title: The QTc effect of low-dose methadone for chronic pain: a prospective pilot study.
abstract: OBJECTIVE
  Methadone is associated with QT prolongation and serious cardiac complications, but this has been primarily demonstrated in opioid dependent patients receiving moderate to high doses. This study investigates the effect of low-dose methadone on the QTc interval in a chronic pain population.
  
  
  METHODS
  We conducted a prospective cohort study in a chronic pain clinic including 82 patients receiving methadone and 102 patients receiving non-methadone opioid therapy.
  
  
  METHODS
  We analyzed automated QTc calculations from 12-lead electrocardiograms at baseline and during the subsequent 6 months. The primary outcome of interest was the incidence of QTc greater than 470 milliseconds or an increase from baseline of greater than 60 milliseconds.
  
  
  RESULTS
  The methadone group did not manifest an overall higher frequency of QTc > 470 milliseconds (6% for the methadone group vs 5% for controls, P = 0.722) or an increase in the QTc of > 60 milliseconds (4% for the methadone group vs 4% for controls, P = 0.94). In the first month after initiating methadone, patients demonstrated an increase in QTc compared to controls (5% for the methadone group vs 0% for the controls, P = 0.073) but the difference disappeared in the third and sixth months.
  
  
  CONCLUSIONS
  Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Samuel
authors: http://orcid.org/0000-0002-7484-7613
authors: S
authors: Grodofsky
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Emmanuel
authors: E
authors: Edson
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Stephanie
authors: S
authors: Huang
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.|Center for Pharmacoepidemiology Research and Training, University of Pennsylvania.
authors: Rebecca M
authors: RM
authors: Speck
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Justin
authors: J
authors: Hatchimonji
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Kim
authors: K
authors: Lacy
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.|Center for Pharmacoepidemiology Research and Training, University of Pennsylvania.|Department of Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania.
authors: John T
authors: JT
authors: Farrar
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania.
authors: Michael A
authors: MA
authors: Ashburn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D059350:Chronic Pain / Q000188:drug therapy* / Q000453:epidemiology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: Chronic Opioid Therapy; Methadone; QTc Prolongation