Israel, F.J., Parker, G., Charles, M., & Reymond, L. (2010). Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients requiring high-dose strong opioids: A randomized, double-blind, placebo-controlled, crossover trial. Journal of Pain and Symptom Management, 39, 548–554.

To investigate potential analgesic benefits of 4 g paracetamol daily for palliative patients with cancer requiring high-dose opioids

Patients received usual medications plus 4 g paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numeric rating scale ranging from 0 (no pain) to 10 (unbearable pain) and recording numbers of breakthrough analgesics. Patients also indicated in which part of the study their pain was better controlled.

• The study reported on 22 patients who completed the study.
• Mean patient age was 56.3 years (range = 28–79 years).
• The sample was 55% male and 45% female.
• Patients had a variety of cancer types.
• Baseline pain score was greater than or equal to 2, and patients were using at least 200 mg daily morphine equivalents.

• Multisite
• Both inpatient and community-based patients from Brisbane South Palliative Care Service and Mt. Olivet Palliative Care Service in Brisbane, Australia

The study used a randomized, double-blind, placebo-controlled, crossover design.

• Numeric rating scale (0–10)
• Patient-generated daily diary
• Mini-Mental State Examination

There were no significant order or treatment-by-the-order interaction effects for any variable. There were no significant differences in pain when assessed with placebo compared with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain.

Data from this study do not support the common practice of adding regular paracetamol (acetaminophen) daily to high-dose opioids to enhance pain control in the palliative setting.

The study had a small sample, with less than 30 participants.

There is a growing body of evidence suggesting that some patients do not receive any additional benefit from adding paracetamol or acetaminophen to strong or high-dose opioids. Pain management interventions should be individualized. Unwarranted exposure to potential side effects/toxicities and costs should be avoided when possible by eliminating paracetamol or acetaminophen in those individuals in whom no benefit has been demonstrated.