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

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.