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Efficacy of low-dose and/or adjuvant methadone in palliative medicine
  1. Cameron Chalker1,
  2. Hannah O'Neill1 and
  3. Faith Cranfield2,3
  1. 1 Department of Medicine, Royal College of Surgeons in Ireland School of Medicine, Dublin, Ireland
  2. 2 Saint Francis Hospice Blanchardstown, Dublin, Ireland
  3. 3 Connolly Hospital Blanchardstown, Dublin, Ireland
  1. Correspondence to Cameron Chalker, Royal College of Surgeons in Ireland School of Medicine, Dublin D02 YN77, Ireland; cameronchalker{at}


Objectives To summarise the current body of published evidence on the use of low-dose and/or adjuvant methadone in the palliative care setting.

Methods The authors searched multiple databases (PubMED, SCORPUS, EMBASE and the Cochrane library) for relevant articles using the terms ‘methadone’, ‘palliative’, ‘low dose’ and ‘adjuvant’. The review was restricted to articles published between 2003 and 2018. Paediatric and single-case studies were also excluded. Evidence quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.

Results Our search yielded 171 results, of which seven met the inclusion criteria. Four were retrospective chart reviews, one was a retrospective cohort study, one was a case series and one was a double-blind randomised control trial. The overall quality was found to be very low. Of the seven articles, all seven reported some improvement in pain with the addition of low-dose or adjuvant methadone. This improvement was statistically significant in four out of seven articles; statistical significance was not commented on in the remaining three articles.

Conclusion While case series and chart reviews offer promising results about the utility of adjuvant and/or low-dose methadone in the management of complex pain, the very low evidence quality, relative dearth of studies and near absence of randomised controlled trials make it impossible to draw firm conclusions. Thus, while very preliminary evidence suggests methadone is a potentially effective and valuable agent, further research must be performed before such findings can be implemented into clinical practice.

  • cancer
  • hospice care
  • hospital care
  • pain
  • pharmacology

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  • Contributors CC and HON determined the inclusion/exclusion criteria, performed the literature search, reviewed publications and drafted the report. Figure design by HON. Revisions by CC. FC conceptualised this review and provided essential mentorship and guidance.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.