modafinil
Last reviewed 2025-12-30
Reviewed by PsychMed Editorial Team.
Brands: Provigil
Sources updated 2025 • 4 references
General Information
Modafinil (Provigil) is a wakefulness-promoting medication indicated to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD) (label).
It is a Schedule IV controlled substance. In psychiatric practice it is sometimes used off-label for fatigue or residual sleepiness, including as augmentation in depressive disorders, but use is individualized (clinical).
Serious rash and hypersensitivity reactions are rare but safety-critical; discontinuation is recommended at the first sign of rash unless clearly not drug-related (label).
Modafinil can reduce effectiveness of steroidal contraceptives via CYP3A induction; alternative or concomitant contraception is recommended during therapy and for one month after discontinuation (label).
The modafinil compare view, evidence feed, and print page support review of activation and interaction profiles.
U.S. approvals
- Excessive sleepiness associated with narcolepsy, OSA, or shift work disorder (adults) (1998)
Formulations & strengths
- Tablets: 100 mg and 200 mg (label).
Generic availability
- Available generically.
Modafinil is widely available and can be clinically useful for excessive sleepiness, but careful patient selection is important due to psychiatric activation risk, serious rash warnings, and broad drug–drug interaction potential (label/clinical).
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
The precise mechanism is not fully established. Clinical descriptions often emphasize wake-promoting effects and effects on dopaminergic signaling (label/clinical).
In psychiatric augmentation, benefits are typically framed as improvements in fatigue and wakefulness rather than as a primary antidepressant mechanism (clinical).
- Wakefulness promotion (mechanism not fully established; label).
Metabolism and Pharmacokinetics
- Modafinil is a racemic compound with enantiomers that have different pharmacokinetics; after multiple doses the effective elimination half-life is about 15 hours (label).
- Modafinil induces CYP3A4/5 and can reduce exposure to CYP3A substrates (including steroidal contraceptives). Modafinil also inhibits CYP2C19, which can increase exposure to CYP2C19 substrates (label).
Dosing and Administration
- Narcolepsy or OSA: 200 mg once daily in the morning (label).
- Shift work disorder: 200 mg once daily ~1 hour before the work shift (label).
- Doses up to 400 mg/day have been tolerated, but the label notes no consistent evidence of added benefit beyond 200 mg/day (label).
- For OSA, modafinil is not a substitute for primary treatments; documentation of ongoing OSA management is common when used (label/clinical).
Monitoring & Labs
- Rash and hypersensitivity monitoring, especially during the first 1–5 weeks (label).
- Mood and psychiatric symptom monitoring (anxiety, agitation, mania/psychosis) (label/clinical).
- Sleep disruption monitoring (insomnia, timing effects) (clinical).
- Drug interaction review (CYP3A induction; CYP2C19 inhibition), including contraception counseling (label).
Adverse Effects
FDA boxed warnings
Common side effects (≥10%)
- Headache: Common and often dose-related (label/clinical).
- Nausea: Often improves over time; assessing food intake and hydration is common (clinical).
- Insomnia: Morning dosing and avoidance of late-day dosing can improve tolerability (clinical).
- Anxiety / agitation: Can occur; monitoring is important in anxiety and bipolar-spectrum illness (label/clinical).
- Dizziness: Can affect driving and fall risk early in treatment (clinical).
Other notable effects
- Serious rash (including Stevens-Johnson syndrome), toxic epidermal necrolysis, and DRESS have been reported; discontinuation at first rash is recommended unless clearly not drug-related (label).
- Psychiatric symptoms (psychosis, mania, suicidal ideation) have been reported; monitoring is important in vulnerable populations (label/clinical).
- Modafinil is not approved for pediatric use; pediatric trial experience included rash-related discontinuation (label).
Interactions
- CYP3A4/5 induction can reduce exposure to substrates (steroidal contraceptives, cyclosporine, midazolam, triazolam); clinical monitoring and dose adjustments may be needed (label).
- CYP2C19 inhibition can increase exposure to substrates (diazepam, propranolol, omeprazole, some tricyclic antidepressants); interaction review is important in polypharmacy (label/clinical).
- In CYP2D6 poor metabolizers, CYP2C19 can be a more important pathway for certain medications; modafinil’s CYP2C19 effects may be more clinically relevant in that context (label).
Other Useful Information
- Evidence syntheses suggest modafinil/armodafinil can improve depressive symptoms and fatigue as adjunctive therapy in some unipolar and bipolar depression trials, but benefits are variable and require monitoring for activation and insomnia (Goss 2013/clinical).
- Contraception counseling is a practical safety step because modafinil can reduce effectiveness of hormonal contraceptives through CYP3A induction (label).
References
- PROVIGIL (modafinil) tablets prescribing information — DailyMed (2025)
- Modafinil Augmentation Therapy IN Unipolar AND Bipolar Depression: A Systematic Review AND Meta Analysis OF Randomized Controlled Trials — Journal of Clinical Psychiatry (2013)
- AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)