Rivera, I.V., Garrido, J.C.M., Velasco, P.G., de Enciso, I.E.X., & Clavarana, L.V. (2014). Efficacy of sublingual fentanyl vs. oral morphine for cancer-related breakthrough pain. Advances in Therapy, 31, 107–117. 

To determine the efficacy, tolerability, and patient satisfaction with treatment for breakthrough pain with sublingual fentanyl citrate and oral morphine

Patients were allocated consecutively to receive either oral morphine or sublingual fentanyl. Doses were adjusted individually until an effective dose was obtained. Effective dose was defined as the dose needed to achieve a 50% pain reduction in each breakthrough episode. Patients maintained a pain diary. Side effects were assessed by a physician who was blinded to group allocations in each visit. Outcomes were assessed at three, seven, 15, and 30 days.

• N = 40
• MEAN AGE = 65.6 years
• MALE: 57%, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving fentanyl, oxycodone-naloxone, hydromorphone, or tapentadol for chronic pain.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Spain

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Prospective, double-blinded, two-group trial

• Pain intensity on a 0–10 Visual Analog Scale (VAS)
• Frequency of breakthrough episodes and onset of relief from diaries
• Time required for dose titration
• Questionnaire for adverse effects

Mean pain intensity was consistently lower for those receiving sublingual fentanyl at all time points (p < 0.0001). Sublingual fentanyl gave faster relief onset at all time points with an average of 5–8.5 minutes for fentanyl compared to 15–23 minutes for oral morphine (p < 0.001). The titration period for fentanyl was a mean of 6.6 days compared to 13.3 days for oral morphine (p < 0.001). No patients treated with fentanyl were dissatisfied with treatment compared to 37.5% of those receiving oral morphine who were dissatisfied or very dissatisfied. There were no significant differences in side effects, and the side effects reported were typical of those seen with opioid medications.

The findings of this study showed that compared to oral morphine, sublingual fentanyl citrate had a faster onset and was associated with greater reductions in pain intensity for episodes of breakthrough pain in patients with cancer. It took less time to titrate to an effective dose with sublingual fentanyl.

• Small sample (< 100)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: The exact methods of measurement of satisfaction were not clear. There was no discussion of any missing data from patient diaries, and the reliability of diary data alone may be questionable.

Sublingual fentanyl was more effective than oral morphine for breakthrough pain in terms of faster onset and greater reduction in pain intensity. In this study, it also was quicker to titrate to the effective dosage with sublingual fentanyl. This study added to the growing body of evidence suggesting superior results with transmucosal opioids for breakthrough pain. Effective pain control is a critical aspect of care for patients with cancer, and the goal in the management of breakthrough pain episodes is the achievement of rapid relief, including the length of time it takes to titrate doses and the length of time for onset of relief. Nurses need to advocate for the most effective interventions to manage breakthrough pain for their patients.