title: Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial.
abstract: BACKGROUND
  Due to potential proarrhythmic side-effects levo-alpha-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy.
  
  
  METHODS
  ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines.
  
  
  RESULTS
  Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409s +/- 0.022s versus 0.418s +/- 0.028s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1).
  
  
  CONCLUSIONS
  In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.
authors.affiliation: Department of Cardiology, University Hospital Essen, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wieneke
authors.forename: H
authors.initials: H
authors.lastname: Conrads
authors.forename: J
authors.initials: J
authors.lastname: Wolstein
authors.forename: F
authors.initials: F
authors.lastname: Breuckmann
authors.forename: M
authors.initials: M
authors.lastname: Gastpar
authors.forename: R
authors.initials: R
authors.lastname: Erbel
authors.forename: Norbert
authors.initials: N
authors.lastname: Scherbaum
mesh_terms: D000328:Adult; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006556:Heroin Dependence / Q000534:rehabilitation; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008691:Methadone / Q000009:adverse effects / Q000627:therapeutic use / Q000652:urine; D008692:Methadyl Acetate / Q000009:adverse effects* / Q000652:urine; D009294:Narcotics / Q000009:adverse effects* / Q000652:urine
chemical_list: D009294:Narcotics; D008692:Methadyl Acetate; D008691:Methadone