A phase I study of D-methadone in patients with chronic pain Journal Article

Authors: Moryl, N.; Tamasdan, C.; Tarcatu, D.; Thaler, H. T.; Correa, D.; Steingart, R.; Payne, R.; Obbens, E.
Article Title: A phase I study of D-methadone in patients with chronic pain
Abstract: D-Methadone is the d optical isomer of racemic mixture (DL-methadone) used clinically to treat pain and addiction in the United States. D-Methadone is practically devoid of opioid activity but maintains N-methyl-D-aspartate (NMDA) receptor antagonism. Evidence from extensive preclinical studies suggests that NMDA receptor antagonists attenuate neuronal plasticity, reverse opioid analgesic tolerance, and alleviate chronic pain states. The authors conducted a phase I open label study of D-methadone administered for the first time to patients with chronic pain to determine the safety and tolerability of D-methadone. In addition to their long-term regimen of opioids, the patients received 40 mg of D-methadone twice daily for 12 days. Analgesia and toxicity were recorded by the patients in a daily diary and assessed in clinic on days 1, 8, and 12. Eight patients of the 10 enrolled completed the study. Pain scores on Edmonton Symptom Assessment System (ESAS) did not change between days 1 and 12, but five of eight patients (62.5 percent) characterized D-methadone as moderately or very effective in relieving pain on the Global Assessment for pain. Five of the eight patients (62.5 percent) who completed the study requested to start treatment with commercially available methadone (DL-racemic methadone) after completing the study. D-Methadone at the dose of 40 mg PO Q 12 hours was well tolerated. Perspective: This is the first clinical study of D-methadone in patients suffering from chronic pain. Additional phase I and phase II studies are needed to confirm its safety and analgesic effects. If D-methadone is well tolerated, it is likely to become a useful adjuvant to the treatment of a wide spectrum of pain syndromes.
Keywords: clinical trial; prospective study; prospective studies; narcotic analgesic agent; chronic pain; phase 1 clinical trial; methadone; analgesics, opioid; humans; human
Journal Title: Journal of Opioid Management
Volume: 12
Issue: 1
ISSN: 1551-7489
Publisher: Weston Medical Publishing, LLC  
Date Published: 2016-01-01
Start Page: 47
End Page: 55
Language: English
DOI: 10.5055/jom.2016.0311
PUBMED: 26908303
PROVIDER: scopus
Notes: Article -- Export Date: 1 July 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Denise D Correa
    64 Correa
  2. Natalia Moryl
    34 Moryl
  3. Richard Payne
    53 Payne
  4. Eugenie A M-t Obbens
    11 Obbens
  5. Richard M Steingart
    110 Steingart
  6. Howard T Thaler
    190 Thaler