Evaluation of the safety of modafinil for treatment of excessive sleepiness.
OBJECTIVE
Modafinil is a wake-promoting agent shown to improve wakefulness in patients with excessive sleepiness (hypersomnolence) associated with shift work sleep disorder, obstructive sleep apnea, or narcolepsy. Safety and tolerability data from 6 randomized, double-blind, placebo-controlled studies were combined to evaluate modafinil across these different patient populations.


METHODS
One thousand five hundred twenty-nine outpatients received modafinil 200, 300, or 400 mg or placebo once daily for up to 12 weeks. Assessments included recording of adverse events and effects of modafinil on blood pressure/heart rate, electrocardiogram intervals, polysomnography, and clinical laboratory parameters.


RESULTS
Two hundred seventy-three patients with shift work sleep disorder, 292 with obstructive sleep apnea, and 369 with narcolepsy received modafinil; 567 received placebo. Modafinil was well tolerated versus placebo, with headache (34% vs 23%, respectively), nausea (11% vs 3%), and infection (10% vs 12%) the most common adverse events. Adverse events were similar across all patient groups. Twenty-seven serious adverse events were reported (modafinil, n = 18; placebo, n = 9). In modafinil-treated patients, clinically significant increases in diastolic or systolic blood pressure were infrequent (n = 9 and n = 1, respectively, < 1% of patients). In the studies, 1 patient in the modafinil group and 1 in the placebo group had a clinically significant increase in heart rate. New clinically meaningful electrocardiogram abnormalities were rare with modafinil (n = 2) and placebo (n = 4). Clinically significant abnormalities in mean laboratory parameters were observed in fewer than 1% of modafinil-treated patients at final visit. Modafinil did not affect sleep architecture in any patient population according to polysomnography.


CONCLUSIONS
Modafinil is well tolerated in the treatment of excessive sleepiness associated with disorders of sleep and wakefulness and does not affect cardiovascular or sleep parameters.
Roth
Thomas
T
Henry Ford Sleep Disorders Center, Detroit, MI 48202, USA. TRoth1@hfhs.org
Schwartz
Jonathan R L
JR
Hirshkowitz
Max
M
Erman
Milton K
MK
Dayno
Jeffrey M
JM
Arora
Sanjay
S
D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D045422:Continuous Positive Airway Pressure; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009325:Nausea / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil