Objective: Review and analyze the evidence base comprising methadone conversion methods and associated dosing ratios for the treatment of pain.
Design: Systematic review.
Methods: Clinical trials and retrospective analyses, case series, and case reports of human subjects published in the English language between January 1966 and June 2006 were included; review articles and reports with incomplete opioid data were excluded. Scatterplots displayed the relationship between previous morphine dose and final methadone dose and dose ratio. Correlation analyses were conducted using Pearson's and Spearman's correlation coefficient with a one-tailed test of significance.
Results: Twenty-two clinical studies and 19 case reports or series were reviewed (N = 730 patients). Methadone rotations were most common in cancer patients (N = 625, 88.9%) and those prescribed morphine (N = 259 patients, 41.7% of rotations where prerotation opioid was identified [N = 621]) or hydromorphone (N = 234 patients, 37.7% of rotations). In clinical studies, the most common reason for switching to methadone was a combination of inadequate analgesia and adverse effects (N = 254, 38.6%). Despite various approaches, 46-89% of rotations were successful. Overall, there was a relatively strong, positive correlation between the previous morphine dose and the final methadone dose and dose ratio, but ratios varied widely.
Conclusions: There was no evidence to support the superiority of one method of rotation to methadone over another. Patients may be successfully rotated to methadone despite discrepancies between rotation ratios initially used and those associated with stabilization. Further research is needed to identify patient-level factors that may explain the wide variance in successful methadone rotations.