Tassinari, D., Sartori, S., Tamburini, E., Scarpi, E., Tombesi, P., Santelmo, C., & Maltoni, M. (2009). Transdermal fentanyl as a front-line approach to moderate-severe pain: A meta-analysis of randomized clinical trials. Journal of Palliative Care, 25, 172–180.

To compare transdermal fentanyl to slow-release oral morphine—in terms of safety, efficacy, and patient compliance—in patients who have stable opiate requirements for pain control

• Databases searched were MEDLINE and EMBASE (January 1966–June 2007).
• Search keywords were Medical Subject Headings (MeSH) terms for cutaneous administration, oral administration, analgesic opioid administration and dosage/adverse effects, delayed action preparations, fentanyl, cancer pain, drug therapy, low back pain/drug therapy and morphine administration, dosage, and adverse effects.
• Studies were included in the review if they
  • Were randomized controlled trials.
  • Reported mature phase III trial data.
• Studies were excluded if they were nonrandomized trials.

Of the 117 trials retrieved, 11 were considered potentially eligible. The analysis included five trials. Three trials included patients with cancer, and two included patients without cancer. The quality of the reports was evaluated using the Jadad scale.

• The studies reported on a total sample of 1,309 patients across all trials.
• The sample included 652 patients who were treated with transdermal fentanyl and 657 who were treated with slow-release oral morphine.
• The sample included 373 patients who were treated for cancer pain.
• In some trials, patients were in palliative care programs.

• Compared to slow-release oral morphine, transdermal fentanyl was associated with less constipation, urinary retention, and laxative use, as well as higher patient preference.
• Slow-release oral morphine was associated with less nausea, diarrhea, and sweating.
• Authors observed no significant differences between the two drugs in regard to overall safety or gastrointestinal safety, somnolence, anorexia, vomiting, hypoventilation, insomnia, or uncontrolled pain that called for opiate rescue doses.
• Findings were stable following analysis of cancer and noncancer subgroups.

Side-effect profiles of transdermal fentanyl and oral slow-release morphine differ, but in this analysis authors observed no significant differences in overall side effects and patient preference regarding the two approaches. Transdermal fentanyl appears to be a valid alternative to oral opiates.

• The analysis included a small number of studies.
• Two trials included in this evaluation were of low quality.
• Not all trials used the same methods of equianalgesia.

Findings should be interpreted with caution, given the limitations of this meta-analysis. Additional research comparing transdermal and other medication delivery routes for pain control is warranted. Transdermal opiates may be particularly useful for patients using opiate switching. Addressing individual patients' needs and concerns may mean that side-effect profiles play an important role in the selection of a medication delivery route.