Modafinil
Provigil
Wakefulness-Promoting AgentSchedule IVGeneric availableTDM data
The precise mechanism of modafinil is unknown. It binds to the dopamine transporter (DAT) and inhibits dopamine reuptake, but differs from amphetamines in that it does not appear to directly release monoamines. It also appears to increase histamine release from the tuberomammillary nucleus and may activate orexin/hypocretin neurons. Unlike amphetamines, modafinil does not cause peripheral sympathomimetic effects at therapeutic doses.
Compare Modafinil →FDA-Approved Indications
- Improve wakefulness in adults with excessive sleepiness associated with narcolepsy
- Improve wakefulness in adults with excessive sleepiness associated with obstructive sleep apnea (adjunct to standard treatment)
- Improve wakefulness in adults with excessive sleepiness associated with shift work disorder
What Sets This Drug Apart
- Schedule IV controlled substance — lower abuse potential than Schedule II stimulants despite DAT-mediated mechanism
- Wakefulness-promoting without peripheral sympathomimetic effects — does not increase catecholamine release like amphetamines
- Moderate CYP3A4 inducer — reduces oral contraceptive efficacy (backup contraception required)
- Headache in 34% — the most common side effect and significantly higher than placebo
- Serious dermatologic reactions (SJS/TEN) reported — FDA rejected pediatric indication due to a case of SJS in clinical trials
- No evidence that doses >200 mg/day provide additional benefit — flat dose-response curve