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 400 mg 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 3 h 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.