Tassinari, D., Sartori, S., Tamburini, E., Scarpi, E., Raffaeli, W., Tombesi, P., & Maltoni, M. (2008). 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. Journal of Palliative Medicine, 11(3), 492–501.

To compare the safety profiles, adverse effects, and patients' preferences regarding slow-release oral morphine and transdermal opiates

• Databases searched were MEDLINE and EMBASE, January 1966–June 2006.
• Search keywords were administration, cutaneous (in subject headings); analgesic, opioid/*administration, and dosage adverse effects (in subject headings); and fentanyl, buprenorphine, cancer pain/*drug therapy (as main terms).
• Studies were included if they
  • Were randomized controlled trials at phase III.
  • Included subjects with moderate to severe cancer pain and who had a defined opiate need at study entry.
  • Compared slow-release oral morphine to transdermal opiates.
• Studies were excluded if information about randomization was inadequate, the study did not report safety data, the sample included patients who needed opiate titration at study entry, or the study used historical controls or was a phase 2 trial.

• The search retrieved 117 studies. Twelve studies were considered potentially eligible. Four were included in analysis.
• Authors evaluated study quality by means of the Jadad scale. Two of the studies were of low quality, with a Jadad score of 2 or less.

• The sample for meta-analysis consisted of four studies, which included 425 patients. Of the 425 patients, 188 were treated with transdermal fentanyl and 26 received buprenorphine.
• The range of sample size was 47–202 patients.

• Comparison of overall adverse effects showed no heterogeneity and no difference between treatments (odds ratio [OR] 0.789, p = 0.465).
• Compared to oral slow-release morphine, transdermal opiates seemed better at reducing constipation (OR = 0.38, p < 0.001). Authors noted no differences or heterogeneity in other adverse events.
• Authors analyzed adverse events overall as well as individually. Adverse events included constipation, diarrhea, anorexia, nausea, vomiting, insomnia, somnolence, confusion, headache, and vertigo.
• Patient preference data showed that patients favored transdermal opiates (OR = 0.43, P = 0.014).

Compared to slow-release oral morphine, transdermal opiates were associated with fewer cases of constipation. Patients tended to prefer transdermal opiates to slow-release formulations.

• This meta-analysis had a small sample size.
• Of the four studies in the meta-analysis, the quality of two studies was low. View findings with caution.

Compared to slow-release oral morphine, transdermal opiates appear to be associated with fewer cases of constipation; transdermal opiates may be a better alternative for pain control in patients with constipation. This review suggests that patients may prefer pain medication via the transdermal route. Clinicians should consider constipation and preference in individualizing pain management.