BACKGROUND
Fatigue is common in multiple sclerosis (MS) and adversely affects function and quality of life. We examined clinical correlates of fatigue, its relationship with depression and sleepiness, and whether fatigue-related medications improve patient-reported outcomes.
MATERIAL AND METHODS
This single-center, longitudinal observational study retrospectively analyzed prospectively collected data from 203 veterans, categorized based on the presence or absence of fatigue. Primary outcomes were changes in the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Epworth Sleepiness Scale (ESS) from baseline to 12 months. Secondary outcomes included changes in the EuroQol 5-Dimension Questionnaire (EQ-5D), EQ visual analog scale (EQ-VAS), Total Functional Independence Measure (TFIM), Expanded Disability Status Scale (EDSS), 2-Minute Walk Test (2MWT), and Beck Depression Inventory (BDI). Medication exposure (amantadine, modafinil/armodafinil, methylphenidate/dextroamphetamine) was recorded.
RESULTS
Fatigue was present in 134 of 203 (66%) and associated with higher body mass index (30.1±5.5), hyperlipidemia (53.7%), diabetes (16.4%), higher BDI (4.58±4.36) and ESS (10.7±6.51), and worse EQ-5D VAS (all P<0.01). Strong positive correlations were observed among fatigue (FSS/MFIS), depression (BDI), sleepiness (ESS), and disability (EDSS) scales (P<0.05). Compared with no medication, fatigue-related medications did not improve FSS/MFIS or EQ-VAS scores; however, modest gains favored treated patients in TFIM change (P=0.04) and 2MWT distance (P=0.02). Post hoc comparisons across amantadine, modafinil/armodafinil, and amphetamine showed no between-drug differences in primary or secondary outcomes.
CONCLUSIONS
MS fatigue in veterans is highly prevalent and closely linked to metabolic comorbidities, depression, and sleep disturbance. Common fatigue medications provided no improvement in fatigue severity and quality of life.

Keywords: Multiple Sclerosis; Veterans; Fatigue; Sleep; Depression; Quality Improvement