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 fatigue, post-stroke apathy, 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. There is no established benefit for fatigue in Parkinson’s disease or dementia. Use should be individualized with careful monitoring for adverse effects and consideration of limited evidence in most neurological populations.