title: Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth With Opioid Dependence.
abstract: OBJECTIVE
  The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)--an uncommon variant of polymorphic ventricular tachycardia--that can result in syncope, ventricular fibrillation, and sudden death.
  
  
  METHODS
  Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc.
  
  
  RESULTS
  Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P < 0.0005). Variations in the QTc intervals were observed in some; however, none were above 500 milliseconds--the level at which risk for TdP becomes more significant.
  
  
  CONCLUSIONS
  In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than in DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania (SAP, AP, GW); The Children's Hospital of Philadelphia, Philadelphia, PA (VLV); Deputy Director, The Center for Clinical Trials Network, National Institute on Drug Abuse (G.S.).
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Poole
authors.forename: Anna
authors.initials: A
authors.lastname: Pecoraro
authors.forename: Geetha
authors.initials: G
authors.lastname: Subramaniam
authors.forename: George
authors.initials: G
authors.lastname: Woody
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Vetter
mesh_terms: D000293:Adolescent; D000328:Adult; D000069479:Buprenorphine, Naloxone Drug Combination / Q000008:administration & dosage / Q000009:adverse effects*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000069479:Buprenorphine, Naloxone Drug Combination