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.
authors.affiliation: Pain and Palliative Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York; Weil Cornell Medical College, New York, New York.
authors.forename: Natalie
authors.initials: N
authors.lastname: Moryl
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tamasdan
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Dana
authors.initials: D
authors.lastname: Tarcatu
authors.affiliation: Epidemiology and Biostatistics Department, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Howard T
authors.initials: HT
authors.lastname: Thaler
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Denise
authors.initials: D
authors.lastname: Correa
authors.affiliation: FACC, Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Steingart
authors.affiliation: Pain and Palliative Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Payne
authors.affiliation: Pain and Palliative Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York; Weil Cornell Medical College, New York, New York.
authors.forename: Eugenie
authors.initials: E
authors.lastname: Obbens
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D006801:Humans; D008691:Methadone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone