Caffeine as an adjuvant therapy to opioids in cancer pain: A randomized, double-blind, placebo-controlled trial

Sang Yeon Suh, Youn Seon Choi, Sang Cheul Oh, Young Sung Kim, Kyunghee Cho, Woo Kyung Bae, Ju Hyun Lee, Ah Ram Seo, Hong Yup Ahn

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Context: Opioid therapy often shows insufficient efficacy and substantial adverse events in patients with advanced cancer. Objectives: To assess the efficacy of caffeine infusion as an adjuvant analgesic to opioid therapy in patients with advanced cancer. Methods: A double-blind, randomized, placebo-controlled trial was conducted in the palliative care wards of two teaching hospitals in South Korea. A total of 20 of 41 participants were assigned to the caffeine group and 21 to the placebo group. The participants received caffeine (200 mg) or normal saline intravenously once a day for two days. The primary outcome was pain, which was measured using a 10-point rating scale. Other outcomes included drowsiness, confusion, nausea, sleep disturbance, fatigue, and sadness. Results: Three participants (two in the caffeine group and one in the placebo group) dropped out after the first intervention because of insomnia; thus, 38 participants completed the trial. Pain score was significantly lower in the caffeine group than in the placebo group after the second trial (P = 0.038). The mean reduction in pain intensity in the caffeine group was 0.833 (95% confidence interval [CI] 0.601-1.066), whereas that in the placebo group was 0.350 (95% CI 0.168-0.532). Considering an improvement higher than 30% from baseline as the threshold value, drowsiness improved significantly in the caffeine group after the first trial (P = 0.041). Adverse event rate did not differ between the two groups. Conclusion: Caffeine infusion significantly reduced pain and drowsiness, but the reduction did not reach clinical significance in patients with advanced cancer undergoing opioid therapy. Further investigations are warranted.

Original languageEnglish
Pages (from-to)474-482
Number of pages9
JournalJournal of Pain and Symptom Management
Issue number4
Publication statusPublished - 2013 Oct


  • Caffeine
  • cancer pain
  • opioid therapy
  • randomized controlled trial

ASJC Scopus subject areas

  • Nursing(all)
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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