Wake Up and Smell the Modafinil

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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.

Cautions
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.

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


REFERENCES

  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.

ABOUT THE AUTHORS

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.

2 Comments

  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.

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