Vissers, D., Stam, W., Nolte, T., Lenre, M., & Jansen, J. (2010). Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer. Current Medical Research and Opinion, 26(5), 1037–1045.

To compare the effectiveness of oral morphine to that of rapid-onset opioids, intranasal fentanyl spray (INFS), oral transmusocal fentanyl citrate, and fentanyl buccal tablets in the management of breakthrough cancer pain (BTCP)

Databases searched were MEDLINE, EMBASE, and BIOSIS Citation Index. The search was for the period 1996–October 2007. In addition, investigators searched conference proceedings. Pre-published data regarding INFS were included.

Search keywords included the generic and brand names of opioids and combinations of generic and brand names and pain and episodic, breakthrough, transient, flare, incident, exacerbation and transitory, cancer, malignant, tumor, and neoplasia.

Studies were included if they were 

• Randomized controlled trials (RCTs)
• Involved the management of BTCP
• Studies involving adult patients with cancer, with breakthrough pain, who were being treated with opioids for the management of background pain
• Studies that measured pain intensity difference (PID) at specified time points at the start and after the start of the pain episode

The initial review was of 128 abstracts. Assessment of abstracts and full articles, according to inclusion criteria, identified six RCTs for analysis.

• The sample across all studies was composed of 594 patients.
• The range of sample sizes was 77–139 patients.
• Samples included both males and females.
• The range of mean patient age, across all studies, was 53.9 years (SD = 11.3 years) through 62 years (SD = 11.6 years).
• The range of pain intensity at baseline across studies was 5.9–6.9 (SD = 0.2) on a 10-point scale.

PID was measured at various time points across studies. Meta-analysis demonstrated that INFS provided the greatest reduction in pain within 15 minutes, with a 99% probability in all comparisons. Oral morphine was no better than placebo within the first 45 minutes of a breakthrough episode. Oral morphine was only better than placebo after 45 minutes. INFS provided better relief than did buccal fentanyl before 45 minutes and better relief than did oral transmucosal fentanyl citrate for the first 60 minutes.

Findings show that INFS provides better rapid-onset pain relief for BTCP than does oral morphine, transmucosal oral fentanyl, and buccal fentanyl tablets. Oral morphine showed the same level of pain relief as placebo for the first 30 minutes, showing that oral morphine is an inappropriate treatment for BTCP.

All studies involved an initial period in which appropriate dosing of INFS was established for each patient. Effective use of INFS necessitates determination of individualized dose.