title: A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.
abstract: Guidelines for opioid treatment of chronic non-malignant pain recommend long-acting over short-acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double-blind, double-dummy, 8-week comparison of long-acting dihydrocodeine tablets (DHC-Continus) with short-acting dihydrocodeine tablets in 60 patients with chronic non-malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine-paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11-point numerical rating scale in a 7-day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health-related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long-acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long-acting opioids.
authors.affiliation: National Competence Centre for Complex Symptom Disorders, Trondheim, Norway Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Department of Internal Medicine, Sørlandet Hospital HF, Kristiansand, Norway Department of Pain and Complex Symptom Disorders, St. Olav's University Hospital, Trondheim, Norway Department of Pain Management and Research, Oslo University Hospital, University of Oslo, Oslo, Norway Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Line
authors.initials: L
authors.lastname: Pedersen
authors.forename: Petter Christian
authors.initials: PC
authors.lastname: Borchgrevink
authors.forename: Harald Petter
authors.initials: HP
authors.lastname: Breivik
authors.forename: Olav Magnus Søndenå
authors.initials: OMS
authors.lastname: Fredheim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D003061:Codeine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; C014481:dihydrocodeine; D003061:Codeine
keywords: Chronic non-malignant pain; Dihydrocodeine; Long-acting opioids; Randomized controlled trial; Short-acting opioids