title: Prospective study of QTc changes among former opiate addicts since admission to methadone maintenance treatment: benzodiazepine risk.
abstract: OBJECTIVE
  To prospectively evaluate QTc changes among methadone maintenance treatment (MMT) patients.
  
  
  METHODS
  All 512 opiate addicts newly admitted to 2 MMT clinics had been prospectively studied for 4.5 years. Ninety-one patients were excluded because they were admitted from other MMTs, and 26 were excluded because their first electrocardiogram was performed following 28 days in MMT; therefore, 421 were studied. QTc values were again performed either after (A) a steady methadone dose for at least 3 months and negative urine tests for opiates, cocaine, amphetamines, cannabis, benzodiazepine; or after (B) same as for (A) but with positive urine tests for cannabis and/or benzodiazepine.
  
  
  RESULTS
  Mean QTc intervals were not related to benzodiazepine or cocaine use on admission. QTc interval was significantly prolonged from the baseline to steady methadone dose (424.5 ± 23.2 ms and 438.6 ± 26.6 ms, respectively) but not affected by methadone dose (<100 or ≥100 mg/d) or by the time to achieve a steady methadone dose (between 3 months and >2 years). QTc prolongation was greater among patients whose urine tested positive for benzodiazepine on a steady dose (P = 0.003). No additional prolongation was observed in 49 patients who achieved a steady methadone dose less than 1 year in MMT and had additional follow-up. Two patients who were benzodiazepine abusers died for undefined reasons.
  
  
  CONCLUSIONS
  There is significant QTc prolongation during early MMT with no apparent clinical significance. A combination of benzodiazepine and methadone should be monitored.
authors.affiliation: From the Dr Miriam and Sheldon G. Adelson Clinics for Drug Abuse Treatment and Research (EP, MA), Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Dr Miriam and Sheldon G. Adelson Clinics for Drug Abuse Treatment and Research (SL, MA), Las Vegas, NV; Laboratory of the Biology of Addictive Diseases (MJK, MA), The Rockefeller University, New York, NY.
authors.forename: Einat
authors.initials: E
authors.lastname: Peles
authors.forename: Shirley
authors.initials: S
authors.lastname: Linzy
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Miriam
authors.initials: M
authors.lastname: Adelson
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D007557:Israel; D008133:Long QT Syndrome / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D001569:Benzodiazepines; D008691:Methadone