Evaluation of the safety of modafinil for treatment of excessive sleepiness

Abstract

STUDY OBJECTIVES: Modafinil is a wake-promoting agent shown to\textbackslashnimprove wakefulness in patients with excessive sleepiness\textbackslashn(hypersomnolence) associated with shift work sleep disorder,\textbackslashnobstructive sleep apnea, or narcolepsy. Safety and\textbackslashntolerability data from 6 randomized, double-blind,\textbackslashnplacebo-controlled studies were combined to evaluate modafinil\textbackslashnacross these different patient populations. METHODS: One\textbackslashnthousand five hundred twenty-nine outpatients received\textbackslashnmodafinil 200, 300, or 400 mg or placebo once daily for up to\textbackslashn12 weeks. Assessments included recording of adverse events and\textbackslashneffects of modafinil on blood pressure/heart rate,\textbackslashnelectrocardiogram intervals, polysomnography, and clinical\textbackslashnlaboratory parameters. RESULTS: Two hundred seventy-three\textbackslashnpatients with shift work sleep disorder, 292 with obstructive\textbackslashnsleep apnea, and 369 with narcolepsy received modafinil; 567\textbackslashnreceived placebo. Modafinil was well tolerated versus placebo,\textbackslashnwith headache (34% vs 23%, respectively), nausea (11% vs\textbackslashn3%), and infection (10% vs 12%) the most common adverse\textbackslashnevents. Adverse events were similar across all patient groups.\textbackslashnTwenty-seven serious adverse events were reported (modafinil,\textbackslashnn = 18; placebo, n = 9). In modafinil-treated patients,\textbackslashnclinically significant increases in diastolic or systolic\textbackslashnblood pressure were infrequent (n = 9 and n = 1, respectively,\textbackslashn\textless 1% of patients). In the studies, 1 patient in the modafinil\textbackslashngroup and 1 in the placebo group had a clinically significant\textbackslashnincrease in heart rate. New clinically meaningful\textbackslashnelectrocardiogram abnormalities were rare with modafinil (n =\textbackslashn2) and placebo (n = 4). Clinically significant abnormalities\textbackslashnin mean laboratory parameters were observed in fewer than 1%\textbackslashnof modafinil-treated patients at final visit. Modafinil did\textbackslashnnot affect sleep architecture in any patient population\textbackslashnaccording to polysomnography. CONCLUSIONS: Modafinil is well\textbackslashntolerated in the treatment of excessive sleepiness associated\textbackslashnwith disorders of sleep and wakefulness and does not affect\textbackslashncardiovascular or sleep parameters.