The effect of modafinil on cortical excitability in patients with narcolepsy: a randomized, placebo-controlled, crossover study.
OBJECTIVE
To investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).


METHODS
Nineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.


RESULTS
Narcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P<0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.


CONCLUSIONS
Narcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.
Joo
Eun Yeon
EY
Sleep Center, Department of Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
Hong
Seung Bong
SB
Kim
He-Jung
HJ
Lim
Yang-Hee
YH
Koo
Dae-Lim
DL
Ji
Ki-Hwan
KH
Tae
Woo Suk
WS
D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil