title: Efficacy of extended-release naltrexone in patients with relatively higher severity of alcohol dependence.
abstract: BACKGROUND
  Because some literature reviews have suggested that naltrexone's benefit may be limited to less-severe alcohol dependence, and exclusively to reduction in heavy drinking rather than abstinence, we examined the efficacy of once per month, injectable extended-release naltrexone (XR-NTX 380 mg) in patients with relatively higher severity alcohol dependence.
  
  
  METHODS
  Post hoc analyses examined data from a multicenter, placebo-controlled, 24-week randomized trial of XR-NTX for alcohol dependence (N = 624). We analyzed treatment effects in alcohol-dependent patients who had higher baseline severity, as measured by: (i) the Alcohol Dependence Scale (ADS) or (ii) having been medically detoxified in the week before randomization. Efficacy was also examined via the relationship between pretreatment severity indices and reporting at least 4 days of lead-in abstinence prior to treatment-a major predictor of good outcome in the original study.
  
  
  RESULTS
  Higher severity alcohol-dependent patients, defined by the ADS, when receiving XR-NTX 380 mg (n = 50) compared with placebo (n = 47), had significantly fewer heavy-drinking days in-trial (hazard ratio=0.583; p = 0.0049) and showed an average reduction of 37.3% in heavy-drinking days compared with 27.4% for placebo-treated patients (p = 0.039). Among those who had a detoxification just prior to randomization, these reductions were 48.9% (XR-NTX 380 mg; n = 11) and 30.9% (placebo; n = 15) (p = 0.004). Subjects with at least 4 days of pretreatment abstinence (n = 82) versus those without (n = 542) had significantly higher pretreatment ADS scores (p = 0.002) and were more likely to require detoxification prior to randomization (p < 0.001). Patients with lead-in abstinence experienced significantly better maintenance of initial and 6-month abstinence.
  
  
  CONCLUSIONS
  These secondary analyses support the efficacy of XR-NTX 380 mg in relatively higher severity alcohol dependence for both reduction in heavy drinking and maintenance of abstinence, with implications for the role of adherence pharmacotherapy.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. pettinati_h@mail.trc.upenn.edu
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pettinati
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Silverman
authors.forename: John J
authors.initials: JJ
authors.lastname: Battisti
authors.forename: Robert
authors.initials: R
authors.lastname: Forman
authors.forename: Edward
authors.initials: E
authors.lastname: Schweizer
authors.forename: David R
authors.initials: DR
authors.lastname: Gastfriend
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology / Q000534:rehabilitation*; D015928:Cognitive Behavioral Therapy; D003692:Delayed-Action Preparations; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010349:Patient Compliance; D011569:Psychiatric Status Rating Scales; D013695:Temperance; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009271:Naltrexone