Armodafinil vs Modafinil: Improvement or "Evergreening"?

Armodafinil vs Modafinil Verdict

Update 10/13/2016. My verdict is that armodafinil is an improvement on modafinil. Armodafinil feels “cleaner” and a lower dose is required.

But the now defunct ModafinilCat charges a little bit more for armodafinil (Brand names: Artvigil, Waklert). I prefer ordering Waklert from Sun pharma, as it seems to work a little better than Artvigil from HAB pharma. (If you find all these brand names confusing, see this handy comparison chart.)

Is armodafinil an example of pharmaceutical evergreening? Or is armodafinil an actual improvement on modafinil? Evergreening is the strategy where businesses extent their patents for products that are about to expire by tweaking them and re-patenting them.

The reason I ask is because armodafinil was developed just as modafinil’s patent expired.  This is quite common in the industry. The antidepressant Lexapro is another example. Comparing armodafinil vs modafinil, recognize that both drugs have extremely similar effects because armodafinil is derived from modafinil.

In this guide, we’ll compare armodafinil vs modafinil in terms of a number of parameters, and then discus whether armodafinil has any advantages over modafinil.

Armodafinil and modafinil are prescription wake-promoting agents. They’re used in the treatment of narcolepsy, obstructive sleep apnea-related sleepiness and shift work sleep disorders.

Both medications are increasingly being used by healthy subjects to enhance vigilance, mood and concentration in competitive work environments. While comparing armodafinil vs modafinil, it’s important to recognize that both drugs have been used to to treat ADHD, though they have not been approved for this purpose – they’re prescribed “off-label.”

Armodafinil vs Modafinil: What’s the Difference?

  • Chemistry. modafinil contains 50% r-modafinil (armodafinil) and 50% s-modafinil. Therefore, modafinil already contains 50% armodafinil – so you’ve already tried armodafinil if you’ve taken modafinil before.
  • Duration. Armodafinil lasts a few hours longer than modafinil. This is problematic for some users prone to insomnia.
  • Effects. Armodafinil and Modafinil have essentially identical effects in the brain
  • Potency. Armodafinil is a more expensive, purified and potent form of modafinil that requires a slightly lower dose (150mg vs 200mg)
  • Efficacy. There is no evidence that armodafinil is more effective than modafinil at their indicated doses. If you’re rolling in cash, you may want to shell out to get armodafinil instead of modafinil, but otherwise, it’s not worth it.
  • Date of FDA approval. Modafinil was discovered and used clinically prior to the introduction of armodafinil. Modafinil was approved by the FDA in 1998, whereas armodafinil was approved in June, 2007.

Chemical Differences Between Armodafinil and Modafinil

Armodafinil and modafinil are enantiomer molecules - they're mirror images of eachotherThere is an important chemical difference between armodafinil vs modafinil. Modafinil contains both R and the S enantiomers (mirror images) of the modafinil molecule. The mixture of both R and S enantiomers is said to be “racemic” because modafinil contains R- and S-modafinil in equal proportions (50%:50%).

In contrast, armodafinil contains only one enantiomer–R-modafinil–and is therefore said to be “enantiopure” (containing only a single enantiomer).

Loosely speaking, armodafinil can be thought of as a more purified form of modafinil, analogous to how the antidepressant Lexapro is a more purified version of Celexa. For this reason, the standard dose of modafinil is 200 mg whereas armodafinil only requires a dose of 150 mg.

Half-Life and Duration of Effects of Armodafinil vs Modafinil

Because R-modafinil has a half-life of 12-15 hours and S-modafinil has a half-life of 4 hours, many researchers expected to find that armodafinil (pure R-Modafinil) would have a longer half life in the body than modafinil (which contains 50% R-modafinil and 50% s-modafinil). However, one pharmacokinetic study which evaluated the absorption and clearance of both drugs found that the terminal half-life of modafinil vs armodafinil was approximately the same.  Many other studies suggest that armodafinil has a longer duration of action than modafinil, by a couple of hours.

The elimination profile of modafinil is biphasic, whereas armodafinil is monophasic, resulting in higher plasma drug concentrations from about 4-6 hours after armodafinil dosing onward.  Moreover, greater systemic availability (as indicated by markedly higher area under the curve values) was observed following armodafinil treatment compared with modafinil1.

Armodafinil also takes longer to reach peak concentration in serum than modafinil. It is thought that the enantiopure armodafinil may be more effective in treating excessive daytime sleepiness than racemic modafinil due to this delay in reaching peak serum concentrations.

Pharmacokinetics of Provigil vs Nuvigil

Mean (± standard error of the mean) plasma concentrations following doses of armodafinil 200 mg and modafinil 200 mg (pooled, dose-normalized data from studies 1 and 2 of armodafinil and from study 3 of modafinil) over the first 20 hours after administration, suggesting a monophasic elimination profile following armodafinil administration and a biphasic elimination profile following modafinil administration. Dotted lines 1 and 2 represent the different elimination rates of the S- and R-isomers of modafinil, respectively; dotted line 3 represents the elimination rate of armodafinil2.

Whether armodafinil exhibits superior therapeutic properties compared to modafinil or is an example of pharmaceutical evergreening remains controversial.

Both armodafinil and modafinil share the same mechanism of action. They enhance wakefulness by increasing the activity of catecholamines (dopamine and norepinephrine), and enhancing the release of other wake-promoting neurotransmitters and neuropeptides like orexin and histamine.

Armodafinil vs Modafinil: Safety Profile

Both armodafinil and modafinil have essentially the same safety profile due to their similarity in chemical structure. Both drugs are well-tolerated with few reports of adverse events.  Unlike Adderall (mixed amphetamine salts) and Ritalin (methylphenidate), modafinil and armodafinil have limited abuse potential due to their synergic effect on dopamine and histamine, and relatively low affinity for the dopamine transporter (DAT).

Armodafinil vs Modafinil Summary

  • Armodafinil is the purified (enantiopure) form of modafinil
  • Though armodafinil and modafinil have the same terminal half life, armodafinil reaches peak concentration later and has greater systemic availability. The effects of armodafinil may last longer than modafinil by a few hours.
  • The standard dose of armodafinil is 150 mg vs 200 mg for Modafinil
  • Armodafinil vs modafinil mechansim: both drugs have essentially identical mechanisms in the brain; the primary differences are pharmacokinetic (absorption, distribution, metabolism, excretion)
  1. Darwish M, Kirby M, Hellriegel ET, Robertson P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29(9):613-23. Link

  2. [ref][Darwish M, Kirby M, Hellriegel ET, Robertson P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29(9):613-23. Link.

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