title: A prospective, randomized, multicenter acceptability and safety study of direct buprenorphine/naloxone induction in heroin-dependent individuals.
abstract: OBJECTIVE
  To provide controlled data on direct induction with buprenorphine/naloxone (BNX) versus indirect buprenorphine (BPN)-to-BNX induction.
  
  
  METHODS
  Phase 4, prospective, randomized, active-drug controlled, parallel-group trial consisting of a 2-day, double-blind, double-dummy induction phase followed by 26 days of open-label treatment with BNX.
  
  
  METHODS
  Nineteen sites in 10 European countries from March 2008 to December 2009.
  
  
  METHODS
  A total of 187 opioid-dependent men and women ≥ 15 years of age.
  
  
  METHODS
  The primary objective was assessment of patient response to direct and indirect BNX induction [proportion of patients receiving the scheduled 16-mg BNX dose on day 3 (i.e. first day post-induction)]. Secondary assessments included illicit drug use, treatment retention and compliance, withdrawal scale scores, and safety.
  
  
  RESULTS
  Patient response to direct- versus indirect-BNX induction was similar [direct 91.4% (85/93) versus indirect 90.4% (85/94); 95% confidence interval (CI): -7.3%, 9.2%]. Rapid dose induction (16 mg of BPN equivalent on day 2) was acceptable and 72% of patients completed treatment (day 28). There were no significant differences in secondary measures across groups. An average BNX maintenance dose of 15.3 mg across groups was associated with substantial reductions in illicit opioid use and no self-reported intravenous misuse. Treatment compliance and retention rates were similar (98.5% and 81.3%, respectively). Treatment-emergent adverse event rates were comparable: 75% versus 74% for direct- versus indirect-induction groups, respectively.
  
  
  CONCLUSIONS
  Direct buprenorphine/naloxone induction was a safe and effective strategy for maintenance treatment of opioid dependence. Response to high-dose direct buprenorphine/naloxone induction appears to be similar to indirect buprenorphine-to-buprenorphine/naloxone induction and was not associated with reports of intravenous buprenorphine/naloxone misuse.
authors.affiliation: Schering Corporation, A Division of Merck and Company, Kenilworth, NJ 07830, USA. la@biopsych.com
authors.forename: Leslie
authors.initials: L
authors.lastname: Amass
authors.forename: Vilma
authors.initials: V
authors.lastname: Pukeleviciene
authors.forename: Emilis
authors.initials: E
authors.lastname: Subata
authors.forename: António Rocha
authors.initials: AR
authors.lastname: Almeida
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Pieri
authors.forename: Pietro
authors.initials: P
authors.lastname: D'Egidio
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Stankova
authors.forename: António
authors.initials: A
authors.lastname: Costa
authors.forename: Bobby P
authors.initials: BP
authors.lastname: Smyth
authors.forename: Slavko
authors.initials: S
authors.lastname: Sakoman
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: John
authors.initials: J
authors.lastname: Strang
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D005060:Europe; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D057194:Intention to Treat Analysis; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D011446:Prospective Studies; D015819:Substance Abuse, Intravenous / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine