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.

Keywords: BEYOND study; Clinical trial; Depression; Glatiramer acetate; Interferon beta; Multiple sclerosis.

Fig. 1

Number of patients with BDI-II scores at selected time points stratified by BDI-II score at screening and treatment assignment. Fisher’s exact test was used for comparison

Fig. 2

Proportion of patients with a BDI scores ≤13 at screening who had BDI-II scores of ≥14 at the end of the study (n = 794); b BDI-II scores ≥14 at screening who had BDI-II scores ≤13 at the end of the study (n = 794). Fisher’s exact test was used for comparison

Fig. 3

Proportion of patients in whom depression was reported as an adverse event at any given time during the study (n = 2220). Fisher’s exact test used for comparison