title: Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study.
abstract: OBJECTIVE
  To determine and evaluate QTc intervals in electrocardiograms (ECGs) of former heroin addicts, currently in methadone maintenance treatment (MMT), as previous reports suggest that methadone may prolong QTc intervals, thus possibly increasing the risk for Torsade de pointes (TdP).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Between January 2003 and September 2004, patients on a steady dose of methadone for at least 2 weeks were studied.
  
  
  METHODS
  This study is a subset of 153 patients, of whom 151 patients participated in a study of high methadone doses and serum levels. A total of 138 patients in MMT for a minimum of 100 days up to 10.7 years, receiving 40-290 mg/day methadone dose, participated.
  
  
  METHODS
  Patients had an ECG at the time when blood was drawn for determination of serum methadone levels at around 24 hours after the last oral methadone dose. Corrected-QT intervals (QTc) were calculated using the Bazett formula.
  
  
  RESULTS
  Of 138 patients studied, 98 (71%) were male. Mean QTc interval was 418.3 +/- 32.8 milliseconds (ms). Mean methadone dose was 170.9 +/- 50.3 mg/day and mean serum methadone level was 708.2 +/- 363.1 ng/ml. Methadone dose and serum levels did not correlate with QTc. Three patients had QTc intervals above 500 ms ('prolonged'). After 2 +/- 0.4 years of follow-up, two patients died; they were two of three patients with very prolonged QTc. Causes of death were not attributed to cardiac origin. An additional 19 patients had QTc intervals of between 450 and 499 ms ('possibly prolonged'). None of these QTc > or = 450 ms patients had any cardiac problems. Methadone doses of all 22 patients were > 120 mg/day.
  
  
  CONCLUSIONS
  Methadone maintenance is generally safe; however, the possible toxicity of high dose (> 120 mg/day) should be monitored for QTc.
authors.affiliation: Dr Miriam and Sheldon G Adelson Clinic for Drug Abuse, Treatmentand Research,, Tel-Aviv, Israel. einatp@tasmc.health.gov.il
authors.forename: Einat
authors.initials: E
authors.lastname: Peles
authors.forename: Gershon
authors.initials: G
authors.lastname: Bodner
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Vera
authors.initials: V
authors.lastname: Rados
authors.forename: Miriam
authors.initials: M
authors.lastname: Adelson
mesh_terms: D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006556:Heroin Dependence / Q000097:blood / Q000534:rehabilitation*; D006801:Humans; D008133:Long QT Syndrome / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood
chemical_list: D009294:Narcotics; D008691:Methadone