Armodafinil vs. Modafinil | What’s the Difference?

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Armodafinil vs Modafinil

When it comes to the battle of Armodafinil vs. Modafinil, who emerges as the clear winner?

Both smart drugs seem to have a very similar name, but this doesn’t necessarily mean they have the same properties.

Yet the differences between the two nootropics may be so subtle to the point where your choice of nootropic really doesn’t matter.

Which leaves us stuck with several questions…

What are the differences between Modafinil and Armodafinil when it comes to their effectiveness? Does one last longer than the other? How about the side effects that come with either choice?

Is there a significant price difference in the Modafinil vs. Armodafinil comparison? Or are you only worried about a difference that amounts to pennies?

This definitive guide was written with the sole purpose of answering all those questions:

By the time you’re done reading, you’ll know everything there is to know about the Armodafinil vs. Modafinil debate. And which nootropic is the best one for you to take.

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This is not legal or medical advice. This article was strictly created for your entertainment. Please consult with your primary care physician or a medical professional with close working knowledge of your health -- before consuming pharmaceutical drugs or nootropics, like Modafinil. Please read my disclaimer.

What is Modafinil?

Most people already know about Modafinil, but in case this is your first time hearing about the smart drug, we’ll briefly catch you up to speed.

Modafinil is a Schedule IV prescription drug that was manufactured by Cephalon before they were bought out by Teva Pharmaceuticals. The United States Food and Drug Administration (FDA) approved Modafinil in 1998 under the brand name “Provigil” to treat excessive daytime sleepiness in the following conditions [1]:

  • Narcolepsy
  • Obstructive sleep apnea
  • Shift work sleep disorder

In doing so, Modafinil has helped millions of sleep-deprived people experience a better quality of life and function during the day without feeling fatigued.

But Modafinil is most famously known for its off-label use as a cognitive enhancer. And after several years of people in high-performance careers using the drug in this fashion (students, entrepreneurs, CEOs, surgeons, etc.), scientists investigated the drug even further [2]:

“…clinical studies have also documented beneficial effects of [Modafinil] on cognitive performance in human subjects who have been experimentally sleep deprived.”

“…[Modafinil] appears to also enhance cognitive performance in healthy adults who are not sleep-deprived.”
“Evidence for enhanced working memory, impulse control, vigilance and sustained attention in healthy volunteers has also been reported”

Modafinil’s primary effect involves the promotion of wakefulness and alertness, which is why it is classified as a “eugeroic”.
But in the Armodafinil vs. Modafinil battle, we have to appropriately introduce the other side…

What is Armodafinil?

Armodafinil, like Modafinil, is also a non-narcotic prescription drug that falls under Schedule IV and was manufactured by Cephalon. It was approved by the FDA in 2007 under the brand name, “Nuvigil” to treat the exact same problem as Modafinil, and for the same three medical conditions [3].

Armodafinil is best known as the R-(-)-enantiomer of Modafinil, as Modafinil is technically a racemic compound consisting of two separate enantiomers: The R-(-)-enantiomer and the S-(+)-enantiomer.

With Cephalon’s patent for Modafinil set to expire in 2015, meaning they would lose exclusive rights to manufacture and sell the drug, Cephalon needed a new drug to sustain profitability. They also did not want to lose their market dominance amongst the sleep-deprived population [4].

After rigorous testing, it was discovered that the R-(-)-enantiomer of Modafinil possessed the same properties as Modafinil itself.

Except it stays in your system for much longer and is believed by some to be more potent. This is a common tactic used in the pharmaceutical industry to maintain market dominance [5]:

“Chiral switching — substitution of a racemic drug with a single enantiomer in the marketplace, can confer advantage in maintaining a high market share even in the face of generic competition”

Armodafinil has also been studied for its fatigue-reducing effects, and some studies show great promise for this Modafinil spin-off [6].

So what does this mean for the Provigil vs. Nuvigil battle? Is there no difference experienced if you take either drug?

Armodafinil vs. Modafinil

Whether you want to compare Nuvigil vs. Provigil, or Armodafinil vs. Modafinil, it really doesn’t matter.

There are many more similarities between the two drugs than there are differences. The differences are mainly relevant for experienced smart drug users who are looking to further optimizing their cognitive enhancement.

Similarities

Provigil vs. Nuvigil are surprisingly alike when you compare the two. In fact, you’ll be much more hard-pressed to find any real differences between the two pharmaceutical medications.

  • Same Pharmacological Mechanism of Action

When it comes to Modafinil vs. Armodafinil, their exact mechanism of action for promoting wakefulness is still unknown to this day.

However, it appears as if both central nervous system (CNS) stimulants work in the same fashion. They stimulate localized regions of the brain instead of broadly activating the brain itself [7]:

“Both armodafinil and modafinil block dopamine reuptake by binding to the dopamine transporter and increasing dopamine concentrations in certain regions of the brain. However, dopamine receptor antagonists (e.g., haloperidol) and dopamine synthesis inhibitors (e.g., a-methyl-p-tyrosine) do not block modafinil’s action”

It is worth noting that unlike amphetamines and other traditional stimulants, there is a very low potential for dependency and abuse associated with either Armodafinil or Modafinil.

  • Affected by Food Intake

While taking food alongside your dose of Modafinil or Armodafinil will delay the onset of its effects by 1-2 hours, the overall bioavailability of both drugs remains unchanged [8, 9].

In other words, when it comes to Armodafinil vs. Modafinil, you will feel the effects “kick in” quicker when you take either smart drug without food.

  • Same Terminal Half-Life

The half-life of a drug can be defined as the time it takes for its concentration in the body to be reduced by 50%. If you are taking either Armodafinil or Modafinil, the terminal half-life is essentially the same at 13-15 hours [10]:

Despite similar half-lives, plasma concentrations following armodafinil administration are higher late in the day than those following modafinil administration on a milligram-to-milligram basis.

The different pharmacokinetic profile of armodafinil may result in improved wakefulness throughout the day in patients with ES compared with modafinil

We will expand upon this finding later in the “Differences” section.

  • Effectiveness in Treating Their Prescribed Conditions

There’s no competition in the Modafinil vs. Armodafinil debate regarding how well they can treat the conditions they were prescribed for.

A randomized double-blind clinical trial conducted across multiple centers in 2011 found they were equally effective in reducing excessive sleepiness brought about by shift work sleep disorder [11]:

“Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable.

The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg.

A 2016 meta-analysis involving the use of either Modafinil or Armodafinil also demonstrated equal effectiveness of both drugs in reducing daytime sleepiness within patients diagnosed with obstructive sleep apnea [12].

Both drugs clearly worked, possessed minimal side effects, and were well tolerated by patients.

  • Boosted Focus, Cognition, & Productivity

Finally, and most importantly, Armodafinil and Modafinil will provide the same cognition-enhancing effects. Here are the most common effects reported by thousands of test subjects [13]:

  • Improved short-term memory
  • Increased focus
  • Elevated confidence (i.e. more motivated)
  • Higher levels of alertness
  • Longer-lasting attention span

The only real competition in the Armodafinil vs. Modafinil discussion is which smart drug provides more of these effects, and which drug lasts longer. This tends to be very subjective and entirely dependent on the individual user.

Differences

Here’s where the Nuvigil vs. Provigil debate gets interesting, as many people will argue endlessly over the differences that exist between the two.
Yet as you are about to discover, the differences between Modafinil and Armodafinil are not very significant in number or scope.

  • Chemical Structure

As we stated previously, Modafinil is what’s known as a “racemic” mixture of two separate compounds [14]:

modafinil vs armodafinil

R-(-)-modafinil and S-(+)-modafinil are what are known as “enantiomers”. They have the same atoms, and the same 3D structure, but both molecules are non-superimposable mirror images of each other in the third dimension.

Here’s what we mean in simpler terms: Your hands are enantiomers of one another. Even though both are nearly identical in their structure, you cannot have the same ‘hand’ if you try to place your left hand on top of your right hand.

Modafinil contains both enantiomers. Armodafinil, on the other hand, purely consists of the “R” enantiomer. This is why it is commonly referred to as an “enantiopure” compound (and hence why the name “Armodafinil” is pronounced as “R-Modafinil”).

And while it may not seem like a big deal, these two enantiomers interact with your body’s enzymes in similar – yet different – ways.

  • Pharmacokinetic Properties

Remember the paper we quoted earlier that stated Armodafinil may lead to improved wakefulness?

This is where the Provigil vs. Nuvigil conversation starts to get interesting.

If you compare both enantiomers of Modafinil, the properties are quite different from one another:

  • The R-enantiomer has a half-life of 10-14 hours, while the S-enantiomer has a half-life of 3-4 hours [15]
  • The S-enantiomer has a three-fold shorter duration than the R-enantiomer, and is also eliminated 3x faster than the R-enantiomer [16]
  • The R-enantiomer has a three-fold higher affinity for the dopamine transporter than the S-enantiomer, and thus it is 3x more effective at inhibiting dopamine uptake [14]

Additionally, it is worth noting that the R-enantiomer is biologically active (i.e. exerts its effects) while the S-enantiomer is biologically inactive.

Notably, this does not contradict what we said earlier about the half-life of both drugs. While the effective half-life of Modafinil and Armodafinil are practically similar, the enantiomers themselves have significantly different half-lives.

And due to the fact that Armodafinil stays in your body for a longer period of time, it has a longer-lasting effect. Some researchers suggest the wakefulness effects are stronger in Armodafinil than Modafinil [17]:

“Relative to modafinil 200 mg, armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6-14 hours post-drug, and improved wakefulness and sustained attention for a longer time post-dose.”

Keep in mind a higher dose of Armodafinil was used, as the accepted rule of thumb is that 200 mg of Modafinil is equivalent to 150 mg of Armodafinil.

  • Dosing Regimen

The ideal Modafinil dosage and the ideal Armodafinil dosage are not the same.

However, the best dose to take for experiencing cognitive enhancement from either drug is highly similar to the one used for their prescribed conditions:

For Provigil (i.e. Modafinil), 200 mg once a day in the morning is the recommended dose for obstructive sleep apnea and narcolepsy. It comes in tablets of 100 mg or 200 mg.

For Nuvigil (I.e. Armodafinil), it’s 150 mg once a day in the morning for obstructive sleep apnea and narcolepsy. It comes in tablets of 50 mg, 150 mg, 200 mg, or 250 mg.

With both drugs, the dose is simply taken one hour before a work shift if the condition being treated is shift work sleep disorder.

While the maximum daily dose is well-tolerated for Armodafinil (250 mg daily) and Modafinil (400 mg), there are no additional benefits consistently proven beyond the recommended doses [18].

Side Effects and Safety Concerns

Armodafinil vs. Modafinil – which one is safer to take and comes with a lower frequency, and severity, of side effects? It turns out that both of them are virtually the same in this regard when it comes to safety [19]:

“…modafinil and armodafinil were effective and well tolerated by pediatric patients [<18 years old] with narcolepsy over a long period of clinical follow ups (up to 10 years). Concomitant administration of other psychopharmacological agents did not result in any significant side effects.

Use of modafinil and armodafinil significantly improved patient’s ability to stay awake and did not exacerbate preexisting psychiatric conditions”

Likewise, they have a very similar side effect profile [20]:

“Reported adverse events were mild to moderate in intensity. The most frequently reported adverse events while receiving armodafinil or modafinil were headache (29% and 2%, respectively), diarrhea (12% and 5%), nausea (10% and 2%), and dizziness (10% and 5%)”

Individuality and biochemical uniqueness will dictate if one suffers more side effects (severity and frequency wise) with Modafinil than Armodafinil (and vice versa).

There are a number of contra-indications with Armodafinil and Modafinil you should know about [21]:

Both drugs may reduce the effectiveness of medications lowering blood pressure (such as propranolol), as they slightly elevate blood pressure due to their stimulant properties

Both drugs will interfere with hormonal contraceptives and make them less effective, requiring alternative forms of birth control. They are “Category C” drugs and this means they may lead to developmental toxicity of the fetus in pregnant women [22]

Both drugs induce the enzymatic activity of CYP3A4 while inhibiting CYP2C19. Any drugs metabolized by these liver enzymes will have their concentrations reduced or increased (respectively), so make sure you read the product monographs associated with any co-administered medications [23, 24]

Please discuss any pre-existing issues you have with your doctor before taking either prescription drug (cardiovascular issues, mental health history, dysfunctional liver/kidney, etc.).

Armodafinil vs. Modafinil | Cost Comparison

If you do a price comparison of Provigil vs. Nuvigil, you’ll be shocked by how much each of them cost.

According to Drugs.com, here is what you can expect to pay if you purchase either drug from an actual pharmacy without insurance [25, 26]:

  • For 200 mg Provigil, you pay $24.64USD per pill. For generic Modafinil, the cost is lowered to $10.86USD per pill
  • For 150 mg Nuvigil, the cost goes up to $29.79 per pill. For generic Armodafinil, you can save a lot more by paying $6.88 per pill.

Therefore highly recommend buying the generic variant of these nootropics through a reputable and legitimate online Modafinil vendor like Buy Moda.

As per the generic variants, we would suggest going with Modalert for Modafinil and Waklert for Armodafinil. Both variants are manufactured by SUN Pharmaceuticals and are the highest-quality generics available on the market.

For either 150 mg Waklert or 200 mg Modalert, you will pay as little as $0.89-2.30USD per pill. The larger your order, the less you end up paying per pill [27].

If you are buying Armodafinil online or purchasing Modafinil online as we recommend, the price differences are very minimal.

As you’ll see in the next section, your selected winner in the Armodafinil vs. Modafinil fight really comes down to your personal preferences.

What Nootropic is Better?

Modafinil vs. Armodafinil… it seems like there’s virtually no difference between the two smart drugs.

This is the part of the conversation where anecdotal evidence and reports from test subjects come heavily into play.

Based on all the recommendations we have amassed to date, here is what we recommend in your choice of Provigil vs. Nuvigil.

The best way to test both drugs would be to get a sampler pack from your chosen online Modafinil vendor.

You will receive roughly two weeks supply of both Armodafinil and Modafinil to try out. This will be more than enough time to gauge the effectiveness of each nootropic.

You can observe how they affect your sleep (how easily you fall asleep, how easily you wake up, how interrupted your sleep is). But more importantly, you can assess the cognitive enhancement each one provides during the daytime.

While everyone will react to Armodafinil or Modafinil differently, some of the user reports seem to be fairly consistent with one another.

Modafinil has a shorter duration and acts faster, yet hits you “harder”. You may even experience a “feel-good” Modafinil high. To avoid sleep interference, take it no later than 10am.

Armodafinil leads to a longer-lasting boost in focus that feels “cleaner” and “smoother” but isn’t as pronounced. Some users claim they experience fewer jitters and less distractability. Thus, you will have to take it 1-2 hours earlier than you would Modafinil.

Regardless of which nootropic you pick, we do not advise taking them once a day for cognitive enhancement purposes. Daily dosing is only meant for people with the prescribed medical conditions.

Do not exceed 3 doses a week with either Modafinil or Armodafinil. You can choose to stick with one, or alternate between the two.

waklert armodafinil

Armodafinil vs. Modafinil | The Verdict

So what can we conclude from this extensive Armodafinil vs. Modafinil side-by-side comparison?

There is no real ‘winner’ here, as both Modafinil and Armodafinil work very well and have far more in common with each other.

Both smart drugs will give you the cognitive benefits you are looking for with little to no side effects.

The only major difference between both smart drugs is how you respond to them. Modafinil tends to provide a stronger boost in cognition that is shorter in duration, while Armodafinil provides a slightly weaker yet longer-lasting boost in cognition. The latter is better suited for regular, long-term usage.

But you don’t have to use one at the exclusion of the other. Try both of them out and see how we they work for you!

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References

  1. Hashemian SM, Farhadi T. A review on modafinil: the characteristics, function, and use in critical care. Jn Drug Assess. 2020;9(1):82-86. doi:10.1080/21556660.2020.1745209
  2. Mereu M, Bonci A, Newman AH, Tanda G. The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders. Psychopharmacology (Berl). 2013;229(3):415-434. doi:10.1007/s00213-013-3232-4
  3. Nishino S, Okuro M. Armodafinil for excessive daytime sleepiness. Drugs Today (Barc). 2008;44(6):395-414. doi:10.1358/dot.2008.44.6.1195861
  4. PROVIGIL Drug Profile. Retrieved June 13, 2020. drugpatentwatch.com
  5. Kakkar AK. Patent cliff mitigation strategies: giving new life to blockbusters. Expert Opin Ther Pat. 2015;25(12):1353-1359. doi:10.1517/13543776.2015.1088833
  6. McElhiney M, Rabkin J, Van Gorp W, Rabkin R. Effect of armodafinil on cognition in patients with HIV/AIDS and fatigue. J Clin Exp Neuropsychol. 2013;35(7):718-727. doi:10.1080/13803395.2013.823910
  7. Hegde S, Schmidt M. Chapter 28 – To Market, To Market – 2008. Annu Rep Med Chem. 2009;44:577-632. doi:10.1016/S0065-7743(09)04428-5
  8. PROVIGIL® (modafinil) Tablets [C-IV]. Retrieved June 12, 2020. accessdata.fda.gov
  9. Bogan RK. Armodafinil in the treatment of excessive sleepiness. Expert Opin Pharmacother. 2010;11(6):993-1002. doi:10.1517/14656561003705738
  10. Darwish M, Kirby M, Hellriegel ET, Robertson P Jr. 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):613-623. doi:10.2165/11315280-000000000-00000
  11. Tembe DV, Dhavale A, Desai H, et al. Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial. Neurol Res Int. 2011;2011:514351. doi:10.1155/2011/514351
  12. Kuan YC, Wu D, Huang KW, et al. Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials. Clin Ther. 2016;38(4):874-888. doi:10.1016/j.clinthera.2016.02.004
  13. Modafinil. Retrieved June 15, 2020. drugsand.me
  14. Loland CJ, Mereu M, Okunola OM, et al. R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012;72(5):405-413. doi:10.1016/j.biopsych.2012.03.022
  15. Primary Hypersomnia Treatment & Management. Retrieved June 14, 2020. emedicine.medscape.com
  16. Rapid onset and short term modafinil compositions and methods of use thereof. Retrieved June 13, 2020. patents.google.com
  17. 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. Curr Med Res Opin. 2006;22(1):159-167. doi:10.1185/030079906X80378
  18. Nuvigil® /armodafinil, Provigil®/modafinil – Prior Authorization with Quantity Limit Criteria Program Summary. Retrieved June 16, 2020. providers.bcbsal.org
  19. Ivanenko A, Kek L, Grosrenaud J. 0954 LONG-TERM USE OF MODAFINIL AND ARMODAFINIL IN PEDIATRIC PATIENTS WITH NARCOLEPSY. Sleep. 2017;40(suppl_1, 28):A354–A355. doi:10.1093/sleepj/zsx050.953
  20. Darwish M, Kirby M, D’Andrea DM, Yang R, Hellriegel ET, Robertson P Jr. Pharmacokinetics of armodafinil and modafinil after single and multiple doses in patients with excessive sleepiness associated with treated obstructive sleep apnea: a randomized, open-label, crossover study. Clin Ther. 2010;32(12):2074-2087. doi:10.1016/j.clinthera.2010.11.009
  21. NUVIGIL VS. PROVIGIL. Retrieved June 17, 2020. rxlist.com
  22. Provigil Birth Defects. Retrieved June 13, 2020. birthinjuryguide.org
  23. Rowland A, van Dyk M, Warncken D, Mangoni AA, Sorich MJ, Rowland A. Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol. Br J Clin Pharmacol. 2018;84(3):501-509. doi:10.1111/bcp.13478
  24. Darwish M, Kirby M, Robertson P Jr, Hellriegel ET. Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. doi:10.2165/00003088-200847010-00006
  25. Comparing Modafinil vs Provigil. Retrieved June 16, 2020. drugs.com
  26. Comparing Armodafinil vs Nuvigil. Retrieved June 16, 2020. drugs.com
  27. Buy Modafinil [Provigil] Online at BuyModa Generics. Retrieved June 17, 2020. buymoda.org

Table of Contents

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