Modafinil
Wakefulness-promoting agent, FDA-approved for narcolepsy, shift work sleep disorder, OSA adjunct. DEA Schedule IV. Off-label cognitive enhancement framing separate in MolekulaX Nootropic library.
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Related comparisons
Modafinil vs MethylphenidateDETAILED OVERVIEW
What is Modafinil?
Modafinil is a wakefulness-promoting agent developed by Cephalon (now Teva) (Provigil, FDA 1998). ATC code N06BA07 (CNS stimulants). Official FDA indications: narcolepsy, shift work sleep disorder (SWSD), obstructive sleep apnea (OSA) residual sleepiness adjunct. Clinically documented off-label use (cognitive enhancement, fatigue reduction, MS-associated fatigue, second-line ADHD) is detailed in the MolekulaX Nootropic library. This pharma entry focuses on official Rx indications. Mechanism: dopamine reuptake inhibitor (DAT), activation of histamine and orexin systems in the hypothalamus, selectively promoting wakefulness without the global CNS activation of classic stimulants (amphetamine, methylphenidate).
ATC code
N06BA07
Prescription
Prescription only (Rx), DEA Schedule IV (USA)
Mechanism
DAT inhibitor + histamine/orexin activation
Half-life
12-15 h
Onset
30-60 min, peak 2-4 h
Anecdotal reports describe Modafinil as one of the most functional cognitive enhancers, with users noting baseline energy that feels extended for hours without a pronounced peak or crash. Because it modulates orexin and histamine, appetite suppression and significant reductions in sleep drive are common, which is why early-morning dosing upon waking is consistently recommended given the 12-15 hour half-life. Modest cortisol elevations contribute to a task-focused, in-the-moment state. Community accounts note tolerance builds slower than with traditional stimulants, though psychological reliance on the productivity boost can develop. CYP-mediated hepatic metabolism creates potential drug-interaction considerations. Compared to Fladrafinil, Modafinil feels smoother, shorter-lasting, and less wired. Lower doses can be effective in sensitive individuals.
⚠ Not clinical evidence – based on user accounts.
Data console
Lab data
Yan Z, Li J, Yu Y . Comparative efficacy of new wake-promoting agents for narcolepsy-a network meta-analysis.. BMC Neurol.
Black JE, Hull SG, Tiller J, Yang R, Harsh JR . The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy.. J Clin Sleep Med.
Rammohan KW, Rosenberg JH, Lynn DJ et al. . Modafinil in the treatment of multiple sclerosis-related fatigue. J Neurol Neurosurg Psychiatry. 2002;72(2):179-83..
Czeisler CA, Walsh JK, Wesnes KA et al. . Sustained efficacy of armodafinil in shift work disorder. Mayo Clin Proc. 2009;84(11):958-72..
Battleday RM, Brem AK. . Cognitive effects of modafinil in normal healthy people: a systematic review. Eur Neuropsychopharmacol. 2015;25(11):1865-81..
Black J, Houghton WC. . Sodium oxybate plus modafinil in narcolepsy with cataplexy. Sleep. 2006;29(7):939-46..
Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C . Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy.. Sleep Med.
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Serious skin and hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, multi-organ hypersensitivity), typically in the first 1–4 weeks, FDA serious warning, stop immediately at any rash.
- Psychiatric effects: anxiety, irritability, insomnia, and less commonly mania, psychosis, hallucinations, aggression and suicidal ideation, especially with a psychiatric history.
- Cardiovascular effects: mild increases in blood pressure and heart rate, palpitations, rarely chest pain and arrhythmia; blood pressure monitoring advised.
- Headache (the most common, around 35%), usually easing after the first week.
- Nausea, dry mouth, decreased appetite and weight loss.
- Insomnia if dosed too late in the day (around ≥2 pm), so once-daily morning dosing is recommended.
- Psychological dependence and abuse potential (DEA Schedule IV, low but not zero), especially when tied to performance expectations; physical tolerance is rare.
Contraindications · 4
- Prior severe skin reaction (Stevens-Johnson syndrome, TEN, DRESS) history
- Severe CV disease: LV hypertrophy, mitral valve prolapse with IHSS
- Known modafinil hypersensitivity
- Psychosis, severe anxiety disorder (relative)
Related Pharmaceuticals
Same therapeutic category
Studies
Related research and clinical findings
Comparative efficacy of new wake-promoting agents for narcolepsy-a network meta-analysis.
Yan Z, Li J, Yu Y
The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy.
Black JE, Hull SG, Tiller J, Yang R, Harsh JR
Modafinil in the treatment of multiple sclerosis-related fatigue
Rammohan KW, Rosenberg JH, Lynn DJ et al.
Sustained efficacy of armodafinil in shift work disorder
Czeisler CA, Walsh JK, Wesnes KA et al.
Cognitive effects of modafinil in normal healthy people: a systematic review
Battleday RM, Brem AK.
Sodium oxybate plus modafinil in narcolepsy with cataplexy
Black J, Houghton WC.
Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy.
Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C
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The information here is for educational and scientific purposes only. Medication use requires medical consultation and a prescription. The indications, dose ranges, and side effects listed here do NOT replace the official Summary of Product Characteristics (SmPC) or consultation with a physician. Do not start or stop any medication on your own. In an emergency, call your local emergency number.