Transdermal fentanyl as a front-line approach to moderate-severe pain: A meta-analysis of randomized clinical trials

Objective: The safety of transdermal fentanyl (TF) in comparison with slow-release oral morphine (SROM) in moderate-severe pain was assessed. Design: A systematic review of the literature was performed to identify all randomized trials comparing TF and SROM in moderate-severe pain. Overall safety was the primary end point. Trials enrolling both cancer and non-cancer patients were included in the analysis. Heterogeneity was assessed using the Mantel-Haenszel test; a random effects model was used for the pooled analysis. Cumulative and distinctive analyses for cancer and non-cancer pain were performed whenever the outcome was reported in at least two trials. Results: Five trials met the inclusion criteria. A significant advantage of TF was documented for constipation, laxative use, and urinary retention. TF was preferred by cancer and non-cancer patients. A difference in favour of SROM was documented for nausea, diarrhea, and sweating in cancer and non-cancer patients. No differences were observed for the other items considered. Conclusions: TF and SROM seem to have a different side effects profile, and TF seems to be preferred by patients. The hierarchical approach traditionally recommended by the main scientific societies (oral morphine and then TF) could be replaced by a front-line approach based on patients' characteristics and needs.