Modafinil
updated
What is Modafinil?
Modafinil is a 1:1 racemic mixture of R- and S-enantiomers. Armodafinil is the R-enantiomer sold as a separate drug. The R component clears more slowly, so the products have different exposure curves and their milligram strengths and trial results should not be swapped.
Modafinil improves wakefulness short term in adults with narcolepsy, treated obstructive sleep apnea, and diagnosed shift-work disorder. Benefits are incomplete, the drug does not treat an obstructed airway, and small single-dose studies in rested healthy adults do not establish broad everyday cognitive enhancement.
Racemic Schedule IV wake-promoting agent
- US approval covers excessive sleepiness associated with narcolepsy, OSA, and SWD in adults.
- In OSA it is an adjunct for residual sleepiness while the underlying obstruction remains treated.
- The 209-person SWD trial found modest gains but persistent sleepiness and impaired performance.
- Two rested healthy trials produced mixed, task-specific results rather than a general cognition effect.
- The label carries serious rash, psychiatric, driving, cardiovascular, contraceptive, and metabolic-interaction warnings.
- Modafinil is a racemate; armodafinil is the R-enantiomer and a separate prescription product.
Is this treatment of a sleep disorder or an enhancement claim?
US Provigil is approved to improve wakefulness in adults with excessive sleepiness tied to narcolepsy, obstructive sleep apnea, or shift-work disorder. The approval does not cover cognitive enhancement in rested healthy people.
| Question | Best direct evidence |
|---|---|
| Narcolepsy sleepiness | Two labeled nine-week programs; one 271-person primary trial is detailed below |
| Residual sleepiness in treated OSA | Adjunctive trials while effective CPAP continued |
| Sleepiness during diagnosed chronic SWD | A 209-person three-month night-shift trial |
| Cognition in rested healthy adults | Small single-dose laboratory trials with mixed, task-specific results |
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original source271 adults · wakefulness improved, sleepiness returned
Randomized double-blind placebo-controlled trial
US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000. PMID 10720292.
In a 21-center trial, 271 modafinil-naive adults with narcolepsy received fixed oral modafinil 200 mg, 400 mg, or placebo for nine weeks; 240 entered a two-week discontinuation phase. Both objective sleep-latency measures, self-rated Epworth sleepiness, and clinician global change improved. Excessive daytime sleepiness returned to baseline after withdrawal, while amphetamine-like withdrawal symptoms were not reported in the two-week observation.
- Participants / model
- 271 adults with narcolepsy and objectively documented excessive daytime sleepiness
- Treatment
- Oral modafinil 200 mg, 400 mg, or placebo
- Follow-up
- 9 treatment weeks plus 2-week discontinuation phase
- Study design
- Randomized double-blind placebo-controlled 21-center trial
- Funding
- Cephalon program
The abstract does not provide every arm's absolute change. Return of sleepiness is not the same as a withdrawal syndrome, and two weeks cannot exclude every discontinuation effect.
Read the original source157 adults · ESS improved, objective normalization did not
Randomized double-blind placebo-controlled trial
Pack AI et al. American Journal of Respiratory and Critical Care Medicine. 2001. PMID 11719309.
In 157 adults with OSA and residual sleepiness despite regular effective CPAP, four weeks of modafinil improved Epworth Sleepiness Scale and mean sleep latency versus placebo. ESS normalized in 51 percent versus 27 percent. The proportion with a normal Multiple Sleep Latency Test did not differ, 29 percent versus 25 percent. Mean CPAP use stayed about 6.2 hours nightly in both groups.
- Participants / model
- 157 adults with OSA, residual sleepiness, and regular effective CPAP use
- Treatment
- Oral modafinil, 200 mg in week 1 then 400 mg in weeks 2 to 4, or placebo; CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon-associated pivotal program
The trial treated residual sleepiness after effective CPAP, not obstruction. It was short, and objective sleep-latency normalization was not significantly different.
Read the original source209 workers · modest benefit with residual impairment
Randomized double-blind placebo-controlled trial
Czeisler CA et al. New England Journal of Medicine. 2005. PMID 16079371.
In 209 adults with chronic shift-work sleep disorder, modafinil 200 mg before each night shift for three months increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo. CGI improvement was 74 versus 36 percent, attention lapses fell, and 29 versus 54 percent reported an accident or near accident on the commute home. Treated participants still had excessive sleepiness and impaired nighttime performance.
- Participants / model
- 209 adults with at least three months of diagnosed SWD, at least five night shifts monthly, objective sleepiness, and daytime insomnia
- Treatment
- Oral modafinil 200 mg or placebo before each night shift
- Follow-up
- 3 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon and National Institute for Occupational Safety and Health support; sponsor representatives helped design and analyze the study
The accident or near-accident outcome was self-reported. Multiple outcomes were tested, and the improvement did not normalize sleepiness or performance.
Read the original source64 rested adults · gains on some difficult tasks
Randomized double-blind placebo-controlled trial
Muller U et al. Neuropharmacology. 2013. PMID 22820554; PMCID PMC3485563.
Sixty-four non-sleep-deprived healthy adults received one oral 200 mg dose of modafinil or placebo. The modafinil group did better on the hardest levels of spatial working memory, planning, and decision tasks and on delayed visual pattern recognition, and reported greater task enjoyment. It did not improve paired-associate learning; overall mood did not change; creativity findings were inconsistent and nonsignificant.
- Participants / model
- 64 healthy non-sleep-deprived volunteers, 32 per group
- Treatment
- Single oral modafinil 200 mg or placebo
- Follow-up
- Single laboratory session
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
- Funding
- Wellcome Trust and Medical Research Council support; two authors reported industry relationships
This small, single-dose, multi-endpoint laboratory study did not measure sustained school or workplace output, daily function, or repeated-use safety.
Read the original source60 rested students · mostly null, limited task effects
Randomized double-blind placebo-controlled trial
Randall DC et al. Journal of Psychopharmacology. 2005. PMID 15738750.
Sixty healthy student volunteers aged 19 to 22 received a single 100 mg dose, 200 mg dose, or placebo. Several attention, spatial working-memory, long-term-memory, executive, visuospatial, and fluency tests were null. Some immediate verbal recall, visual recognition, sustained-attention, and color-naming outcomes differed, without a consistent dose pattern; 200 mg slowed pattern-recognition responses.
- Participants / model
- 60 healthy non-sleep-deprived students aged 19 to 22
- Treatment
- Single oral modafinil 100 mg, 200 mg, or placebo
- Follow-up
- Single laboratory session, testing two hours after dosing
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
Small arms and many cognitive endpoints increase the risk of unstable positive findings. A single laboratory session does not establish durable real-world enhancement.
Read the original sourceWhat did the narcolepsy trial improve, and what happened after stopping?
In 271 adults with narcolepsy, nine weeks of modafinil improved objective ability to stay awake, objective tendency to fall asleep, Epworth sleepiness, and clinician global ratings versus placebo. It treated excessive daytime sleepiness; it was not presented as a cure for narcolepsy.
Of 271 randomized participants, 240 entered a two-week discontinuation phase. Sleepiness returned to baseline in prior modafinil recipients, but the study did not report an amphetamine-like withdrawal syndrome during that short window. Benefit depended on continued treatment, while classic withdrawal signs were not seen in this trial.
271 adults · wakefulness improved, sleepiness returned
Randomized double-blind placebo-controlled trial
US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000. PMID 10720292.
In a 21-center trial, 271 modafinil-naive adults with narcolepsy received fixed oral modafinil 200 mg, 400 mg, or placebo for nine weeks; 240 entered a two-week discontinuation phase. Both objective sleep-latency measures, self-rated Epworth sleepiness, and clinician global change improved. Excessive daytime sleepiness returned to baseline after withdrawal, while amphetamine-like withdrawal symptoms were not reported in the two-week observation.
- Participants / model
- 271 adults with narcolepsy and objectively documented excessive daytime sleepiness
- Treatment
- Oral modafinil 200 mg, 400 mg, or placebo
- Follow-up
- 9 treatment weeks plus 2-week discontinuation phase
- Study design
- Randomized double-blind placebo-controlled 21-center trial
- Funding
- Cephalon program
The abstract does not provide every arm's absolute change. Return of sleepiness is not the same as a withdrawal syndrome, and two weeks cannot exclude every discontinuation effect.
Read the original sourceUS label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceWhat improves in OSA, and what does modafinil leave untreated?
It can improve residual sleepiness in selected adults whose airway obstruction is already being treated. It does not open the airway, reduce the underlying obstruction, or replace CPAP when CPAP is the chosen treatment.
| Trial | Sleepiness result | Study condition |
|---|---|---|
| US, 157 adults, 4 weeks | ESS normalization 51% vs 27%; MSLT normalization 29% vs 25% | Objective normalization was not significantly different; CPAP continued |
| Japan, 114 adults, 4 weeks | ESS -6.6 vs -2.4; MWT subset +2.8 vs -0.4 min | AHI and nocturnal sleep measures changed similarly; effective adherent CPAP continued |
The Japanese trial required at least three months of nasal CPAP, use on at least 70 percent of nights for at least four hours, and an AHI of 10 or less. That selection is why the result cannot be carried into untreated or poorly treated obstruction.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original source157 adults · ESS improved, objective normalization did not
Randomized double-blind placebo-controlled trial
Pack AI et al. American Journal of Respiratory and Critical Care Medicine. 2001. PMID 11719309.
In 157 adults with OSA and residual sleepiness despite regular effective CPAP, four weeks of modafinil improved Epworth Sleepiness Scale and mean sleep latency versus placebo. ESS normalized in 51 percent versus 27 percent. The proportion with a normal Multiple Sleep Latency Test did not differ, 29 percent versus 25 percent. Mean CPAP use stayed about 6.2 hours nightly in both groups.
- Participants / model
- 157 adults with OSA, residual sleepiness, and regular effective CPAP use
- Treatment
- Oral modafinil, 200 mg in week 1 then 400 mg in weeks 2 to 4, or placebo; CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon-associated pivotal program
The trial treated residual sleepiness after effective CPAP, not obstruction. It was short, and objective sleep-latency normalization was not significantly different.
Read the original source114 Japanese adults · residual sleepiness on optimal CPAP
Randomized double-blind placebo-controlled trial
Inoue Y, Takasaki Y, Yamashiro Y. Journal of Clinical Sleep Medicine. 2013. PMID 23946704.
At 37 Japanese sleep sites, 114 adults with residual sleepiness despite at least three months of adherent, effective nasal CPAP were randomized to oral modafinil 200 mg or placebo for four weeks. ESS changed by -6.6 versus -2.4, and the 50-person MWT subset changed by +2.8 versus -0.4 minutes. AHI and nocturnal polysomnography changed similarly between groups. Adverse drug reactions occurred in 36.5 versus 22.6 percent, a nonsignificant difference.
- Participants / model
- 114 Japanese adults with ESS at least 11, AHI at most 10 on CPAP, and documented CPAP adherence
- Treatment
- Oral modafinil 200 mg daily or placebo while nasal CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled 37-site trial
- Funding
- Alfresa Pharma supplied study medication and had employees among the authors
Only 50 participants underwent MWT. Four weeks and selected adherent CPAP users do not answer long-term outcomes or untreated OSA.
Read the original sourceWhat does the Chinese OSA dossier add, and what is missing?
It adds a domestic population and formulation bridge, but the public evidence is a sponsor filing rather than a full trial report. The filing says a 209-person randomized placebo-controlled OSA sleepiness trial supported Chinese review and reports composite response of 80.2 versus 45.0 percent and a translated 'recovery' rate of 14.85 versus 3.00 percent.
The same Chinese-language file says pharmacokinetic testing found 200 mg dispersible tablets, conventional tablets, and capsules bioequivalent, and says the domestic efficacy program studied OSA only. That is why the local capsule indication was limited to wake promotion in adults sleepy from OSA.
China dossier · 209-person OSA trial and formulation bridge
Public reimbursement submission citing regulatory review
Hunan Welman Pharmaceutical Co. Public submission for the 2022 National Reimbursement Drug List adjustment, filed July 14, 2022.
The Chinese-language public dossier says a 209-person randomized placebo-controlled domestic OSA sleepiness trial supported local review. It reports an 80.2 percent versus 45.0 percent composite response and 14.85 percent versus 3.00 percent 'recovery' rate. It also says 200 mg dispersible tablets, tablets, and capsules were bioequivalent and that only OSA was studied domestically, so the Chinese capsule indication was limited to wake promotion in adults sleepy from OSA.
- Participants / model
- 209 participants in a Chinese domestic OSA excessive-sleepiness trial; healthy Chinese volunteers in formulation pharmacokinetic studies
- Treatment
- Oral modafinil dispersible tablet versus placebo; separate bioequivalence comparisons among dispersible tablets, tablets, and capsules
- Follow-up
- Trial duration and arm allocation not stated in the public dossier excerpt
- Study design
- Sponsor reimbursement submission summarizing a randomized placebo-controlled trial and Chinese regulatory technical review
- Funding
- Submitted by Hunan Welman Pharmaceutical Co.; sponsor-authored public filing
The public dossier does not report arm sizes, duration, response definition, confidence intervals, attrition, or complete safety results. 痊愈 is translated as 'recovery,' but no operational definition is supplied.
Read the original sourceDid the shift-work trial normalize alertness?
In 209 adults with diagnosed chronic SWD, three months of modafinil increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo, and 74 versus 36 percent were rated at least minimally improved. Sleepiness and impaired performance persisted.
Attention lapses fell. Twenty-nine percent of treated participants versus 54 percent on placebo reported an accident or near accident on the commute home, a self-reported secondary outcome. Treated participants still had excessive sleepiness and impaired performance at night, so residual driving risk remained.
209 workers · modest benefit with residual impairment
Randomized double-blind placebo-controlled trial
Czeisler CA et al. New England Journal of Medicine. 2005. PMID 16079371.
In 209 adults with chronic shift-work sleep disorder, modafinil 200 mg before each night shift for three months increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo. CGI improvement was 74 versus 36 percent, attention lapses fell, and 29 versus 54 percent reported an accident or near accident on the commute home. Treated participants still had excessive sleepiness and impaired nighttime performance.
- Participants / model
- 209 adults with at least three months of diagnosed SWD, at least five night shifts monthly, objective sleepiness, and daytime insomnia
- Treatment
- Oral modafinil 200 mg or placebo before each night shift
- Follow-up
- 3 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon and National Institute for Occupational Safety and Health support; sponsor representatives helped design and analyze the study
The accident or near-accident outcome was self-reported. Multiple outcomes were tested, and the improvement did not normalize sleepiness or performance.
Read the original sourceUS label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceWhat did modafinil do after 44 hours awake?
A small laboratory experiment found some task-specific effects under extreme sleep deprivation. It did not simulate ordinary studying, office work, or a slightly short night of sleep.
Fifty-four healthy adults were kept awake for 44 hours, then randomized to modafinil 400 mg (n=12), caffeine 600 mg (n=12), dextroamphetamine 20 mg (n=16), or placebo (n=14). All active drugs supported vigilance and alertness. The modafinil and dextroamphetamine groups used fewer moves on a planning task, while modafinil participants also deliberated longer. The relevant executive tasks had no rested baseline.
54 healthy adults · severe deprivation, tiny arms
Randomized double-blind active- and placebo-controlled experiment
Killgore WDS et al. Aviation, Space, and Environmental Medicine. 2008. PMID 19238808; PMCID PMC2635585.
Fifty-four healthy adults stayed awake for 44 hours before receiving modafinil 400 mg (n=12), caffeine 600 mg (n=12), dextroamphetamine 20 mg (n=16), or placebo (n=14). All three active drugs supported vigilance and alertness. Modafinil and dextroamphetamine groups used fewer moves on the Tower of London task, while the modafinil group also deliberated longer. The relevant executive tasks had no rested baseline.
- Participants / model
- 54 healthy adults under 44 hours of total sleep deprivation
- Treatment
- Single oral modafinil 400 mg, caffeine 600 mg, dextroamphetamine 20 mg, or placebo
- Follow-up
- Single exposure with testing during roughly hours 45 to 50 awake
- Study design
- Randomized double-blind active- and placebo-controlled laboratory experiment
- Funding
- US Army Medical Research and Materiel Command
The modafinil arm had 12 people, the doses were high single exposures, and the design cannot answer routine rested use or long-term safety.
Read the original sourceWhat do direct trials in rested healthy adults show?
A mixed, task-level pattern. One 64-person trial found improvements on the hardest levels of several tests. Another 60-person trial found many null domains, scattered positive results, no consistent dose pattern, and slower responses on one memory task at 200 mg. Neither establishes broad or durable real-world enhancement.
| Study | Positive findings | Null or adverse findings |
|---|---|---|
| 64 adults, 200 mg vs placebo | Hardest spatial working-memory, planning, decision tasks; delayed pattern recognition; task enjoyment | Paired-associate learning null; overall mood null; creativity inconsistent and nonsignificant |
| 60 students, 100 mg, 200 mg, or placebo | Some verbal span, pattern recognition, sustained attention, and color naming | Many attention, executive, long-term-memory, visuospatial, and fluency outcomes null; no clean dose-response; slower pattern recognition at 200 mg |
Multiple tests create many chances for a positive result, and both studies used one dose in a laboratory. They did not measure grades, completed work, costly mistakes, repeated-use benefit, or long-term safety.
64 rested adults · gains on some difficult tasks
Randomized double-blind placebo-controlled trial
Muller U et al. Neuropharmacology. 2013. PMID 22820554; PMCID PMC3485563.
Sixty-four non-sleep-deprived healthy adults received one oral 200 mg dose of modafinil or placebo. The modafinil group did better on the hardest levels of spatial working memory, planning, and decision tasks and on delayed visual pattern recognition, and reported greater task enjoyment. It did not improve paired-associate learning; overall mood did not change; creativity findings were inconsistent and nonsignificant.
- Participants / model
- 64 healthy non-sleep-deprived volunteers, 32 per group
- Treatment
- Single oral modafinil 200 mg or placebo
- Follow-up
- Single laboratory session
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
- Funding
- Wellcome Trust and Medical Research Council support; two authors reported industry relationships
This small, single-dose, multi-endpoint laboratory study did not measure sustained school or workplace output, daily function, or repeated-use safety.
Read the original source60 rested students · mostly null, limited task effects
Randomized double-blind placebo-controlled trial
Randall DC et al. Journal of Psychopharmacology. 2005. PMID 15738750.
Sixty healthy student volunteers aged 19 to 22 received a single 100 mg dose, 200 mg dose, or placebo. Several attention, spatial working-memory, long-term-memory, executive, visuospatial, and fluency tests were null. Some immediate verbal recall, visual recognition, sustained-attention, and color-naming outcomes differed, without a consistent dose pattern; 200 mg slowed pattern-recognition responses.
- Participants / model
- 60 healthy non-sleep-deprived students aged 19 to 22
- Treatment
- Single oral modafinil 100 mg, 200 mg, or placebo
- Follow-up
- Single laboratory session, testing two hours after dosing
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
Small arms and many cognitive endpoints increase the risk of unstable positive findings. A single laboratory session does not establish durable real-world enhancement.
Read the original sourceIs modafinil's mechanism actually known?
Only partly. The label says the complete wake-promoting mechanism is unknown. It does bind the dopamine transporter and inhibit dopamine reuptake, and a ten-man PET study measured transporter occupancy and higher extracellular dopamine after oral doses.
The PET result confirms human target engagement. It does not prove which circuit produces every clinical effect, predict an individual's benefit, or turn a mechanistic signal into evidence for broad cognition. The label also describes a pharmacologic profile that is not identical to amphetamine.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original source10 men · DAT occupancy and higher dopamine
Within-subject human PET mechanism study
Volkow ND et al. JAMA. 2009. PMID 19293415; PMCID PMC2696807.
Ten healthy men underwent PET after placebo and oral modafinil 200 mg or 400 mg. Both doses occupied dopamine transporters and increased extracellular dopamine in brain regions measured by the radiotracer method.
- Participants / model
- 10 healthy men
- Treatment
- Single oral modafinil 200 mg or 400 mg compared within person with placebo
- Follow-up
- Acute PET sessions
- Study design
- Open-label dose assignment with blinded radiotracer analysis and within-person placebo comparison
- Funding
- US National Institutes of Health and Department of Energy support
This measures target engagement in ten men, not clinical benefit, addiction incidence, or a complete wakefulness mechanism.
Read the original sourceWhy does any new rash need immediate attention?
Because a benign rash cannot be reliably distinguished early from a serious one. The label reports hospitalization and rare life-threatening SJS, TEN, DRESS, angioedema, anaphylaxis, and multi-organ hypersensitivity and says to stop at the first rash unless it is clearly not drug related.
- Nearly all serious-rash cases in the label occurred within one to five weeks, but later cases occurred too.
- Fever, mouth sores, blistering or peeling skin, facial or throat swelling, trouble breathing, jaundice, dark urine, or other organ symptoms raise the stakes.
- Stopping may not prevent a serious reaction from progressing, which is why the label calls for prompt medical assessment rather than watchful self-testing.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceWhich common and high-consequence effects matter in daily use?
Headache was common, 34 percent with modafinil versus 23 percent with placebo in the pooled trials. Nausea, nervousness, anxiety, insomnia, dizziness, and several other reactions were also more frequent, and 8 percent versus 3 percent discontinued for adverse reactions.
- Psychiatric: anxiety, agitation, insomnia, confusion, depression, mania, delusions, hallucinations, suicidal ideation, and aggression appear in trial or postmarketing labeling. Prior psychosis, depression, or mania warrants extra caution.
- Driving: wakefulness may remain abnormal even when someone feels better. The label calls for reassessment and avoidance of hazardous activity when sleepiness persists.
- Cardiovascular: chest pain, palpitations, dyspnea, ECG changes, blood-pressure treatment escalation, and rare serious events inform the label's monitoring advice in cardiovascular disease.
- Pregnancy: the label says animal data suggest fetal harm and human reports include growth restriction and spontaneous abortion, without adequate controlled pregnancy trials.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original source209 workers · modest benefit with residual impairment
Randomized double-blind placebo-controlled trial
Czeisler CA et al. New England Journal of Medicine. 2005. PMID 16079371.
In 209 adults with chronic shift-work sleep disorder, modafinil 200 mg before each night shift for three months increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo. CGI improvement was 74 versus 36 percent, attention lapses fell, and 29 versus 54 percent reported an accident or near accident on the commute home. Treated participants still had excessive sleepiness and impaired nighttime performance.
- Participants / model
- 209 adults with at least three months of diagnosed SWD, at least five night shifts monthly, objective sleepiness, and daytime insomnia
- Treatment
- Oral modafinil 200 mg or placebo before each night shift
- Follow-up
- 3 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon and National Institute for Occupational Safety and Health support; sponsor representatives helped design and analyze the study
The accident or near-accident outcome was self-reported. Multiple outcomes were tested, and the improvement did not normalize sleepiness or performance.
Read the original sourceHow does modafinil affect hormonal contraception?
Modafinil can induce CYP3A activity and reduce exposure to steroidal contraceptives. The label recommends an alternative or concomitant contraceptive method during use and for one month after stopping, including for depot or implantable steroidal contraception.
| Pathway or medicine | What can happen |
|---|---|
| CYP3A substrates | Steroidal contraceptives, cyclosporine, midazolam, and triazolam exposure or effectiveness may fall |
| CYP2C19 substrates | Phenytoin, diazepam, propranolol, omeprazole, and clomipramine exposure may rise |
| Warfarin | The label calls for more frequent prothrombin-time and INR monitoring |
| MAO inhibitors | The label advises caution with coadministration |
The roughly 15-hour effective half-life explains why timing can affect sleep, but enzyme effects and the one-month contraception precaution are separate pharmacology questions. One half-life calculation should not be used to shorten the label's interaction window.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceWhat does Schedule IV status mean for the benefit-risk discussion?
Modafinil remains a US Schedule IV controlled substance. The label describes psychoactive and euphoric effects, stimulant-like subjective effects, reinforcing behavior, and the need to watch for dose escalation and drug seeking, especially with prior stimulant or drug misuse.
Schedule IV status does not mean everyone develops addiction. The ten-man dopamine PET study shows biological plausibility for abuse potential but cannot estimate clinical misuse incidence.
eCFR · modafinil remains Schedule IV
Federal regulation
Electronic Code of Federal Regulations. 21 CFR 1308.14(f)(7).
The current Schedule IV stimulant list includes modafinil under DEA controlled-substance code 1680.
- Participants / model
- United States controlled-substance scheduling
- Treatment
- Not applicable
- Study design
- Federal regulation
Scheduling is jurisdiction specific. Other countries can classify or authorize modafinil differently.
Read the original sourceUS label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original source10 men · DAT occupancy and higher dopamine
Within-subject human PET mechanism study
Volkow ND et al. JAMA. 2009. PMID 19293415; PMCID PMC2696807.
Ten healthy men underwent PET after placebo and oral modafinil 200 mg or 400 mg. Both doses occupied dopamine transporters and increased extracellular dopamine in brain regions measured by the radiotracer method.
- Participants / model
- 10 healthy men
- Treatment
- Single oral modafinil 200 mg or 400 mg compared within person with placebo
- Follow-up
- Acute PET sessions
- Study design
- Open-label dose assignment with blinded radiotracer analysis and within-person placebo comparison
- Funding
- US National Institutes of Health and Department of Energy support
This measures target engagement in ten men, not clinical benefit, addiction incidence, or a complete wakefulness mechanism.
Read the original sourceWhy are modafinil and armodafinil not interchangeable names?
Modafinil is a 1:1 racemic mixture of R- and S-enantiomers. Armodafinil is the R-enantiomer sold as a separate drug. The R component clears more slowly, so the products have different exposure curves and their milligram strengths and trial results should not be swapped.
Modafinil acid and modafinil sulfone are metabolites and do not appear to contribute to the central wake-promoting action in the label. Product identity also matters for inactive ingredients and tablet strengths. Hypersensitivity to either modafinil or armodafinil is a Provigil contraindication.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceArmodafinil label · R-enantiomer product
FDA prescribing information
DailyMed. NUVIGIL (armodafinil) tablets. Label updated September 2, 2025.
The label identifies armodafinil as the R-enantiomer of racemic modafinil and supplies it in its own tablet strengths. It is a separate Schedule IV prescription product with its own exposure, dosing, efficacy, and safety record.
- Participants / model
- Adults covered by the Nuvigil product label
- Treatment
- Oral armodafinil tablets
- Follow-up
- Regulatory product record
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
Shared stereochemistry and warnings do not make milligram doses or trial results interchangeable.
Read the original sourcePubChem CID 4236 · chemical identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 4236, Modafinil.
The record identifies modafinil as C15H15NO2S, molecular weight 273.4 g/mol, CAS 68693-11-8, and CID 4236.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Chemical identity does not establish efficacy, formulation equivalence, or approval.
Read the original sourceWhich conclusions are secure, and which remain open?
Short-term wakefulness benefit in selected adults with narcolepsy, residual OSA sleepiness, and chronic SWD is established. The trials do not show that underlying OSA is treated, that alertness is normalized, or that rested healthy people get broad durable cognitive gains.
The strongest efficacy programs lasted four to twelve weeks or three months. One narcolepsy extension has been published, but open-label continuation cannot replace controlled long-term estimates for rare harms, misuse, cardiovascular outcomes, or sustained functional benefit. The Chinese OSA percentages remain filing-level evidence until a full protocol or report supplies missing definitions and denominators by arm.
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceeCFR · modafinil remains Schedule IV
Federal regulation
Electronic Code of Federal Regulations. 21 CFR 1308.14(f)(7).
The current Schedule IV stimulant list includes modafinil under DEA controlled-substance code 1680.
- Participants / model
- United States controlled-substance scheduling
- Treatment
- Not applicable
- Study design
- Federal regulation
Scheduling is jurisdiction specific. Other countries can classify or authorize modafinil differently.
Read the original sourcePubChem CID 4236 · chemical identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 4236, Modafinil.
The record identifies modafinil as C15H15NO2S, molecular weight 273.4 g/mol, CAS 68693-11-8, and CID 4236.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Chemical identity does not establish efficacy, formulation equivalence, or approval.
Read the original source271 adults · wakefulness improved, sleepiness returned
Randomized double-blind placebo-controlled trial
US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000. PMID 10720292.
In a 21-center trial, 271 modafinil-naive adults with narcolepsy received fixed oral modafinil 200 mg, 400 mg, or placebo for nine weeks; 240 entered a two-week discontinuation phase. Both objective sleep-latency measures, self-rated Epworth sleepiness, and clinician global change improved. Excessive daytime sleepiness returned to baseline after withdrawal, while amphetamine-like withdrawal symptoms were not reported in the two-week observation.
- Participants / model
- 271 adults with narcolepsy and objectively documented excessive daytime sleepiness
- Treatment
- Oral modafinil 200 mg, 400 mg, or placebo
- Follow-up
- 9 treatment weeks plus 2-week discontinuation phase
- Study design
- Randomized double-blind placebo-controlled 21-center trial
- Funding
- Cephalon program
The abstract does not provide every arm's absolute change. Return of sleepiness is not the same as a withdrawal syndrome, and two weeks cannot exclude every discontinuation effect.
Read the original source157 adults · ESS improved, objective normalization did not
Randomized double-blind placebo-controlled trial
Pack AI et al. American Journal of Respiratory and Critical Care Medicine. 2001. PMID 11719309.
In 157 adults with OSA and residual sleepiness despite regular effective CPAP, four weeks of modafinil improved Epworth Sleepiness Scale and mean sleep latency versus placebo. ESS normalized in 51 percent versus 27 percent. The proportion with a normal Multiple Sleep Latency Test did not differ, 29 percent versus 25 percent. Mean CPAP use stayed about 6.2 hours nightly in both groups.
- Participants / model
- 157 adults with OSA, residual sleepiness, and regular effective CPAP use
- Treatment
- Oral modafinil, 200 mg in week 1 then 400 mg in weeks 2 to 4, or placebo; CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon-associated pivotal program
The trial treated residual sleepiness after effective CPAP, not obstruction. It was short, and objective sleep-latency normalization was not significantly different.
Read the original source114 Japanese adults · residual sleepiness on optimal CPAP
Randomized double-blind placebo-controlled trial
Inoue Y, Takasaki Y, Yamashiro Y. Journal of Clinical Sleep Medicine. 2013. PMID 23946704.
At 37 Japanese sleep sites, 114 adults with residual sleepiness despite at least three months of adherent, effective nasal CPAP were randomized to oral modafinil 200 mg or placebo for four weeks. ESS changed by -6.6 versus -2.4, and the 50-person MWT subset changed by +2.8 versus -0.4 minutes. AHI and nocturnal polysomnography changed similarly between groups. Adverse drug reactions occurred in 36.5 versus 22.6 percent, a nonsignificant difference.
- Participants / model
- 114 Japanese adults with ESS at least 11, AHI at most 10 on CPAP, and documented CPAP adherence
- Treatment
- Oral modafinil 200 mg daily or placebo while nasal CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled 37-site trial
- Funding
- Alfresa Pharma supplied study medication and had employees among the authors
Only 50 participants underwent MWT. Four weeks and selected adherent CPAP users do not answer long-term outcomes or untreated OSA.
Read the original sourceChina dossier · 209-person OSA trial and formulation bridge
Public reimbursement submission citing regulatory review
Hunan Welman Pharmaceutical Co. Public submission for the 2022 National Reimbursement Drug List adjustment, filed July 14, 2022.
The Chinese-language public dossier says a 209-person randomized placebo-controlled domestic OSA sleepiness trial supported local review. It reports an 80.2 percent versus 45.0 percent composite response and 14.85 percent versus 3.00 percent 'recovery' rate. It also says 200 mg dispersible tablets, tablets, and capsules were bioequivalent and that only OSA was studied domestically, so the Chinese capsule indication was limited to wake promotion in adults sleepy from OSA.
- Participants / model
- 209 participants in a Chinese domestic OSA excessive-sleepiness trial; healthy Chinese volunteers in formulation pharmacokinetic studies
- Treatment
- Oral modafinil dispersible tablet versus placebo; separate bioequivalence comparisons among dispersible tablets, tablets, and capsules
- Follow-up
- Trial duration and arm allocation not stated in the public dossier excerpt
- Study design
- Sponsor reimbursement submission summarizing a randomized placebo-controlled trial and Chinese regulatory technical review
- Funding
- Submitted by Hunan Welman Pharmaceutical Co.; sponsor-authored public filing
The public dossier does not report arm sizes, duration, response definition, confidence intervals, attrition, or complete safety results. 痊愈 is translated as 'recovery,' but no operational definition is supplied.
Read the original source209 workers · modest benefit with residual impairment
Randomized double-blind placebo-controlled trial
Czeisler CA et al. New England Journal of Medicine. 2005. PMID 16079371.
In 209 adults with chronic shift-work sleep disorder, modafinil 200 mg before each night shift for three months increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo. CGI improvement was 74 versus 36 percent, attention lapses fell, and 29 versus 54 percent reported an accident or near accident on the commute home. Treated participants still had excessive sleepiness and impaired nighttime performance.
- Participants / model
- 209 adults with at least three months of diagnosed SWD, at least five night shifts monthly, objective sleepiness, and daytime insomnia
- Treatment
- Oral modafinil 200 mg or placebo before each night shift
- Follow-up
- 3 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon and National Institute for Occupational Safety and Health support; sponsor representatives helped design and analyze the study
The accident or near-accident outcome was self-reported. Multiple outcomes were tested, and the improvement did not normalize sleepiness or performance.
Read the original source54 healthy adults · severe deprivation, tiny arms
Randomized double-blind active- and placebo-controlled experiment
Killgore WDS et al. Aviation, Space, and Environmental Medicine. 2008. PMID 19238808; PMCID PMC2635585.
Fifty-four healthy adults stayed awake for 44 hours before receiving modafinil 400 mg (n=12), caffeine 600 mg (n=12), dextroamphetamine 20 mg (n=16), or placebo (n=14). All three active drugs supported vigilance and alertness. Modafinil and dextroamphetamine groups used fewer moves on the Tower of London task, while the modafinil group also deliberated longer. The relevant executive tasks had no rested baseline.
- Participants / model
- 54 healthy adults under 44 hours of total sleep deprivation
- Treatment
- Single oral modafinil 400 mg, caffeine 600 mg, dextroamphetamine 20 mg, or placebo
- Follow-up
- Single exposure with testing during roughly hours 45 to 50 awake
- Study design
- Randomized double-blind active- and placebo-controlled laboratory experiment
- Funding
- US Army Medical Research and Materiel Command
The modafinil arm had 12 people, the doses were high single exposures, and the design cannot answer routine rested use or long-term safety.
Read the original source64 rested adults · gains on some difficult tasks
Randomized double-blind placebo-controlled trial
Muller U et al. Neuropharmacology. 2013. PMID 22820554; PMCID PMC3485563.
Sixty-four non-sleep-deprived healthy adults received one oral 200 mg dose of modafinil or placebo. The modafinil group did better on the hardest levels of spatial working memory, planning, and decision tasks and on delayed visual pattern recognition, and reported greater task enjoyment. It did not improve paired-associate learning; overall mood did not change; creativity findings were inconsistent and nonsignificant.
- Participants / model
- 64 healthy non-sleep-deprived volunteers, 32 per group
- Treatment
- Single oral modafinil 200 mg or placebo
- Follow-up
- Single laboratory session
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
- Funding
- Wellcome Trust and Medical Research Council support; two authors reported industry relationships
This small, single-dose, multi-endpoint laboratory study did not measure sustained school or workplace output, daily function, or repeated-use safety.
Read the original source60 rested students · mostly null, limited task effects
Randomized double-blind placebo-controlled trial
Randall DC et al. Journal of Psychopharmacology. 2005. PMID 15738750.
Sixty healthy student volunteers aged 19 to 22 received a single 100 mg dose, 200 mg dose, or placebo. Several attention, spatial working-memory, long-term-memory, executive, visuospatial, and fluency tests were null. Some immediate verbal recall, visual recognition, sustained-attention, and color-naming outcomes differed, without a consistent dose pattern; 200 mg slowed pattern-recognition responses.
- Participants / model
- 60 healthy non-sleep-deprived students aged 19 to 22
- Treatment
- Single oral modafinil 100 mg, 200 mg, or placebo
- Follow-up
- Single laboratory session, testing two hours after dosing
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
Small arms and many cognitive endpoints increase the risk of unstable positive findings. A single laboratory session does not establish durable real-world enhancement.
Read the original source10 men · DAT occupancy and higher dopamine
Within-subject human PET mechanism study
Volkow ND et al. JAMA. 2009. PMID 19293415; PMCID PMC2696807.
Ten healthy men underwent PET after placebo and oral modafinil 200 mg or 400 mg. Both doses occupied dopamine transporters and increased extracellular dopamine in brain regions measured by the radiotracer method.
- Participants / model
- 10 healthy men
- Treatment
- Single oral modafinil 200 mg or 400 mg compared within person with placebo
- Follow-up
- Acute PET sessions
- Study design
- Open-label dose assignment with blinded radiotracer analysis and within-person placebo comparison
- Funding
- US National Institutes of Health and Department of Energy support
This measures target engagement in ten men, not clinical benefit, addiction incidence, or a complete wakefulness mechanism.
Read the original sourceArmodafinil label · R-enantiomer product
FDA prescribing information
DailyMed. NUVIGIL (armodafinil) tablets. Label updated September 2, 2025.
The label identifies armodafinil as the R-enantiomer of racemic modafinil and supplies it in its own tablet strengths. It is a separate Schedule IV prescription product with its own exposure, dosing, efficacy, and safety record.
- Participants / model
- Adults covered by the Nuvigil product label
- Treatment
- Oral armodafinil tablets
- Follow-up
- Regulatory product record
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
Shared stereochemistry and warnings do not make milligram doses or trial results interchangeable.
Read the original sourceStudies and sources
US label · three uses, safety, and interactions
FDA prescribing information
DailyMed. PROVIGIL (modafinil) tablets. Label updated December 31, 2022; prescribing information revised December 2022.
The label approves oral modafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder. It says OSA obstruction still needs treatment; gives disorder-specific trial results; and covers serious rash and hypersensitivity, persistent sleepiness, psychiatric and cardiovascular cautions, pooled common adverse reactions, driving, pregnancy, CYP interactions, Schedule IV status, abuse potential, racemic identity, mechanism, and pharmacokinetics.
- Participants / model
- Adults with excessive sleepiness associated with narcolepsy, OSA, or SWD; label safety database also includes other exposed groups
- Treatment
- Oral modafinil tablets
- Follow-up
- Regulatory product record and trials up to 12 weeks, with postmarketing reports
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
The DailyMed page was last updated in 2022 and is the active NDA label. Postmarketing reports cannot estimate incidence or prove causality.
Read the original sourceeCFR · modafinil remains Schedule IV
Federal regulation
Electronic Code of Federal Regulations. 21 CFR 1308.14(f)(7).
The current Schedule IV stimulant list includes modafinil under DEA controlled-substance code 1680.
- Participants / model
- United States controlled-substance scheduling
- Treatment
- Not applicable
- Study design
- Federal regulation
Scheduling is jurisdiction specific. Other countries can classify or authorize modafinil differently.
Read the original sourcePubChem CID 4236 · chemical identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 4236, Modafinil.
The record identifies modafinil as C15H15NO2S, molecular weight 273.4 g/mol, CAS 68693-11-8, and CID 4236.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Chemical identity does not establish efficacy, formulation equivalence, or approval.
Read the original source271 adults · wakefulness improved, sleepiness returned
Randomized double-blind placebo-controlled trial
US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000. PMID 10720292.
In a 21-center trial, 271 modafinil-naive adults with narcolepsy received fixed oral modafinil 200 mg, 400 mg, or placebo for nine weeks; 240 entered a two-week discontinuation phase. Both objective sleep-latency measures, self-rated Epworth sleepiness, and clinician global change improved. Excessive daytime sleepiness returned to baseline after withdrawal, while amphetamine-like withdrawal symptoms were not reported in the two-week observation.
- Participants / model
- 271 adults with narcolepsy and objectively documented excessive daytime sleepiness
- Treatment
- Oral modafinil 200 mg, 400 mg, or placebo
- Follow-up
- 9 treatment weeks plus 2-week discontinuation phase
- Study design
- Randomized double-blind placebo-controlled 21-center trial
- Funding
- Cephalon program
The abstract does not provide every arm's absolute change. Return of sleepiness is not the same as a withdrawal syndrome, and two weeks cannot exclude every discontinuation effect.
Read the original source157 adults · ESS improved, objective normalization did not
Randomized double-blind placebo-controlled trial
Pack AI et al. American Journal of Respiratory and Critical Care Medicine. 2001. PMID 11719309.
In 157 adults with OSA and residual sleepiness despite regular effective CPAP, four weeks of modafinil improved Epworth Sleepiness Scale and mean sleep latency versus placebo. ESS normalized in 51 percent versus 27 percent. The proportion with a normal Multiple Sleep Latency Test did not differ, 29 percent versus 25 percent. Mean CPAP use stayed about 6.2 hours nightly in both groups.
- Participants / model
- 157 adults with OSA, residual sleepiness, and regular effective CPAP use
- Treatment
- Oral modafinil, 200 mg in week 1 then 400 mg in weeks 2 to 4, or placebo; CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon-associated pivotal program
The trial treated residual sleepiness after effective CPAP, not obstruction. It was short, and objective sleep-latency normalization was not significantly different.
Read the original source114 Japanese adults · residual sleepiness on optimal CPAP
Randomized double-blind placebo-controlled trial
Inoue Y, Takasaki Y, Yamashiro Y. Journal of Clinical Sleep Medicine. 2013. PMID 23946704.
At 37 Japanese sleep sites, 114 adults with residual sleepiness despite at least three months of adherent, effective nasal CPAP were randomized to oral modafinil 200 mg or placebo for four weeks. ESS changed by -6.6 versus -2.4, and the 50-person MWT subset changed by +2.8 versus -0.4 minutes. AHI and nocturnal polysomnography changed similarly between groups. Adverse drug reactions occurred in 36.5 versus 22.6 percent, a nonsignificant difference.
- Participants / model
- 114 Japanese adults with ESS at least 11, AHI at most 10 on CPAP, and documented CPAP adherence
- Treatment
- Oral modafinil 200 mg daily or placebo while nasal CPAP continued
- Follow-up
- 4 weeks
- Study design
- Randomized double-blind placebo-controlled 37-site trial
- Funding
- Alfresa Pharma supplied study medication and had employees among the authors
Only 50 participants underwent MWT. Four weeks and selected adherent CPAP users do not answer long-term outcomes or untreated OSA.
Read the original sourceChina dossier · 209-person OSA trial and formulation bridge
Public reimbursement submission citing regulatory review
Hunan Welman Pharmaceutical Co. Public submission for the 2022 National Reimbursement Drug List adjustment, filed July 14, 2022.
The Chinese-language public dossier says a 209-person randomized placebo-controlled domestic OSA sleepiness trial supported local review. It reports an 80.2 percent versus 45.0 percent composite response and 14.85 percent versus 3.00 percent 'recovery' rate. It also says 200 mg dispersible tablets, tablets, and capsules were bioequivalent and that only OSA was studied domestically, so the Chinese capsule indication was limited to wake promotion in adults sleepy from OSA.
- Participants / model
- 209 participants in a Chinese domestic OSA excessive-sleepiness trial; healthy Chinese volunteers in formulation pharmacokinetic studies
- Treatment
- Oral modafinil dispersible tablet versus placebo; separate bioequivalence comparisons among dispersible tablets, tablets, and capsules
- Follow-up
- Trial duration and arm allocation not stated in the public dossier excerpt
- Study design
- Sponsor reimbursement submission summarizing a randomized placebo-controlled trial and Chinese regulatory technical review
- Funding
- Submitted by Hunan Welman Pharmaceutical Co.; sponsor-authored public filing
The public dossier does not report arm sizes, duration, response definition, confidence intervals, attrition, or complete safety results. 痊愈 is translated as 'recovery,' but no operational definition is supplied.
Read the original source209 workers · modest benefit with residual impairment
Randomized double-blind placebo-controlled trial
Czeisler CA et al. New England Journal of Medicine. 2005. PMID 16079371.
In 209 adults with chronic shift-work sleep disorder, modafinil 200 mg before each night shift for three months increased nighttime sleep latency by 1.7 minutes from baseline versus 0.3 with placebo. CGI improvement was 74 versus 36 percent, attention lapses fell, and 29 versus 54 percent reported an accident or near accident on the commute home. Treated participants still had excessive sleepiness and impaired nighttime performance.
- Participants / model
- 209 adults with at least three months of diagnosed SWD, at least five night shifts monthly, objective sleepiness, and daytime insomnia
- Treatment
- Oral modafinil 200 mg or placebo before each night shift
- Follow-up
- 3 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
- Funding
- Cephalon and National Institute for Occupational Safety and Health support; sponsor representatives helped design and analyze the study
The accident or near-accident outcome was self-reported. Multiple outcomes were tested, and the improvement did not normalize sleepiness or performance.
Read the original source54 healthy adults · severe deprivation, tiny arms
Randomized double-blind active- and placebo-controlled experiment
Killgore WDS et al. Aviation, Space, and Environmental Medicine. 2008. PMID 19238808; PMCID PMC2635585.
Fifty-four healthy adults stayed awake for 44 hours before receiving modafinil 400 mg (n=12), caffeine 600 mg (n=12), dextroamphetamine 20 mg (n=16), or placebo (n=14). All three active drugs supported vigilance and alertness. Modafinil and dextroamphetamine groups used fewer moves on the Tower of London task, while the modafinil group also deliberated longer. The relevant executive tasks had no rested baseline.
- Participants / model
- 54 healthy adults under 44 hours of total sleep deprivation
- Treatment
- Single oral modafinil 400 mg, caffeine 600 mg, dextroamphetamine 20 mg, or placebo
- Follow-up
- Single exposure with testing during roughly hours 45 to 50 awake
- Study design
- Randomized double-blind active- and placebo-controlled laboratory experiment
- Funding
- US Army Medical Research and Materiel Command
The modafinil arm had 12 people, the doses were high single exposures, and the design cannot answer routine rested use or long-term safety.
Read the original source64 rested adults · gains on some difficult tasks
Randomized double-blind placebo-controlled trial
Muller U et al. Neuropharmacology. 2013. PMID 22820554; PMCID PMC3485563.
Sixty-four non-sleep-deprived healthy adults received one oral 200 mg dose of modafinil or placebo. The modafinil group did better on the hardest levels of spatial working memory, planning, and decision tasks and on delayed visual pattern recognition, and reported greater task enjoyment. It did not improve paired-associate learning; overall mood did not change; creativity findings were inconsistent and nonsignificant.
- Participants / model
- 64 healthy non-sleep-deprived volunteers, 32 per group
- Treatment
- Single oral modafinil 200 mg or placebo
- Follow-up
- Single laboratory session
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
- Funding
- Wellcome Trust and Medical Research Council support; two authors reported industry relationships
This small, single-dose, multi-endpoint laboratory study did not measure sustained school or workplace output, daily function, or repeated-use safety.
Read the original source60 rested students · mostly null, limited task effects
Randomized double-blind placebo-controlled trial
Randall DC et al. Journal of Psychopharmacology. 2005. PMID 15738750.
Sixty healthy student volunteers aged 19 to 22 received a single 100 mg dose, 200 mg dose, or placebo. Several attention, spatial working-memory, long-term-memory, executive, visuospatial, and fluency tests were null. Some immediate verbal recall, visual recognition, sustained-attention, and color-naming outcomes differed, without a consistent dose pattern; 200 mg slowed pattern-recognition responses.
- Participants / model
- 60 healthy non-sleep-deprived students aged 19 to 22
- Treatment
- Single oral modafinil 100 mg, 200 mg, or placebo
- Follow-up
- Single laboratory session, testing two hours after dosing
- Study design
- Randomized double-blind placebo-controlled parallel-group trial
Small arms and many cognitive endpoints increase the risk of unstable positive findings. A single laboratory session does not establish durable real-world enhancement.
Read the original source10 men · DAT occupancy and higher dopamine
Within-subject human PET mechanism study
Volkow ND et al. JAMA. 2009. PMID 19293415; PMCID PMC2696807.
Ten healthy men underwent PET after placebo and oral modafinil 200 mg or 400 mg. Both doses occupied dopamine transporters and increased extracellular dopamine in brain regions measured by the radiotracer method.
- Participants / model
- 10 healthy men
- Treatment
- Single oral modafinil 200 mg or 400 mg compared within person with placebo
- Follow-up
- Acute PET sessions
- Study design
- Open-label dose assignment with blinded radiotracer analysis and within-person placebo comparison
- Funding
- US National Institutes of Health and Department of Energy support
This measures target engagement in ten men, not clinical benefit, addiction incidence, or a complete wakefulness mechanism.
Read the original sourceArmodafinil label · R-enantiomer product
FDA prescribing information
DailyMed. NUVIGIL (armodafinil) tablets. Label updated September 2, 2025.
The label identifies armodafinil as the R-enantiomer of racemic modafinil and supplies it in its own tablet strengths. It is a separate Schedule IV prescription product with its own exposure, dosing, efficacy, and safety record.
- Participants / model
- Adults covered by the Nuvigil product label
- Treatment
- Oral armodafinil tablets
- Follow-up
- Regulatory product record
- Study design
- Regulatory prescribing information
- Funding
- Manufacturer regulatory program
Shared stereochemistry and warnings do not make milligram doses or trial results interchangeable.
Read the original sourceWhy is Modafinil in A tier?
A reflects approved adult uses and controlled wakefulness trials in narcolepsy, treated obstructive sleep apnea, and shift-work disorder. Rested cognition, residual driving risk, armodafinil, and non-US formulations have separate evidence.
read Modafinil in the reptides guide, chapter 36: 8 pages, free to read.