Caffeine as an Adjuvant Therapy to Opioids in Cancer Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract 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.