Opioids for the management of breakthrough (episodic) pain in cancer patients

Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004311. doi: 10.1002/14651858.CD004311.pub2.


Background: Breakthrough pain is a transient increase in pain intensity over background pain. It is a common and distinct component of cancer pain that can have a negative impact for both the patient and carers' quality of life. Breakthrough pain is usually related to background pain and is typically of rapid onset, severe in intensity, and generally self-limiting with an average duration of 30 minutes. At present the current approach to managing breakthrough pain is using supplemental analgesia (also known as rescue medication) at a dose proportional to the total around-the-clock (ATC) opioid dose.

Objectives: This review explores and assesses the evidence for the use of opioids in the management of breakthrough pain in patients with cancer.

Search strategy: MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CancerLit (1993 to 2005), CINAHL (1982 to 2005) and Cochrane databases were searched. Handsearching of medical journals and reference from key textbooks was undertaken and drug companies contacted for unpublished data. There was no language restriction. Date of most recent search: January 2005.

Selection criteria: Randomized controlled trials of opioids used as rescue medication against active or placebo comparator in patients with cancer pain were included. Outcome measures sought were reduction in pain intensity measured by an appropriate scale, adverse effects, attrition, patient satisfaction and quality of life. There were no language restrictions.

Data collection and analysis: Eligible studies were selected and examined independently by the two reviewers. Full text was retrieved if any uncertainty about eligibility remained. Non-English texts were screened. 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: Four studies (393 participants) met the inclusion criteria, all were concerned with the use of oral transmucosal fentanyl citrate (OTFC) in the management of breakthrough pain. Two studies examined the titration of OTFC, one study compared OTFC to normal release morphine and one study compared OTFC to placebo.OTFC was shown to be an effective treatment for breakthrough pain. When compared to placebo and morphine, participants gave lower pain intensity scores and higher pain relief scores for OTFC at all time points. Global assessment scores also favoured OTFC.

Authors' conclusions: There is evidence that OTFC is an effective treatment in the management of breakthrough pain. The randomised trial literature for the management of breakthrough pain is small and no trials were found for other opioids. Given the importance of this subject, more trials need to be undertaken.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Fentanyl / administration & dosage
  • Fentanyl / therapeutic use*
  • Humans
  • Morphine / therapeutic use
  • Neoplasms / complications*
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain Measurement
  • Randomized Controlled Trials as Topic


  • Analgesics, Opioid
  • Morphine
  • Fentanyl