title: A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial.
abstract: OBJECTIVE
  Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment.
  
  
  METHODS
  This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs.
  
  
  RESULTS
  Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms.
  
  
  CONCLUSIONS
  A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Kakko
authors.forename: Leif
authors.initials: L
authors.lastname: Grönbladh
authors.forename: Kerstin Dybrandt
authors.initials: KD
authors.lastname: Svanborg
authors.forename: Joachim
authors.initials: J
authors.lastname: von Wachenfeldt
authors.forename: Christian
authors.initials: C
authors.lastname: Rück
authors.forename: Bob
authors.initials: B
authors.lastname: Rawlings
authors.forename: Lars-Håkan
authors.initials: LH
authors.lastname: Nilsson
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000328:Adult; D001521:Behavior Therapy; D002047:Buprenorphine / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D003932:Heroin / Q000652:urine; D006556:Heroin Dependence / Q000534:rehabilitation*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D010349:Patient Compliance; D010352:Patient Dropouts; D012720:Severity of Illness Index; D016037:Single-Blind Method; D015813:Substance Abuse Detection; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009270:Naloxone; D002047:Buprenorphine; D003932:Heroin; D008691:Methadone