving or normalizing dysregulated hedonic or neuroendocrine systems.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.


Long-acting injectable naltrexone; Opiate dependence; Opioid antagonist; Treatment retention; Urine toxicology

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