Wake Up and Smell the Modafinil


Eugeroics offer a costly—but effective—alternative to caffeine for the sleep deprived.

We all struggle with night shifts. The 4 a.m. mental fog that descends on everyone can make it difficult to focus on managing the minute-but-critical details of a department full of patients. Wouldn’t it be great if there were a way to clear that fog and process information as well as you do during the light of day?

While coffee is our usual go-to, it comes with unpleasant, jittery side effects. There may be a better way. It turns out there is a class of medications that have been used for years for narcolepsy, daytime sleepiness caused by OSA, and for shift work sleep disorder (SWSD). Modafinil and armodafinil are eugeroics (wakefulness-promoting agents) that have been used by the military, astronauts, and  physicians [1]. Modafinil (Provigil) first came on the US market in 1998 for narcolepsy and was FDA-approved for night shift work and for OSA-related sleepiness in 2003. Armodafinil (Nuvigil) is the pure R-enantiomer of modafinil and was approved in 2007.


A dose of modafinil is about as strong as 600mg of caffeine [2] the equivalent of about two grande coffees, but does not induce the shakiness, feelings of anxiety, or frequent trips to the bathroom that excessive caffeine can.

Other stimulants, such as amphetamines (Adderall) and methylphenidate (Ritalin), are controlled substances and can be habit-forming. They also have many potential side effects such as psychosis, depression, and irritability. By contrast, modafinil appears to promote wakefulness with minimal side effects, without inducing tolerance, and with low abuse and addiction potential.

While these medications are sometimes referred to as “neuro-enhancers,” they will not make you as smart as Matt Damon’s character in Good Will Hunting. However, they can elevate your cognitive function closer to your own non-sleep-deprived state [3,4]. In a 2012 study of healthy male physicians who had been sleep deprived for one night, those who took modafinil performed better on tests of higher cognitive function, solved  problems that required the use of planning and working memory more efficiently, and made less impulsive decisions [5]. However, in a 2014 systematic review of 24 studies of healthy (rested) subjects, modafinil appeared to improve executive function, attention, learning, and memory without consistent negative effects [6].


Should medical personnel working on little to no sleep take this drug? Is it a good choice for patients that regularly burn the midnight oil? If you were in the ED as a patient at 3 a.m., would you want your doctor to be on a eugeroic? Leave a comment online or send your thoughts in to the editors.

How it works
The full mechanism is not clear, but modafinil binds to the dopamine transporter (DAT) and inhibits dopamine reuptake, directly raising cerebral catecholamines and indirectly lowering GABA (among other effects).

Major indications and doses
Modafinil is used for patients with narcolepsy and daytime sleepiness from OSA, given once daily in the morning. For night shift workers, modafinil is used at a 200mg dose 1 hour prior to starting the shift. Armodafinil is used at 150mg 1 hour prior to the night shift [7].

Recently in the news for
In the United States, modafinil is a Schedule IV controlled substance. It requires a prescription. This is definitely not a medication you should prescribe for yourself or your co-workers! In 2004 it was added to the list of prohibited substances for athletes.


Adverse events
Side effects are usually mild and may include headaches, difficulty falling asleep (that’s kind of the point), anxiety, nausea, dizziness, and xerostomia.

Modafinil is pregnancy class C. It is not recommended for breast-feeding mothers, as agents that increase dopamine levels can inhibit prolactin and therefore reduce milk production. In addition, modafinil is a small, lipophilic molecule and is likely to cross into breastmilk [8]. Modafinil is a substrate of the CYP3A4 enzyme, so it has many potential drug-drug interactions, including with some opiates, benzodiazepines, calcium channel blockers, and SSRIs.

Certainly not cheap. Modafinil costs a whopping $1000 for 30 200mg tablets. 30 tablets of 150mg armodafinil is about $6567.


  1. Westcott KJ. Modafinil, sleep deprivation, and cognitive function in military and medical settings. Mil Med. 2005;170(4):333-335.
  2. Davies M. Is it clever for doctors to take smart drugs? BMJ Careers Web site. http://careers.bmj.com/careers/advice/Is_it_clever_for_doctors_to_take_smart_drugs%3F#ref5. Published 01/18/2016. Updated 2016. Accessed 11/09, 2016.
  3. Repantis D, Schlattmann P, Laisney O, Heuser I. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacol Res. 2010;62(3):187-206.
  4. Wesensten NJ. Effects of modafinil on cognitive performance and alertness during sleep deprivation. Curr Pharm Des. 2006;12(20):2457-2471.
  5. Sugden C, Housden CR, Aggarwal R, Sahakian BJ, Darzi A. Effect of pharmacological enhancement on the cognitive and clinical psychomotor performance of sleep-deprived doctors: A randomized controlled trial. Ann Surg. 2012;255(2):222-227.
  6. Battleday, R.M. et al. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. European Neuropsychopharmacology. 2014;25(11):1865 – 1881
  7. Lexicomp Online. Modfainil: Drug information<br />Armodafinil: Drug information. www.uptodate.com. Accessed 11/09, 2016.
  8. Hale TW. Medications and mothers’ milk: A manual of lactational pharmacology. 12th ed. Amarillo, TX: Hale Publishing L.P.; 2012:1331.


Dr. Shenvi is an assistant professor in the department of emergency medicine at the University of North Carolina. She authors RX Pad each month in EPM.

Karen Serrano, MD is an assistant professor in the department of emergency medicine at the University of North Carolina.


  1. Not sure where you got your pricing from, but generic modafinil is listed in the $100-$150 range for 30 tablets on GoodRx.com. …so at about $3-5/pill it may be cheaper than your cup of Starbucks.

    • I’m a M.S patient and I take Modafinal for fatigue and brain fog and depression and I believe it has pain reducing properties So. I pay 20 Dollars for 60 200 mg tablets with my social security plan through Atrio . Do the math that turns out to about 33.3 cents a tablet much cheaper than a cup of Starbucks coffee. I know different people experience different benefits using modafinal this is my personal experience only I’ve talked to other M.S patients that say it didn’t help them at all so this isn’t a Modafinal promo post.

  2. On GoodRx today, the price at Lucky Pharmacy (big chain grocery store) for 30 tablets, 200 mg is $23.70 and at Walmart is $37.98

    Christina, you won’t get away with just blithely saying that there’s “some” variability in pricing.

    The prices on GoodRx (a free app that ton’s of people use) are 96-97% than the inflated ones you quote. Put another way, the absurd price you put in this article is 26 to 38 TIMES higher than the actual prices today. You owe it to your readers to amend with current/valid info, as neither the articile nor uptodate.com are actually “up to date.”

  3. I take modafinil to treat narcolepsy. I found adderall and methylphenidate to be difficult to tolerate due to constant energy soars and crashes. Additionally, shortages of those medication would mean sometimes I’d go days without them forcing me into withdrawal. I am much happier in modafinil. However, before the big tort lawsuit about price gouging (I did receive a settlement), I have had to pay in excess of $30 per tablet for it about 10 years ago or so (hence the big lawsuit). All in all, it is a great medication for my narcoleptic condition and preferable to shorter-acting and stronger stimulants.

  4. I would like to mention also that another reviewer accused the writers of listing “absurd price[s]” for the medication and as a recipient of settlement money from the pharmaceutical company I can tell you that they are NOT wrong. I’d also advise readers to remember that pharmacies may decline to accept coupons and GoodRx pricing. Pre-lawsuit this medication was $30-40 per tablet. Luckily, my insurance is covering it now.

  5. There’s a lot of misconception regarding modafinil. Alot of self reports and very bias reviews.

    I have taken the drug for about 5 years on a daily basis. Even today little is known about the drug but there’s enough to make an educated guess on what it does to our neurotransmitters and body. It’s just that the internet will continue to spread mis/disinformation. I mean smoking was considered safe in the 50s due to the lack of evidence.. and yet 50 years later even the dumbest of minds can’t deny the effects of smoking.

    Taking modafinil is the biggest regret in my life. I’m 1 year removed from the drug and I still don’t feel myself. It is compared to caffeine or even something slight above caffeine (whatever that even means). This is false. It’s not caffeine at all. It’s not a caffeine alternative at all. It’s pretty much a stimulant like adderalls and cocaine but with far less abuse potential. But that doesn’t mean it’s safer because the potential to abuse is still there.

    While I was on modafinil I lost my friends.

    Within the year of withdrawal, I have lost my job, lost my savings, and moved in with my parents. It’s been a year and I still don’t have the motivation to move out. It’s gradually improving but it’s extremely difficult to even get out of bed sometimes.

    This drug was doing something to my brain during those 5 years and when I decided to cold turkey my brain went into complete shock. Total opposite of what the popular belief is.

    My advice from this experience. Stay off the internet in regards to prescription drugs, drugs in general,and any information related to your health and wealth

    • Thank you for your reply. I have been back and forth with Modafinil and Mydayis for the last 6 months. Where as modafinil keeps me awake but the Mydayis helps with my ADHD. I really didn’t know which one to take but I switched back to Mydayis( the newest form of Adderall ). Thank you for your comment.

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