title: Caffeine as an adjuvant therapy to opioids in cancer pain: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Opioid therapy often shows insufficient efficacy and substantial adverse events in patients with advanced cancer.
  
  
  OBJECTIVE
  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 (200mg) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Dongguk University, Seoul, Korea; Department of Family Medicine, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Korea. Electronic address: lisasuhmd@hotmail.com.
authors.forename: Sang-Yeon
authors.initials: SY
authors.lastname: Suh
authors.forename: Youn Seon
authors.initials: YS
authors.lastname: Choi
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
authors.forename: Young Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Cho
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Bae
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ah-Ram
authors.initials: AR
authors.lastname: Seo
authors.forename: Hong-Yup
authors.initials: HY
authors.lastname: Ahn
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D010166:Palliative Care / Q000379:methods*; D015990:Placebo Effect; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: Caffeine; cancer pain; opioid therapy; randomized controlled trial