The quality of evidence is downgraded by study limitations (unclear allocation concealment and lack of blinding), and by imprecise results (few patients).
A Cochrane review [Abstract] 1 included 6 studies with a total of 388 subjects. All studies were of adult participants with various types of cancer who required strong opioids to control their pain. Meta-analysis was not performed due to differences in the included studies. Four studies compared oral methadone to oral morphine, 1 study compared oral methadone to oral morphine or transdermal fentanyl patch, and 1 study compared oral or intramuscular methadone to oral or intramuscular morphine.
There were no clear differences in participant-reported pain intensity or pain relief between methadone and morphine or transdermal fentanyl: similar proportions of participants were able to tolerate each drug and achieve a level of pain that was probably similar to mild pain. One study (n=103) reported > 20% improvement in pain scores for 76% of morphine and 75% methadone participants. One study (n=54) reported all achieved no worse than mild pain (pain score of 3/10 or less after treatment) based on mean pain scores. Two studies (n=148) reported mean pain scores very close to a score of 3. Adverse events were typical for opioids (e.g. sedation, somnolence, dry mouth, constipation) but inconsistently reported. Included studies were underpowered to investigate serious adverse events, including arrhythmias.
Methadone has complex pharmacokinetics and high potential for accumulation leading to delayed toxicity. If other opioids are not tolerated it may have a role, providing the issues of dose titration and possible severe adverse effects are considered.
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