Evaluation of the safety of modafinil for treatment of excessive sleepiness

Abstract

STUDY OBJECTIVES: Modafinil is a wake-promoting agent shown to\nimprove wakefulness in patients with excessive sleepiness\n(hypersomnolence) associated with shift work sleep disorder,\nobstructive sleep apnea, or narcolepsy. Safety and\ntolerability data from 6 randomized, double-blind,\nplacebo-controlled studies were combined to evaluate modafinil\nacross these different patient populations. METHODS: One\nthousand five hundred twenty-nine outpatients received\nmodafinil 200, 300, or 400 mg or placebo once daily for up to\n12 weeks. Assessments included recording of adverse events and\neffects of modafinil on blood pressure/heart rate,\nelectrocardiogram intervals, polysomnography, and clinical\nlaboratory parameters. RESULTS: Two hundred seventy-three\npatients with shift work sleep disorder, 292 with obstructive\nsleep apnea, and 369 with narcolepsy received modafinil; 567\nreceived placebo. Modafinil was well tolerated versus placebo,\nwith headache (34% vs 23%, respectively), nausea (11% vs\n3%), and infection (10% vs 12%) the most common adverse\nevents. Adverse events were similar across all patient groups.\nTwenty-seven serious adverse events were reported (modafinil,\nn = 18; placebo, n = 9). In modafinil-treated patients,\nclinically significant increases in diastolic or systolic\nblood pressure were infrequent (n = 9 and n = 1, respectively,\n< 1% of patients). In the studies, 1 patient in the modafinil\ngroup and 1 in the placebo group had a clinically significant\nincrease in heart rate. New clinically meaningful\nelectrocardiogram abnormalities were rare with modafinil (n =\n2) and placebo (n = 4). Clinically significant abnormalities\nin mean laboratory parameters were observed in fewer than 1%\nof modafinil-treated patients at final visit. Modafinil did\nnot affect sleep architecture in any patient population\naccording to polysomnography. CONCLUSIONS: Modafinil is well\ntolerated in the treatment of excessive sleepiness associated\nwith disorders of sleep and wakefulness and does not affect\ncardiovascular or sleep parameters.