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Methadone for cancer pain

  • Review
  • Intervention


Anna Hobson, Cochrane Pain, Palliative & Supportive Care Group, Pain Research Unit, The Churchill Hospital, Old Road, Oxford, OX3 7LE, UK.



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.

Search methods

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.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.

Authors' conclusions

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.

Plain language summary

Using Methadone (an opioid drug) in relieving cancer pain.

Pain is a common and debilitating symptom of cancer. Methadone is an opioid drug used to treat cancer pain, and can be given by mouth as liquid, tablet or capsule, via the rectum as a suppository, or injected into the vein, muscle or under the skin. This updated review examines clinical trial evidence published up to September 2006 to determine how effectively methadone relieves cancer pain and how well tolerated this treatment is for these patients. The available evidence permits the following conclusions: methadone has a similar efficacy to morphine (an opioid drug commonly prescribed for cancer pain patients) in treating cancer pain; methadone is no more effective than morphine for cancer-related nerve related pain; and methadone has a similar side effect profile but these side effects may become more prominent with repeated dosing.