What's The Difference Between Modafinil and Armodafinil?

Written on February 9, 2022 by | Reviewed by William Gallagher, MNeuroSci

Modafinil and armodafinil are both classified as eugeroics (or wakefulness-promoting agents), and are used for the treatment of narcolepsy, shift work sleep disorder, and other sleep disorders. The most significant difference between them is that armodafinil has a longer half-life than modafinil.

This means it can be taken once per day instead of twice a day, as in the case of modafinil. In addition, armodafinil is not highly addictive. Modafinil, on the other hand, has a moderate risk for drug abuse or addiction.

Armodafinil was approved for medical use in 2007, and is marketed in the United States as Nuvigil, manufactured by Cephalon Inc. Modafinil was first introduced into the market in 1998.

Modafinil vs. Armodafinil - How Do They Work?

The structure of armodafinil is similar to that of modafinil, with a few differences. For instance, armodafinil is not a racemate (it contains only a single enantiomer) and is pure R-modafinil. Armodafinil has fewer side effects than modafinil, hence its use by patients has been more common than that of modafinil.

Modafinil has an elimination half-life of 13 to 15 hours, while armodafinil's elimination half-life is 15 to 20 hours. Both compounds have short onset periods between 15 to 45 minutes after ingestion. The longer half-life in armodifanfil makes it easier to manage on a daily basis.

Modafinil directly acts as a stimulant and increases extracellular concentrations of dopamine, serotonin, and norepinephrine in the brain.

Armodafinil blocks monoamine reuptake transporters, which results in increased levels of dopamine, norepinephrine, and serotonin.

This increases wakefulness and reduces sleep onset latency: it is, therefore, effective in treating shift workers, those with impaired sleep-wake cycles due to jet lag or other disturbances, or those suffering from clinical disorders.

Modafinil has a high affinity for the dopamine (DAT) transporter in the human brain. Dopamine is released by nerve cells after stimulation.

However, it is also taken up by nerve cells by means of sodium-dependent dopamine (NaDAT) transporters inside the cells. NaDAT is specific for DAT rather than other transporter proteins that also act on dopamine (e.g., vesicular monoamine transporter).

Pharmacological blockade of DAT by drugs like cocaine causes a sudden rise in extracellular dopamine levels, causing severe psychomotor activation and hyperthermia leading to physical collapse.

In contrast, agents like modafinil exert their effects slowly through a long-term block of NaDAT leading to significant side effects such as drowsiness and loss of motor coordination, which are not usually caused by an increase in the dopaminergic activity itself.

Modafinil has been demonstrated to be effective against major depression when used at 400 mg/day for 6 weeks, with benefits seen after just 2 weeks of treatment. This benefit was not seen with shorter-term administration (<2 weeks).

The Difference In Effects On Mood

Modafinil has not been shown to have an effect on mood. It is, however, considered to be a cognitive enhancer and can be used for the treatment of ADHD, narcolepsy, and as a study aid.

Armodafinil does not have a significant effect on mood either. However, it is considered to be better than modafinil in treating ADHD since it does not cause blockage of the dopamine transporter (and hence the dopaminergic system) like modafinil.

This reduces the risk of side effects such as depressive mood that is caused by systemic blockade of dopamine transporters in patients with attention deficit hyperactivity disorder (ADHD).

Modafinil or Armodafinil: Which One Is Better?

There has been no head-to-head comparison between modafinil and armodafinil in clinical studies. Similarly, there is no information available on the bioavailability of armodafinil on the official manufacturers' website.

Preliminary pharmacokinetic data suggest that the bioavailability of armodafinil is similar to that of modafinil and better than that of D-amphetamine. The bioavailability of armodafinil is not affected by food and is independent of the patient's gender or age.

Therefore, if one was to compare modafinil with armodafinil, most scientific data available suggests that armodafinil would be the better alternative.

However, it should be noted that there are no head-to-head comparisons between the two medications because armodafinil was only approved by the FDA in 2007 while modafinil has been around since 1998. Since armodafinil would not have been compared to modafinil in any studies, it cannot be said for sure which one is better.

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135062/ (Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial)
  2. https://pubmed.ncbi.nlm.nih.gov/19663523/ (Armodafinil and modafinil half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies)
  3. https://pubmed.ncbi.nlm.nih.gov/26923035/ (Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials)
  4. https://www.webmd.com/drugs/2/drug-16962/modafinil-oral/details
  5. https://www.webmd.com/drugs/2/drug-148598/armodafinil-oral/details