title: Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial.
abstract: Fibromyalgia is a syndrome characterized by chronic widespread pain and associated with sleep disturbance, depression, fatigue, and cognitive dysfunction. Polypharmacy is commonly used, but supportive evidence is limited. Most fibromyalgia trials focus primarily on pain reduction with monotherapy. This trial compares a pregabalin-duloxetine combination to each monotherapy. Using a randomized, double-blind, 4-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine, and pregabalin-duloxetine combination-for 6 weeks. Primary outcome was daily pain (0-10); secondary outcomes included global pain relief, Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. Of 41 participants randomized, 39 completed ≥2 treatments. Daily pain during placebo, pregabalin, duloxetine, and combination was 5.1, 5.0, 4.1, and 3.7, respectively (P < 0.05 only for combination vs placebo, and pregabalin). Participants (%) reporting ≥moderate global pain relief were 18%, 39%, 42%, and 68%, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Fibromyalgia Impact Questionnaire scores were 42.9, 37.4, 36.0, and 29.8, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). SF-36 scores were 50.2, 55.7, 56.0, and 61.2, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Medical Outcomes Study Sleep Scale scores were 48.9, 35.2, 46.1, and 32.1, respectively (P < 0.05 only for combination vs placebo, and duloxetine). BDI-II scores were 11.9, 9.9, 10.7, and 8.9, respectively (P < 0.05 only for combination vs placebo). Moderate-severe drowsiness was more frequent during combination vs placebo. Combining pregabalin and duloxetine for fibromyalgia improves multiple clinical outcomes vs monotherapy. Continued research should compare this and other combinations to monotherapy for fibromyalgia.
authors.affiliation: Departments of aAnesthesiology and Perioperative Medicine and bBiomedical and Molecular Sciences, Queen's University, Kingston, Canada cUniversity of Toronto, Department of Anesthesia, University of Toronto, Toronto, Canada dPublic Health Sciences eMathematics and Statistics fPsychology and gPsychiatry, Queen's University, Kingston, Canada hDivision of Rheumatology, Department of Medicine Queen's University, Kingston, ON, Canada iDepartment of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Gilron
authors.forename: Luis E
authors.initials: LE
authors.lastname: Chaparro
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Holden
authors.forename: Roumen
authors.initials: R
authors.lastname: Milev
authors.forename: Tanveer
authors.initials: T
authors.lastname: Towheed
authors.forename: Deborah
authors.initials: D
authors.lastname: DuMerton-Shore
authors.forename: Sarah
authors.initials: S
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride / Q000627:therapeutic use*; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management; D010147:Pain Measurement; D000069583:Pregabalin / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D000068736:Duloxetine Hydrochloride