Protocols by Charles Sieg

Medications

Nuvigil (armodafinil)

What the FDA label and the trials say about Nuvigil: what it is approved for, what it did in the pivotal trials, what is known about rested, healthy people, and the rash, sleep, and dependence cautions.

Overall evidence Mixed18 sourcesReviewed November 5, 2026

Placebo-controlled trials and a meta-analysis agree it modestly eases sleepiness from sleep apnea, narcolepsy, and shift work disorder, but in rested, healthy people the evidence is mostly single-dose modafinil studies with small, inconsistent effects.

The short version

  • I take Nuvigil. It is the brand name for armodafinil, a prescription drug the FDA approved to improve wakefulness in adults with excessive sleepiness from obstructive sleep apnea, narcolepsy, or shift work disorder1.
  • It is a Schedule IV controlled substance1.
  • In the 12-week pivotal trials, armodafinil added a few minutes on lab tests of staying awake or falling asleep, and more patients were rated improved than on placebo, for example 79% versus 59% in shift work disorder2,3,4.
  • For people who are not sleep-deprived, the studies tested modafinil, the closely related drug, and the pooled effect on thinking tests is small (g = 0.10 in one meta-analysis of 19 trials)5,6.
  • The label warns about serious rash, psychiatric symptoms, reduced effectiveness of hormonal contraceptives, and abuse and physical dependence1.

How I use it

I take Nuvigil. Everything else on this page is what the label and the trials used, not my routine.

The protocol

This is what the label and the trials used, not a prescription and not advice for anyone.

ParameterWhat the label and trials used
Approved usesExcessive sleepiness from obstructive sleep apnea, narcolepsy, or shift work disorder, in adults1
Label dose, sleep apnea or narcolepsy150 mg to 250 mg once a day in the morning1
Label dose, shift work disorder150 mg once a day, about one hour before the start of the work shift1
Doses in the label's trials150 mg and 250 mg in sleep apnea and narcolepsy, 150 mg in shift work disorder, each for 12 weeks1
Single doses in a healthy sleep-loss study100, 150, 200, and 300 mg, given once before a night of sleep loss7
Doses in the long-term extension50 to 250 mg a day; 57% (420 of 743) stayed on it for 12 months or more8
How long it stays in the bodyApparent terminal half-life of about 15 hours1
AgeNot approved for children for any indication1

In sleep apnea, the label says the drug treats the sleepiness and not the underlying obstruction1. The sleep apnea trials added it on top of CPAP in people already using CPAP4,9.

Status as of November 2026: the FDA's record for the drug (NDA 021875) shows its original approval on June 15, 200710. The label text I quote is the version DailyMed lists as current, posted May 7, 2025, which reads "Revised: 12/2022"1.

Why it works

Armodafinil is the R-enantiomer of modafinil: modafinil is a mix of two mirror-image forms, and armodafinil is the longer-lasting one9,1. The label says the mechanism by which it promotes wakefulness is unknown1.

In a trial of 107 healthy men kept awake through a night, single doses of armodafinil from 100 to 300 mg and modafinil 200 mg all lengthened the time they could stay awake and cut lapses on a vigilance task versus placebo (P < 0.0001). Armodafinil 200 mg and modafinil 200 mg reached comparable peak blood levels, but armodafinil's were higher 6 to 14 hours after the dose, and it kept people awake longer in that window7.

A small PET study of 10 healthy men found that modafinil at 200 mg and 400 mg blocked dopamine transporters and raised dopamine; binding of a tracer that marks those transporters fell 53.8% in the caudate and 39.3% in the nucleus accumbens11. That study tested modafinil, not armodafinil, and its authors call it a pilot.

What the research says

Moderate Shift work disorder. In a 12-week trial at 42 sleep research facilities, 254 night shift workers took armodafinil 150 mg or placebo 30 to 60 minutes before each night shift. On nap tests during laboratory night shifts, the average time to fall asleep rose from 2.3 to 5.3 minutes on armodafinil and from 2.4 to 2.8 minutes on placebo (P<.001), and 79% versus 59% were rated improved (P=.001)2. To enter the trial, people had to fall asleep in 6 minutes or less on that test, so even after treatment the group average still fell within the trial's own bar for excessive sleepiness2. It is one trial of one dose.

Moderate Narcolepsy. In a 12-week trial of 196 adults, armodafinil 150 mg (65 people) and 250 mg (67 people) lengthened the time to fall asleep on the Maintenance of Wakefulness Test by 1.3 and 2.6 minutes, while it shortened by 1.9 minutes on placebo (64 people), and 69% and 73% were rated at least minimally improved, versus 33%3.

Strong Obstructive sleep apnea, with CPAP in place. In a 12-week trial of 395 adults at 37 centers, 72% on armodafinil 150 or 250 mg were rated at least minimally improved, versus 37% on placebo4. A second 12-week trial of 259 patients on 150 mg found a 2.3-minute rise in wakefulness test latency versus a 1.3-minute fall on placebo (P=0.0003), with CPAP use unaffected9. A meta-analysis of 5 armodafinil trials (1,009 patients) and 11 modafinil trials (723 patients) found that, compared with placebo, the Epworth Sleepiness Scale improved by 2.63 points on armodafinil and 2.96 on modafinil, and wakefulness test latency lengthened by 2.71 and 2.51 minutes12.

Moderate Long-term use. An open-label extension of 743 patients (474 with treated sleep apnea, 113 with shift work disorder, and 156 with narcolepsy) found that 13% (95 of 743) stopped for adverse events in the first 12 months; the common ones were headache (25%), nasopharyngitis (17%), and insomnia (14%). Average blood pressure rose 3.6/2.3 mm Hg and heart rate 6.7 beats per minute8. It is one study with no placebo group, so it shows tolerability, not benefit.

Mixed Healthy people who are not sleep-deprived. This is the group most people mean by "smart drug," and the evidence is on modafinil, not armodafinil. A systematic review of studies through December 2014 found that most basic-test studies showed better executive function, only half showed better attention or learning and memory, a few showed worse divergent creative thinking, and more complex assessments consistently showed gains in attention, executive function, and learning6. A meta-analysis of 19 placebo-controlled single-dose trials (67 effect sizes) in adults who were not sleep-deprived, some of them psychiatric patients, found a small overall effect (g = 0.10, 95% CI 0.05 to 0.15) that did not differ between 100 mg and 200 mg, and concluded that modafinil has only limited potential as a cognitive enhancer outside sleep-deprived people5. Another meta-analysis of 14 modafinil studies in healthy, rested adults found an overall effect of 0.12 (p = .01) and a gain in memory updating of 0.28 (p = .03), and its authors say the belief that these drugs are effective cognitive enhancers is not supported by the evidence so far13. An earlier systematic review found modafinil improved attention in well-rested people, kept wakefulness, memory, and executive function up in sleep-deprived people, did not stop decline over a longer stretch of sleep loss, and may induce overconfidence in one's own performance14. None of these are armodafinil trials, and most are single-dose lab tests.

I found no placebo-controlled trial of armodafinil in healthy, well-rested adults that measured real-world work or training performance, so I am not claiming one.

Sleep

The label lists insomnia in 5% of Nuvigil patients versus 1% on placebo in its trials1. In the extension study, 14% reported insomnia8. A meta-analysis of modafinil studies found insomnia was far more likely than on placebo in sleep apnea (risk ratio 5.82) and in shift work sleep disorder (4.09)15. In the single-dose sleep-loss study, average sleep efficiency fell and average blood pressure rose7.

The label also warns that, even on treatment, a sleepy patient's level of wakefulness may not return to normal1.

Dependence and abuse

  • Label: it states that abuse of Nuvigil has been reported, that physical dependence can occur, and that multiple cases of tolerance were reported after approval1. Its abuse section rests on modafinil data: in an inpatient study of people experienced with drugs of abuse, modafinil produced psychoactive and euphoric effects consistent with methylphenidate, a scheduled stimulant1.
  • Brain imaging: in the 10-man PET study, modafinil blocked dopamine transporters and raised dopamine, including in the nucleus accumbens, and the authors called for heightened awareness of possible abuse and dependence in vulnerable people11.
  • Abuse-liability trials: in 24 men with a history of polysubstance abuse, modafinil at 200, 400, or 800 mg was told apart from placebo and liked, but it did not produce the significant response on the amphetamine scale that methylphenidate did16. In 12 people who used cocaine and completed a choice study, taking modafinil capsules at 200, 400, or 600 mg did not differ from taking placebo, and the authors concluded modafinil does not appear to have abuse liability in that group17.
  • The read: in these small studies, modafinil lacked methylphenidate's amphetamine-like signal and wasn't chosen over placebo, but people liked it and the label still reports abuse, dependence, and tolerance16,17,1. The people studied had drug-use histories and took modafinil. I did not find a large study of dependence on armodafinil in ordinary users.

Cautions

  • Serious rash. The label says to stop Nuvigil at the first sign of rash unless the rash is clearly not drug-related, to stop it if a multi-organ hypersensitivity reaction (DRESS) is suspected, and to stop it and report swelling of the face, eyes, lips, or tongue or trouble swallowing or breathing1.
  • Psychiatric effects. The label says to use particular caution in people with a history of psychosis, depression, or mania1. In the modafinil meta-analysis, anxiety or nervousness was more likely than on placebo in sleep apnea (risk ratio 3.26) and shift work sleep disorder (3.85)15.
  • Heart. The label says to use caution with known cardiovascular disease1. Blood pressure and heart rate rose slightly in the long-term study8.
  • Hormonal contraceptives. The label says steroidal contraceptives may be less effective during treatment and for one month after stopping, and it recommends another or an added method of contraception over that time1. The reason is enzyme induction: in 41 women on the pill, four weeks of modafinil caused a marked drop in blood levels of the test drug triazolam and a much smaller drop in ethinyl estradiol18.
  • Pregnancy. The label says the human data are insufficient to judge the risk, that intrauterine growth restriction and miscarriage have been reported with armodafinil and modafinil, and that animal studies showed developmental toxicity at clinically relevant exposures; it lists a pregnancy registry1.
  • Alcohol. The label says the combination with alcohol has not been studied and that it is prudent to avoid alcohol1.
  • Common side effects. In the label's placebo-controlled trials: headache 17% versus 9%, nausea 7% versus 3%, dizziness 5% versus 2%, and insomnia 5% versus 1%1.
  • A prescription drug. It is a controlled substance approved for the three conditions above, and whether it fits a person is a prescriber's call1.
  • Not covered here. I did not look for data on combining it with a multi-day fast like my monthly one, so this page says nothing about that.

References

  1. Cephalon, LLC. NUVIGIL (ARMODAFINIL) TABLET [CEPHALON, LLC]. DailyMed, National Library of Medicine (FDA-approved prescribing information), May 7, 2025.Regulatory noticeRead

    What it found: FDA-approved label for Nuvigil (armodafinil), a DEA Schedule IV drug indicated to improve wakefulness in adults with excessive sleepiness from obstructive sleep apnea, narcolepsy, or shift work disorder. It lists 150 mg to 250 mg once a day in the morning for sleep apnea or narcolepsy and 150 mg about one hour before a work shift for shift work disorder, an apparent terminal half-life of about 15 hours, and placebo-controlled adverse reactions of headache 17% versus 9%, nausea 7% versus 3%, dizziness 5% versus 2%, and insomnia 5% versus 1%. It warns of serious rash, DRESS, angioedema, psychiatric symptoms, and reduced effectiveness of steroidal contraceptives during treatment and for one month after stopping.

    Limits: A drug label, not a study; DailyMed lists this May 7, 2025 posting as current, and the label text itself reads Revised 12/2022.

  2. Czeisler CA, Walsh JK, Wesnes KA, Arora S, Roth T. Armodafinil for treatment of excessive sleepiness associated with shift work disorder: a randomized controlled study. Mayo Clinic Proceedings. 2009;84(11):958-972.Randomized trialPubMed 19880686 · DOI

    What it found: Twelve-week randomized controlled study at 42 sleep research facilities in North America of 254 permanent or rotating night shift workers with shift work disorder given armodafinil 150 mg or placebo 30 to 60 minutes before each night shift. Mean sleep latency on the MSLT rose from 2.3 to 5.3 minutes on armodafinil versus 2.4 to 2.8 minutes on placebo (P<.001), and 79% of armodafinil patients versus 59% of placebo patients improved on the clinical condition rating (P=.001).

    Limits: One dose (150 mg) in people diagnosed with shift work disorder, so it does not speak to healthy workers or other doses, and the final mean sleep latency of 5.3 minutes shows patients were still sleepy.

  3. Harsh JR, Hayduk R, Rosenberg R, Wesnes KA, Walsh JK, Arora S, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Current Medical Research and Opinion. 2006;22(4):761-774.Randomized trialPubMed 16684437 · DOI

    What it found: Twelve-week randomized trial in 196 adults with narcolepsy given armodafinil 150 mg (n = 65), 250 mg (n = 67), or placebo (n = 64) once daily. Sleep latency on the Maintenance of Wakefulness Test rose 1.3 minutes on 150 mg and 2.6 minutes on 250 mg but fell 1.9 minutes on placebo, and at least minimal clinical improvement was seen in 69% and 73% of the two armodafinil groups versus 33% on placebo (p < 0.0001).

    Limits: A 12-week trial in people with narcolepsy; the abstract gives no adverse event percentages or discontinuation figures, and the test gains are measured in minutes on a 20-minute test.

  4. Roth T, White D, Schmidt-Nowara W, Wesnes KA, Niebler G, Arora S, et al. Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clinical Therapeutics. 2006;28(5):689-706.Randomized trialPubMed 16861091 · DOI

    What it found: Twelve-week double-blind trial at 37 centers in the United States and Canada of 395 adults aged 18 to 65 with residual sleepiness despite nasal CPAP, given armodafinil 150 or 250 mg once daily or placebo. At the end, 72% of armodafinil patients versus 37% of placebo patients were rated improved on the Clinical Global Impression of Change.

    Limits: People kept using CPAP for the whole trial, so it shows armodafinil treats leftover sleepiness and does not treat the airway obstruction, and the abstract gives no discontinuation rates.

  5. Kredlow MA, Keshishian A, Oppenheimer S, Otto MW. The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis. Journal of Clinical Psychopharmacology. 2019;39(5):455-461.Meta-analysisPubMed 31433334 · DOI

    What it found: Meta-analysis of 19 placebo-controlled trials of single-dose modafinil with 67 effect sizes across attention, executive function, memory, and processing speed. The overall effect over placebo was small (g = 0.10, 95% CI 0.05 to 0.15, P < 0.001), dose (100 mg versus 200 mg) did not change it, and the authors conclude the evidence shows only limited potential for modafinil as a cognitive enhancer outside sleep-deprived people.

    Limits: Single-dose lab studies of modafinil, not armodafinil, and the abstract does not give participant numbers or per-domain results.

  6. Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. European Neuropsychopharmacology. 2015;25(11):1865-1881.Systematic reviewPubMed 26381811 · DOI

    What it found: Systematic review of MEDLINE studies from January 1990 to December 2014 of modafinil in healthy people who were not sleep-deprived. Most studies using basic tests found better executive function, only half found better attention or learning and memory, a few found worse divergent creative thinking, complex assessments consistently showed gains in attention, executive function, and learning, and the authors saw no preponderance of side effects or mood changes.

    Limits: The abstract gives no study counts, participant numbers, or doses, the review is of modafinil rather than armodafinil, and the studies were mostly short single-dose lab tests.

  7. Dinges DF, Arora S, Darwish M, Niebler GE. Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss. Current Medical Research and Opinion. 2006;22(1):159-167.Randomized trialPubMed 16393442 · DOI

    What it found: Double-blind randomized trial of 107 healthy men aged 18 to 40 given a single dose of armodafinil 100, 150, 200, or 300 mg, modafinil 200 mg, or placebo at 7:25 PM before a night of sleep loss. All armodafinil doses and modafinil increased wakefulness test latencies and reduced vigilance-task lapses versus placebo (P < 0.0001), and the reported adverse events included abdominal pain, nausea, headache, tachycardia or palpitations, lower mean sleep efficiency, and higher mean blood pressure.

    Limits: A single-dose study in healthy men kept awake through a night, so it shows what armodafinil does in sleep loss and says nothing about well-rested people or repeated use.

  8. 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: an open-label extension study. Journal of Clinical Sleep Medicine. 2010;6(5):458-466.Cohort studyPubMed 20957846 · DOI

    What it found: Open-label extension of four 12-week studies enrolling 743 patients (474 with treated sleep apnea, 113 with shift work disorder, and 156 with narcolepsy) on armodafinil 50 to 250 mg/day. About 57% (420/743) completed 12 months or more, discontinuations for adverse events were 13% (95/743), and the common adverse events were headache (25%), nasopharyngitis (17%), and insomnia (14%), with small average rises in blood pressure (3.6/2.3 mm Hg) and heart rate (6.7 beats per minute).

    Limits: Open-label with no placebo group, and people who tolerated the drug stayed in, so it shows tolerability over time and not how much of the benefit is the drug; the abstract gives no sleepiness scores.

  9. Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respiratory Medicine. 2007;101(3):616-627.Randomized trialPubMed 16908126 · DOI

    What it found: Twelve-week randomized double-blind study of 259 patients with obstructive sleep apnea/hypopnea syndrome and leftover sleepiness despite nasal CPAP, given armodafinil 150 mg once daily or placebo. Sleep latency on the Maintenance of Wakefulness Test rose 2.3 minutes on armodafinil and fell 1.3 minutes on placebo (P=0.0003), 71% versus 53% were rated improved (P=0.0069), and CPAP use was not adversely affected.

    Limits: A 12-week study at a single dose in CPAP-treated patients, so it cannot show long-term benefit or effects in people without sleep apnea.

  10. U.S. Food and Drug Administration. Drugs@FDA: NDA 021875, Nuvigil (armodafinil). Drugs@FDA, U.S. Food and Drug Administration, November 5, 2026.Regulatory noticeRead

    What it found: The FDA's Drugs@FDA record for new drug application 021875 shows the original Nuvigil approval on 06/15/2007 and labeling supplements dated 10/21/2010, 06/28/2013, 04/16/2015, and 02/07/2017.

    Limits: An approval and label index only; its label list ends at the 02/07/2017 supplement, so the label wording quoted on the page comes from DailyMed.

  11. Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA. 2009;301(11):1148-1154.Lab or mechanistic studyPubMed 19293415 · DOI

    What it found: Pilot PET imaging study of 10 healthy men given oral modafinil 200 mg and 400 mg. Dopamine transporter binding fell by 53.8% in the caudate, 47.2% in the putamen, and 39.3% in the nucleus accumbens, and raclopride binding fell 19.4% in the nucleus accumbens, so modafinil blocked dopamine transporters and raised dopamine, which the authors say calls for awareness of possible abuse and dependence in vulnerable people.

    Limits: Ten healthy men in a pilot imaging study of modafinil, not armodafinil, and brain imaging does not show whether anyone becomes dependent.

  12. Kuan YC, Wu D, Huang KW, Chi NF, Hu CJ, Chung CC. Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials. Clinical Therapeutics. 2016;38(4):874-888.Meta-analysisPubMed 26923035 · DOI

    What it found: Meta-analysis of 11 modafinil trials (723 patients) and 5 armodafinil trials (1,009 patients) in obstructive sleep apnea. Versus placebo, the Epworth Sleepiness Scale improved by 2.96 points on modafinil and 2.63 on armodafinil, and sleep latency on the Maintenance of Wakefulness Test lengthened by 2.51 and 2.71 minutes.

    Limits: Searched literature only through October 2015, and the abstract gives no doses or adverse event counts beyond saying both drugs were tolerated well.

  13. Roberts CA, Jones A, Sumnall H, Gage SH, Montgomery C. How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine. European Neuropsychopharmacology. 2020;38:40-62.Meta-analysisPubMed 32709551 · DOI

    What it found: Series of meta-analyses of 47 studies in healthy non-sleep-deprived adults. For modafinil (14 studies, 64 effect sizes) there was a small overall effect (SMD = 0.12, p = .01) and an improvement in memory updating (SMD = 0.28, p = .03), methylphenidate (24 studies) had an overall SMD of 0.21, and D-amphetamine (10 studies) showed no effects. The authors say the belief that these drugs are effective cognitive enhancers is not supported by the evidence so far.

    Limits: Acute single-dose lab studies in healthy adults and not armodafinil, and the abstract does not give participant numbers, so it cannot speak to long-term or real-world use.

  14. Repantis D, Schlattmann P, Laisney O, Heuser I. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacological Research. 2010;62(3):187-206.Systematic reviewPubMed 20416377 · DOI

    What it found: Systematic review of randomized trials in healthy people: in well-rested people modafinil improved attention, in sleep-deprived people it maintained wakefulness, memory, and executive function better than placebo, repeated doses did not prevent decline over a longer period of sleep deprivation, and modafinil may induce overconfidence in one's own performance. The authors say expectations about these drugs exceed the effects shown in trials.

    Limits: The abstract gives no study counts, participant numbers, or doses, and it covers modafinil, not armodafinil.

  15. Jung J, Youm J, Kang J, Kim AY, Suh JK, Kang HY. Assessing Condition-Specific Adverse Event Profiles of Modafinil for Labelled and Off-Label Uses: A Systematic Review and Meta-Analysis. Basic & Clinical Pharmacology & Toxicology. 2026;138(1):e70147.Meta-analysisPubMed 41367108 · DOI

    What it found: Systematic review and meta-analysis of 54 studies of modafinil. Versus placebo in sleep apnea, insomnia had a risk ratio of 5.82, anxiety or nervousness 3.26, and headache 1.92, and in shift work sleep disorder insomnia was 4.09, anxiety or nervousness 3.85, and nausea 2.93, so the specific risks vary across patient groups.

    Limits: About modafinil, not armodafinil, and the abstract does not give the number of randomized trials, participants, or discontinuation rates.

  16. Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. Journal of Psychopharmacology. 2000;14(1):53-60.Randomized trialPubMed 10757254 · DOI

    What it found: Double-blind Latin square crossover study of 24 men with a history of polysubstance abuse, including cocaine, given modafinil 200, 400, or 800 mg, methylphenidate 45 or 90 mg, or placebo. The men could tell both drugs from placebo and liked the effects of both, but modafinil showed no significant response on the Amphetamine Scale of the Addiction Research Center Inventory, unlike methylphenidate.

    Limits: Twenty-four men with drug-abuse histories taking single doses of modafinil, not armodafinil, so it says little about everyday use in people without that history, and the abstract does not report statistics.

  17. Vosburg SK, Hart CL, Haney M, Rubin E, Foltin RW. Modafinil does not serve as a reinforcer in cocaine abusers. Drug and Alcohol Dependence. 2010;106(2-3):233-236.Randomized trialPubMed 19783386 · DOI

    What it found: Double-blind randomized outpatient study in which twelve people who used cocaine (2 women, 10 men) completed three blocks of seven sessions, each block offering modafinil 200, 400, or 600 mg or placebo capsules. Choosing modafinil did not differ from choosing placebo, subjective ratings did not change systematically with dose, and the authors concluded that modafinil does not have abuse liability in people who use cocaine.

    Limits: Twelve people who already used cocaine, short outpatient sessions, and modafinil rather than armodafinil, with no statistics in the abstract.

  18. Robertson P Jr, Hellriegel ET, Arora S, Nelson M. Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clinical Pharmacology and Therapeutics. 2002;71(1):46-56.Randomized trialPubMed 11823757 · DOI

    What it found: Placebo-controlled single-blind study of 41 women on a long-term oral contraceptive containing ethinyl estradiol 0.035 mg, given modafinil 200 mg for 7 days then 400 mg for 21 days. Modafinil caused a marked drop in blood levels of the test drug triazolam and a much smaller drop in ethinyl estradiol, and the authors concluded that modafinil induces the CYP3A4/5 enzymes in humans.

    Limits: Tested modafinil, not armodafinil, in a small single-blind study, and the abstract gives no percentages for the change in ethinyl estradiol.