Excessive sleepiness in disorders of sleep and wakefulness can be caused by sleep-wake dysregulation (eg, narcolepsy), circadian misalignment (eg, shift work sleep disorder [SWSD]), or sleep disruption (eg, obstructive sleep apnea/hypopnea syndrome [OSAHS]). Modafinil, a novel wake-promoting agent with low abuse potential, is indicated to improve wakefulness in patients with excessive sleepiness in narcolepsy, SWSD, and OSAHS (when used as adjunctive treatment of residual sleepiness in regular nCPAP users). The tolerability of modafinil was evaluated from placebo-controlled studies in these disorders.
Tolerability data were combined from 6 placebo-controlled studies: 2 studies each in narcolepsy, chronic SWSD, and residual excessive sleepiness in OSAHS. Assessments included adverse events and effects of modafinil on blood pressure/heart rate, electrocardiogram intervals, and clinical laboratory parameters.
369 patients with narcolepsy, 273 with SWSD, and 292 with OSAHS received modafinil; 567 received placebo. The most common adverse events that occurred in ≥ 5% of patients and were greater for modafinil than placebo were headache (34% vs 23%), nausea (11% vs 3%), rhinitis (7% vs 6%), nervousness (7% vs 3%), back pain (6% vs 5%), and diarrhea (6% vs 5%). Most adverse events were transient, mild to moderate in nature, and occurred within the first month of treatment. The adverse event profile for modafinil was similar among the disorders studied, except for headache, which was more frequent in narcolepsy. Overall, 8% of modafinil and 3% of placebo patients discontinued treatment due to adverse events. Modafinil had no clinically significant adverse effects on blood pressure/heart rate, electrocardiogram intervals, or clinical laboratory evaluations compared with placebo.
Modafinil is well tolerated in patients with excessive sleepiness associated with specific disorders of sleep and wakefulness with a low incidence of adverse events, most of which were transient and mild-to-moderate in severity.
Modafinil is a well-tolerated therapy that can be used in effectively improving wakefulness in patients with specific sleep-wake disorders without evidence of effects on blood pressure, heart rate, ECG intervals, or laboratory measures.
M.J. Thorpy, Cephalon, Inc.