Effect of modafinil on cerebral blood flow in narcolepsy patients

Background: To investigate the effects of modafinil on regional cerebral blood flow (rCBF) in narcolepsy, we performed ^99mTc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo medication. Methods: Brain SPECT was performed twice during the awake state before and after modafinil or placebo administration for 4 weeks in 43 drug-naïve narcoleptics with cataplexy (M/F = 23/20, 29.5 ± 5.8 years). For SPM analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- and post-modafinil or placebo SPECT images. Results: The mean modafinil dose used was 207.8 ± 62.3 mg/day. Modafinil significantly reduced Epworth Sleepiness Scale scores from 20.3 ± 2.1 to 5.2 ± 3.1 (P < 0.01), while placebo did not. Compared to the off-modafinil condition, the on-modafinil condition showed significantly increased rCBF in the right dorsolateral and bilateral medial prefrontal cortices. Conversely, after modafinil administration, rCBF was decreased in bilateral precentral gyri, left hippocampus, left fusiform gyrus, bilateral lingual gyri, and cerebellum. There was no significant rCBF change after placebo administration. Conclusion: By a chronic administration of modafinil in narcoleptic patients, rCBF increased in the bilateral prefrontal cortices, whereas it decreased in left mesio/basal, temporal, bilateral occipital areas, and cerebellum.