Wakefulness-promoting agent
Exact mechanism unknown; thought to enhance hypothalamic wakefulness systems via dopamine transporter inhibition and modulation of other neurotransmitter systems including glutamate and GABA
Narcolepsy, obstructive sleep apnea (OSA)-related sleepiness, shift work sleep disorder
Augmentation in major depressive disorder (MDD), bipolar depression, fatigue in multiple sclerosis (MS), fatigue in traumatic brain injury (TBI), post-stroke executive dysfunction, post-stroke fatigue, apathy in Parkinson’s disease (PD)
Oral tablets
Start at 100 mg p.o. in the morning, titrate up to 400 mg/day as clinically indicated
100–400 mg/day
Half-life approximately 12–15 hours; metabolized primarily by the liver (CYP3A4)
Headache, nausea, nervousness, insomnia, anxiety, dry mouth
Severe rash including Stevens-Johnson syndrome (rare)
Monitor for rash and hypersensitivity reactions; assess cardiovascular status and anxiety symptoms
None
Modafinil has strong evidence for improving excessive daytime sleepiness in traumatic brain injury (TBI). It may be considered for post-stroke fatigue in select patients. Evidence for benefit in multiple sclerosis (MS) fatigue is limited but may be trialed on a case-by-case basis. Use should be individualized with careful monitoring for adverse effects and consideration of limited evidence in most neurological populations.