title: Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness.
abstract: BACKGROUND
  Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab.
  
  
  OBJECTIVE
  To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness.
  
  
  METHODS
  Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed.
  
  
  RESULTS
  After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue.
  
  
  CONCLUSIONS
  Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.
authors.affiliation: Department of Cognitive Psychology and Methodology, University of Basel , Basel , Switzerland.
authors.forename: Iris-Katharina
authors.initials: IK
authors.lastname: Penner
authors.affiliation: BiogenIdec Sweden AB , Upplands Väsby , Sweden (formerly employed).
authors.forename: Eva Catharina
authors.initials: EC
authors.lastname: Sivertsdotter
authors.affiliation: Department of Neurology, Oslo University Hospital , Ullevål , Norway.
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Celius
authors.affiliation: Department of Neurology, Medical University of Graz , Graz , Austria.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Neurology, Copenhagen University Hospital Rigshospitalet , Copenhagen , Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Schreiber
authors.affiliation: BiogenIdec Sweden AB , Upplands Väsby , Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Berkö
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, University Hospital of Northern Sweden, Umeå University , Umeå , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
keywords: depression; fatigue; multiple sclerosis; sleepiness; treatment response