Efficacy and safety of
modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two
centre phase 2 study.
Rammohan KW, Rosenberg JH, Lynn DJ,
Blumenfeld AM, Pollak CP, Nagaraja HN.
Department of Neurology,
Ohio State University,
449 Means Hall, 1654 Upham Dr, Columbus, OH 43210. rammohan.2@osu.edu
J Neurol Neurosurg Psychiatry. 2002 Feb; 72(2): 179-83.
Abstract
OBJECTIVE: To assess the efficacy and
safety of modafinil for the treatment of fatigue in multiple sclerosis (MS).
METHODS: Patients aged 18-65 years with a diagnosis of MS, a stable disability
level < or =6 on the Kurtzke extended disability status scale (EDSS), and a
mean score >4 on the fatigue severity scale (FSS) were eligible for the 9
week, single blind, phase 2, two centre study. Exclusion criteria included a
diagnosis of narcolepsy, sleep apnoea, or clinically significant major
systemic disease and recent use of medications affecting fatigue. All
patients, who remained blinded for the treatment regimen, received placebo
during weeks 1-2, 200 mg/day modafinil during weeks 3-4, 400 mg/day modafinil
during weeks 5-6, and placebo during weeks 7-9. Safety was evaluated by
unblinded investigators. Efficacy was evaluated by self rating scales, using
the FSS, the modified fatigue impact scale (MFIS), a visual analogue scale for
fatigue (VAS-F), and the Epworth sleepiness scale (ESS). Adverse events were
recorded.
RESULTS: Seventy two patients (MS type: 74% relapsing-remitting; 7% primary
progressive; 19% secondary progressive) received treatment. After treatment
with 200 mg/day modafinil for 2 weeks, a significant improvement in fatigue
versus placebo run in was demonstrated. Mean scores after treatment with 200
mg/day modafinil were: FSS, 4.7 versus 5.5 for placebo (p<0.001); MFIS, 37.7
versus 44.7 (p<0.001); and VAS-F, 5.4 versus 4.5 (p=0.003). Fatigue scores for
400 mg/day modafinil were not significantly improved versus placebo run in.
Mean ESS scores were significantly improved (p<0.001) with 200 mg/day
modafinil (7.2) and 400 mg/day (7.0) versus the score at baseline (9.5).
Serious adverse events were not found at either dose. The most common adverse
events were headache, nausea, and aesthenia. Sixty five patients (90%)
completed the study.
CONCLUSIONS: These data suggest that 200 mg/day modafinil significantly
improves fatigue and is well tolerated in patients with MS.
1. Modafinil for
sustaining the alertness of helicopter pilots
2. Modafinil augmentation
of antidepressant treatment
3. Modafinil the
unique properties of a new stimulant
4. Modafinil children
with attention-deficit/hyperactivity disorder
5. Modafinil dosage
and safety
6. Modafinil successful
treatment of hypersomnia & narcolepsy
7. Modafinil narcolepsy:
symptoms and management
8. Modafinil
amplification of cortical serotonin release
9. Modafinil
treatment of alcoholic organic brain syndrome
10. Modafinil
effect on melatonin, cortisol, and growth hormone
11. Modafinil
in obstructive sleep apnea-hypopnea syndrome
12. Modafinil
vs dextroamphetamine in treatment of adult ADHD
13. Modafinil
efficacy in narcolepsy
14. Modafinil
switching from narcolepsy drugs to modafinil
15. Modafinil
dopaminergic transmission mediates CNS stimulants
