Use of Symptomatic Drug Treatment for Fatigue in Multiple Sclerosis and Patterns of Work Loss

To describe the use of central stimulants and amantadine for fatigue in MS and evaluate a potential association with reduced work loss in people with MS.

We conducted a nationwide, matched, register-based cohort study in Sweden (2006 to 2023) using national registers with prospective data collection. We included individuals with MS, identified via the Swedish MS register or ≥ 3 MS diagnoses in the National Patient Register, who initiated treatment with modafinil, amantadine, or central stimulants for ADHD (ADHD-Drugs), along with untreated individuals matched on modafinil start date, age, sex, time since MS diagnosis, and prior-year work loss. The main outcome was monthly work loss, defined as the sum of net days on sick leave, disability pension, and activity compensation.

We identified 2162 new modafinil users, 462 amantadine, 424 ADHD drugs, and 9762 untreated. All cohorts showed increasing work loss before index, followed by no change in work loss over the subsequent 24 months. Modafinil users had a significantly greater attenuation, but with low effect size, of the increasing trajectory of average monthly work loss than untreated (-0.17 days; 95% CI: -0.22, -0.12), with no significant differences between modafinil and other treated groups. Modafinil was the most prescribed treatment, with 1-year prevalence of 8.5% in 2006 and 7% in 2023.

A potential minor treatment benefit is suggested by the statistically significant, small attenuation of worsening work loss following fatigue treatment initiation compared with untreated people with MS. No differences in treatment benefit were observed across fatigue treatments.