The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia

J Palliat Med. 2013 Jun;16(6):616-22. doi: 10.1089/jpm.2012.0612. Epub 2013 Apr 4.

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.

Design: 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.

Setting/subjects: 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.

Measurements: 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.

Conclusion: 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.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • California
  • Dose-Response Relationship, Drug*
  • Excitatory Amino Acid Agonists
  • Female
  • Haloperidol / administration & dosage
  • Hospice Care*
  • Humans
  • Hyperalgesia / chemically induced
  • Hyperalgesia / prevention & control*
  • Male
  • Medical Audit
  • Methadone / administration & dosage*
  • Methadone / adverse effects
  • Middle Aged
  • N-Methylaspartate / antagonists & inhibitors
  • Pain Management / methods*
  • Retrospective Studies

Substances

  • Analgesics, Opioid
  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Haloperidol
  • Methadone