Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature

J Palliat Med. 2008 Apr;11(3):492-501. doi: 10.1089/jpm.2007.0200.


Background: To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine.

Methods: A systematic review of the literature in the MEDLINE and EMBASE databases from 1966 to June 2007 was independently performed by two authors. All phase 3 randomized trials comparing transdermal opiates and slow-release oral morphine in the treatment of moderate-severe cancer pain were considered eligible and included in the analysis. The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal. Heterogeneity was analyzed using the Mantel-Haenszel test, and outcome analysis was performed using a random effect model; an alpha error lower than 5% was assumed as statistically significant.

Results: Four trials met the selection criteria. The safety of transdermal opiates (fentanyl and buprenorphine) and slow-release oral morphine was analyzed in 425 patients. A significant difference in favor of transdermal opiates was observed for constipation (OR=0.38, p<0.001), and patients' preference (OR=0.43, p=0.014, in the three trials investigating transdermal fentanyl). No significant differences were observed for overall adverse effects, overall gastrointestinal adverse effects, overall neurologic adverse effects, nausea, somnolence, hypoventilation, trial withdrawal, and changes in opiate treatments.

Conclusion: Although no difference in the overall adverse effect profile exists between transdermal opiates and slow release oral morphine, the difference in some adverse effects (mainly constipation) seems to favor transdermal opiates in the preference of patients with moderate-severe cancer pain.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects*
  • Buprenorphine / administration & dosage
  • Buprenorphine / adverse effects
  • Delayed-Action Preparations
  • Fentanyl / administration & dosage
  • Fentanyl / adverse effects
  • Humans
  • Morphine / administration & dosage*
  • Morphine / adverse effects*
  • Neoplasms / complications*
  • Pain / drug therapy*
  • Pain / etiology
  • Randomized Controlled Trials as Topic


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Buprenorphine
  • Morphine
  • Fentanyl