title: A phase III randomized, double-blind, placebo-controlled study evaluating dextromethorphan plus slow-release morphine for chronic cancer pain relief in terminally ill patients.
abstract: This multicenter trial examined the efficacy and safety of dextromethorphan (DM) as an enhancer of analgesia and modulator of opioid tolerance in cancer patients with pain. Eligible patients were randomized to slow-release morphine plus DM or slow-release morphine plus placebo. The initial DM dose was 60 mg four times daily for seven days, with an increase to 120 mg four times daily, if tolerated, for another seven days. During the study, patients recorded medications and scores for pain, nausea, drowsiness, and insomnia. Sixty-five patients were randomized. Although average pain scores (12.6 vs. 15.8), number of breakthrough doses (9 vs. 11.3), and change in total morphine consumption (550.9 mg vs. 597.1mg) were less in the DM group than placebo group, the differences were not statistically significant (P=0.31-0.33). Side-effect scores were not statistically significantly different. Dizziness was greater in the DM (58%) than placebo (36%) group. This study showed a statistically nonsignificant enhancement of analgesia or modulation of opioid tolerance in cancer patients with pain when DM was added to morphine. Participants receiving the DM also had more toxicity, particularly dizziness. This toxicity and the limited evidence of effect do not support the use of DM to enhance opioid analgesia or to modulate opioid tolerance in cancer patients.
authors.affiliation: Palliative Care Medicine, Queen's University, Kingston, Ontario, Canada. dudgeond@kgh.kari.net
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Dudgeon
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
authors.forename: Bruno
authors.initials: B
authors.lastname: Gagnon
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Watanabe
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Allan
authors.forename: David G
authors.initials: DG
authors.lastname: Warr
authors.forename: Susan M
authors.initials: SM
authors.lastname: MacDonald
authors.forename: Colleen
authors.initials: C
authors.lastname: Savage
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Pater
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications*; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D013727:Terminal Care
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D003915:Dextromethorphan; D009020:Morphine