A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes

J Pain Symptom Manage. 2014 Apr;47(4):772-785.e5. doi: 10.1016/j.jpainsymman.2013.05.020. Epub 2013 Aug 24.


Context: With many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs.

Objectives: To identify all the evidence and assess the relative clinical value of currently approved BTCP medications.

Methods: Following a systematic literature search (2007-2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication.

Results: INFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes.

Conclusion: From current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine.

Keywords: Analgesia; breakthrough cancer pain; fentanyl; morphine; network meta-analysis; randomized controlled trial.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / therapeutic use*
  • Breakthrough Pain / drug therapy*
  • Breakthrough Pain / physiopathology*
  • Humans
  • Neoplasms / physiopathology*
  • Randomized Controlled Trials as Topic


  • Analgesics, Opioid