Naltrexone treatment for opioid dependence: Does its effectiveness depend on testing the blockade?
- a Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA
- b Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, Unit 51, New York, NY 10032, USA
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.
- Long-acting injectable naltrexone;
- Opiate dependence;
- Opioid antagonist;
- Treatment retention;
- Urine toxicology
Figures and tables from this article:
- Placebo (N = 17) is the reference group, against which the low dose-192 mg (N = 19), and high dose-384 mg (N = 21) conditions are contrasted. Urine toxicology, measured at twice-weekly clinic visits, was scored as a dichotomous covariate in this analysis as positive if one or more urines was positive for opioids during the trial, and negative otherwise (negative is the reference group). Values in the table are the regression coefficients for each term in the model, corresponding significance levels, and the point estimate of the hazard ration and its 95% confidence limits. The significant low-dose naltrexone-by-urine interaction term, indicates that the effect of low-dose naltrexone differs between patients with vs. without a positive urine; when urine is positive dropout is similar (and high) on low-dose naltrexone and placebo, while when urines are all negative, dropout rate is low on low-dose naltrexone (compared to high dropout on placebo) and approaches the low dropout rates for the high-dose naltrexone condition.
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- Fuente: Drug and Alcohol Dependence