title: Incidence and course of depression in multiple sclerosis in the multinational BEYOND trial.
abstract: Early experience in MS generated concerns that interferon beta treatment might provoke onset or worsening of depression. The objective of the study was to compare depression incidence in relapsing-remitting MS patients receiving interferon beta-1b (IFNB-1b) or glatiramer acetate (GA) in the BEYOND trial. 891/897 (99 %) of English, French, Spanish and Italian speakers among 2244 patients randomized (2:2:1) to receive either IFNB-1b 500 µg, 250 µg, or GA 20 mg QD for 2-3.5 years submitted Beck Depression Inventory Second Edition (BDI-II) scores at screening and serially thereafter, in which scores ≥14 indicated depression. Baseline BDI-II scores ≥14 were reported in 232/891 patients (26.3 %), with no meaningful difference among the three treatment arms noted at this or at any other time during the study including trial end. Percentages of patients depressed by BDI-II scores deviated little in any arm at any time (IFNB-1b 500 µg: 24.7 %, IFNB-1b 250 µg: 24.4 %, GA: 32.4 %). Antidepressant usage was likewise similar among the three treatment arms (IFNB-1b 500 µg: 33.7 %, IFNB-1b 250 µg: 31.8 %, GA: 28.8 %) as was depression severity and the frequency with which non-blinded treating physicians recorded depression as an adverse event (IFNB-1b 500 µg: 17.2 %, IFNB-1b 250 µg: 17.0 %, GA: 14.4 %). Treating physicians attributed depression to IFNB-1b 250 µg therapy in 53.6 % and to GA in 21.9 % of instances. This large, prospective, randomized-controlled MS dataset showed no increased risk of depression above baseline values with standard or double-dose IFNB-1b or GA QD treatment.
authors.affiliation: Department of Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Medical Center Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland. sven.schippling@usz.ch.
authors.forename: Sven
authors.initials: S
authors.lastname: Schippling
authors.affiliation: St. Michael's Hospital, Toronto, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, USA.|Department of Neurology, Medical Faculty, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Knappertz
authors.affiliation: Bayer HealthCare AG/Bayer Pharma AG, Berlin, Germany.|University Hospital Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pohl
authors.affiliation: Bayer HealthCare AG/Bayer Pharma AG, Berlin, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Bogumil
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Suarez
authors.affiliation: Rutgers-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Cook
authors.affiliation: Ospedale San Raffaele, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Vita-Salute University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Piedmont Health Care, Mooresville, NC, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Jeffery
authors.affiliation: Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Arnason
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D000068556:Interferon beta-1a / Q000627:therapeutic use; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology* / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D013405:Suicide / Q000523:psychology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000928:Antidepressive Agents; D000068717:Glatiramer Acetate; D000068556:Interferon beta-1a
keywords: BEYOND study; Clinical trial; Depression; Glatiramer acetate; Interferon beta; Multiple sclerosis