Methadone for cancer pain

Methadone is an opioid used in the management of cancer pain. A particular role in neuropathic pain has been suggested. The quest for evidence based palliative care prompted a formal appraisal of methadone in comparison with other analgesics. This is an updated version of the original Cochrane review published in Issue 1, 2004.

To determine effectiveness and safety of methadone analgesia in cancer pain patients.

MEDLINE, EMBASE, CancerLit, CINAHL and Cochrane databases were searched in 2002 using a strategy developed with the Cochrane Pain, Palliative and Supportive Care Group. Repeat searches were conducted in September 2006.

Randomised controlled trials (RCTs) of methadone against active or placebo comparator in patients with cancer pain were included. Outcome measures sought were reduction in pain intensity, adverse effects, attrition, patient satisfaction and quality of life. There were no language restrictions.

Eligible studies were selected with independent collaboration from a colleague. Full text was retrieved if any uncertainty about eligibility remained. Non-English texts were screened by Cochrane contacts. Quality assessment and data extraction were conducted using standardised data forms. Drug and placebo dose, titration, route and formulation were compared and detail of all outcome measures (if available) recorded.

This updated review includes nine RCTs (six double blinded, two crossover) with 459 recruits and 392 completing patients. All studies involved active opioid comparators (morphine, dextromoramide, pethidine, diamorphine with cocaine mixture) with different dose and titration schedules and various pain scoring scales. One study differentiated cases by pain syndrome. Few presented complete pain data sets but complete adverse events data were recorded in every study. Efficacy and tolerability were broadly similar between methadone and morphine. No useful meta-analysis has been possible.

The updated review contains new information supporting the previous conclusions that methadone has similar analgesic efficacy to morphine. The additional study examined neuropathic and non-neuropathic pain, finding no superiority for methadone in the former group. The new study also addresses a clinically relevant concern about short term/single dose studies. Use beyond a few days may result in methadone accumulation leading to delayed onset of adverse effects. In an assessment over 28 days there was a higher rate of withdrawal due to side effects in the methadone group. This observation reinforces the advice that experienced clinicians should take responsibility for initiation and careful dose adjustment and monitoring of methadone.