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Oral Methadone for Chronic Noncancer Pain: A Systematic Literature Review of Reasons for Administration, Prescription Patterns, Effectiveness, and Side Effects

Sandoval, Juan Alberto MD*; Furlan, Andrea D MD*†‡§; Mailis-Gagnon, Angela MD, MSc, FRCPC*†∥

doi: 10.1097/01.ajp.0000146165.15529.50
Original Article

Objective: To assess the indications, prescription patterns, effectiveness, and side effects of oral methadone for the treatment of chronic noncancer pain.

Methods: We conducted searches of several electronic databases, textbooks and reference lists for controlled or uncontrolled studies in humans. Effectiveness was assessed using a dichotomous classification of “meaningful” versus “nonmeaningful” outcomes.

Results: Twenty-one papers (1 small randomized trial, 13 case reports, and 7 case series) involving 545 patients with multiple noncancer pain conditions were included. In half of the patients, no specific diagnosis was reported. Methadone was administered primarily when previous opioid treatment was ineffective or produced intolerable side effects. Starting dose ranged from 0.2 to 80 mg/day and maximum dose ranged from 20 to 930 mg/day. Pain outcomes were meaningful in 59% of the patients in the uncontrolled studies. The randomized trial demonstrated a statistically significant improvement in pain for methadone (20 mg/day) compared to placebo. Side effects were considered minor.

Discussion: Oral methadone is used for various noncancer pain syndromes, at different settings and with no prescription pattern that could be identifiable. Starting, maintenance, and maximum doses showed great variability. The figure of 59% effectiveness of methadone should be interpreted very cautiously, as it seems overrated due to the poor quality of the uncontrolled studies and their tendency to report positive results. The utilization of oral methadone for noncancer pain is based on primarily uncontrolled literature. Well-designed controlled trials may provide more accurate information on the drug's efficiency in pain syndromes and in particular neuropathic pain.

From the *Comprehensive Pain Program, Toronto Western Hospital, Toronto, Ontario, Canada; †University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada; ‡Institute for Work & Health, Toronto, Ontario, Canada; §Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; and ∥Krembil Neuroscience Center, Toronto Western Hospital, Toronto, Ontario, Canada.

Received for publication November 9, 2003; revised March 5, 2004, second revision June 9, 2004; accepted August 10, 2004.

Andrea Furlan is funded by grants from the Canadian Institute of Health Research (CIHR) and by the University of Toronto Centre for Study of Pain (UTCSP).

Reprints: Angela Mailis-Gagnon, MD, MSc, FRCPC (PhysMed), Medical Director, Comprehensive Pain Program, Toronto Western Hospital, Senior Investigator, Krembil Neuroscience Center and Toronto Western Research Institute, 4F811, 399 Bathurst Street, Toronto, Ontario Canada M5T 2S8 (e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.