title: Naltrexone treatment for opioid dependence: does its effectiveness depend on testing the blockade?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. Electronic address: mas23@columbia.edu.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.forename: Adam
authors.initials: A
authors.lastname: Bisaga
authors.forename: John J
authors.initials: JJ
authors.lastname: Mariani
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.forename: Frances R
authors.initials: FR
authors.lastname: Levin
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Edward V
authors.initials: EV
authors.lastname: Nunes
mesh_terms: D000293:Adolescent; D000328:Adult; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D016016:Proportional Hazards Models
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009271:Naltrexone
keywords: Long-acting injectable naltrexone; Opiate dependence; Opioid antagonist; Treatment retention; Urine toxicology