Efficacy of low-dose and/or adjuvant methadone in palliative medicine

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

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.

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.

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.