title: The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia.
abstract: BACKGROUND
  Opioid dose escalation may cause hyperalgesia, mediated by the N-methyl-D-aspartate (NMDA) pathway. Methadone is an atypical opioid that inhibits hyperalgesia through NMDA-blockade, especially at low doses.
  
  
  OBJECTIVE
  To evaluate the efficacy of using very-low-dose methadone as the sole long-acting opioid agent in a hospice practice.
  
  
  METHODS
  A retrospective, observational study of the use of methadone, ≤15 mg daily, with as-needed short-acting opiates. Adjuvant nonopioid medications included haloperidol, which may have NMDA-blocking effects.
  
  
  METHODS
  We reviewed the records of 240 patients admitted to a community-based hospice from July 1, 2011 to April 1, 2012, with data collected until hospice discharge or until April 30, 2012.
  
  
  METHODS
  Descriptive statistics were used to summarize patient demographics, medication regimens, and reported pain scores measured on a numeric rating scale from 0 to 10.
  
  
  RESULTS
  All patients received short-acting opiates, in a morphine-equivalent dose of 5 mg every 4 hours as needed, while 40% also received methadone at a median daily dose of 5 mg. Of those on methadone, almost half received scheduled haloperidol. The population had a median reported pain score of 0 and a peak score of 3, with similar results seen for cancer and noncancer groups. Two-thirds of patients never reported a pain score greater than 3.
  
  
  CONCLUSIONS
  The use of very-low-dose methadone in conjunction with adjuvant haloperidol resulted in excellent pain control without dose escalation or opioid-induced hyperalgesia, for both cancer and noncancer diseases. We conclude that low-dose methadone should be part of first-line treatment in palliative pain management.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. salpeter@stanford.edu
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Salpeter
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Buckley
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D002140:California; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage; D017051:Hospice Care; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008485:Medical Audit; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D059408:Pain Management / Q000379:methods*; D012189:Retrospective Studies
chemical_list: D000701:Analgesics, Opioid; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D006220:Haloperidol; D008691:Methadone
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