Modafinil In Multiple Sclerosis Fatigue

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.

Background
Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants.

Results of a placebo-controlled study showed it to improve Fatigue in Multiple Sclerosis (MS) at a dose of 200 mg daily, but not at a dose of 400 mg daily.

Objective
To establish the efficacy, safety and appropriate dose of Modafinil in the treatment of Fatigue and sleepiness in patients with Multiple Sclerosis.

Method
A total of 50 patients diagnosed with MS (mean age 40.4 +/- 10.3 years, 30 females/20 males.

MS type: 36 Relapsing/Remitting, 1 Primary/Progressive, 13 Secondary/Progressive; mean disability level 3.8 +/- 1.5 on the Kurtzke EDSS) and complaining of chronic Fatigue were enrolled in a prospective 3-month, two-center, open-label study.

Efficacy was evaluated with the Fatigue Severity Scale (FSS, score range 0-42), the Epworth Sleepiness Scale (ESS, score range 0-24).

And by subjective patient appraisal of change of Fatigue, quality of life and overall satisfaction with treatment. Adverse Effects (AEs) were recorded throughout the study.

Treatment was started with a single daily dose of 100 mg in all patients. In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg.

Results
Three patients discontinued Modafinil because of AEs (Nervousness, Dizziness). Two patients (4 %) were treated with 50 mg, 25 (50 %) with 100 mg, 21 (42 %) with 200 mg and 2 (4 %) with 300 mg daily.

No patient required 400 mg daily. Mean FSS scores were 30.3 +/- 8.5 at baseline and 25.4 +/- 3.7 at 3 months (p < 0.0001).

Mean ESS scores were 9.7 +/- 3.9 at baseline and 4.9 +/- 2.9 at 3 months (p < 0.0001).

Self-appraisal of change of Fatigue showed clear improvement in 41 patients (87.2 %), some improvement in 4 (8.5 %) and no change in 2 (4.3 %).

Overall clinical condition was clearly improved in 43 patients (91.5 %), somewhat improved in 1 patient (2.1 %), and unchanged in 3 patients (6.4 %).

No patient reported worsening of overall clinical condition.

Conclusions
Treatment with Modafinil significantly improves Fatigue and sleepiness and is well tolerated by patients with MS.

Unlike the higher dose regimen required in Narcolepsy, a low-dose regimen of Modafinil is effective in MS.