Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study

Neurology. 2005 Apr 12;64(7):1139-43. doi: 10.1212/01.WNL.0000158272.27070.6A.


Objective: To assess whether modafinil, a wakefulness-promoting agent, is useful for fatigue in patients with multiple sclerosis (MS).

Methods: Patients with MS with stable disability, and a baseline score of 45 or more on the Modified Fatigue Impact Scale (MFIS), were eligible for the 5-week randomized, double-blind, placebo-controlled, parallel group study. The initial daily dose of modafinil was 200 mg for 1 week. Depending on tolerance, the dose was increased by 100 mg every week up to 400 mg/day and remained unchanged between day 21 and day 35. The primary outcome variable was the change of MFIS score at day 35.

Results: A total of 115 patients with MS were enrolled in the study and in the intention to treat analysis. The mean MFIS score at baseline was 63 +/- 9 in the placebo group and 63 +/- 10 in the modafinil group. MFIS scores improved between day 0 and day 35 in both placebo-treated and modafinil-treated groups, but no significant difference was detected between the two groups. There was no major safety concern.

Conclusions: There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzhydryl Compounds / administration & dosage*
  • Benzhydryl Compounds / adverse effects
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / adverse effects
  • Double-Blind Method
  • Fatigue / drug therapy*
  • Fatigue / etiology
  • Fatigue / prevention & control
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Modafinil
  • Multiple Sclerosis / complications*
  • Placebos
  • Sleep Initiation and Maintenance Disorders / chemically induced
  • Treatment Outcome


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Placebos
  • Modafinil