Abstract Details

Title A randomized, double-blind trial of amantadine, modafinil, and methylphenidate for the treatment of multiple sclerosis fatigue

Topic Multiple Sclerosis

Presentation(s) Emerging Science (8:00 AM-9:00 AM)

Poster/Presentation
Number 000

Objective

To compare the efficacy of amantadine, modafinil, and methylphenidate against placebo and each other in patients with MS-related fatigue.

Background

Fatigue is one of the most common and disabling symptoms of MS. Amantadine, modafinil, and methylphenidate are commonly prescribed for alleviating fatigue in MS; however, the evidence supporting their efficacy is sparse and conflicting.

Design/Methods

In this randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, patients with MS and fatigue received twice-daily oral amantadine (maximum 200mg/day), modafinil (maximum 200mg/day), methylphenidate (maximum 20mg/day) and placebo, each given for up to six weeks. The primary outcome measure was the modified fatigue impact scale (MFIS) (scores from 0 to 84, with higher numbers indicating more severe fatigue) measured while taking the maximum or highest tolerated dose. Secondary outcomes included measures of sleepiness, fatigue-related quality of life, adverse events, and the maximal tolerated dose of each medication.

Results

A total of 141 patients with a mean baseline MFIS score of 51.3 were enrolled and randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the analysis of the primary outcome. 111 participants completed all four medication periods. In the intent-to-treat analysis, the least-square means of total MFIS scores at the maximally tolerated dose were as follows: 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil and 38.7 with methylphenidate (P=0.20 for the overall medication effect; P>0.05 for all pairwise comparisons). There was no statistically significant difference in the physical and cognitive subscales of MFIS and NeuroQoL fatigue item bank T-score between placebo and the other study medications. Analyses of safety and tolerability data are pending.

Conclusions

Amantadine, modafinil, and methylphenidate were not superior to placebo in improving MS-related fatigue. The results of this study do not support the use of these medications for the treatment of fatigue in MS.

Authors/Disclosures
Bardia Nourbakhsh, MD (Johns Hopkins University) PRESENTER	The institution of Dr. Nourbakhsh has received research support from Genentech. The institution of Dr. Nourbakhsh has received research support from national MS Society . The institution of Dr. Nourbakhsh has received research support from Department of Defense. The institution of Dr. Nourbakhsh has received research support from NIH.
	No disclosure on file
	No disclosure on file
Christian Cordano, MD, PhD (UCSF)	Dr. Cordano has nothing to disclose.
	No disclosure on file
	No disclosure on file
Kristen M. Krysko, MD (St. Michael's Hospital)	Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Krysko has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. Krysko has received research support from MS Society of Canda. The institution of Dr. Krysko has received research support from Roche.
Alice Edwards, DO (Neurology Specialists)	The institution of Dr. Rutatangwa has received research support from NIH.
Salman Aljarallah, MD	Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Sanofi Genzyme.
	No disclosure on file
Ellen M. Mowry, MD, FAAN (Johns Hopkins University)	Dr. Mowry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BeCareLink, LLC. The institution of Dr. Mowry has received research support from Biogen. The institution of Dr. Mowry has received research support from Genentech. Dr. Mowry has received publishing royalties from a publication relating to health care.
	No disclosure on file
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.

��ɫ��

��ɫ��