title: A systematic review of combination step III opioid therapy in cancer pain: an EPCRC opioid guideline project.
abstract: BACKGROUND
  The use of combinations of opioids is a common clinical practice; however, this is not advocated by the World Health Organization (WHO) analgesic ladder. As opioid combination therapy becomes used increasingly, a review of the evidence on this practice was conducted.
  
  
  OBJECTIVE
  To carry out a systematic review of the use of strong opioids in combination in cancer pain.
  
  
  METHODS
  The following databases were searched electronically: Embase (1980-2010 week 2), Medline (1950-2010 week 1) and the Cochrane Database of Systematic Reviews (fourth quarter 2009). Only strong opioids as defined by the WHO ladder and full opioid agonists were examined. Only studies conducted in human, adult patients with chronic cancer pain were eligible. Studies must have contained data on efficacy and/or side effects in the key point. Appraisal was conducted using predetermined criteria set by the EAPC guideline development group. All potential papers were reviewed independently by both authors.
  
  
  RESULTS
  In total 596 articles were retrieved resulting in only two eligible studies, which were rated as grade C and grade D evidence. These examined morphine in combination with oxycodone or fentanyl/methadone.
  
  
  CONCLUSIONS
  Only a weak recommendation can be used to support combination opioid therapy. This recommendation is also based on the caveat that the desirable effects of combination opioid therapy is outweighed by any disadvantages that this would confer. Prospective randomized trials are needed to clarify the benefits and safety of combination opioid therapy.
authors.affiliation: University of Edinburgh, UK. marie.fallon@ed.ac.uk
authors.forename: Marie T
authors.initials: MT
authors.lastname: Fallon
authors.forename: Barry J A
authors.initials: BJ
authors.lastname: Laird
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005060:Europe; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017410:Practice Guidelines as Topic
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations