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Armodafinil for ADHD


Armodafinil for ADHD

Armodafinil is a stimulant.
It is clearly different from amphetamines.
Amordafinil is the (R)-enantiomer of the racemate modafinil.

Other names:1

  • C15H15NO2S
  • (-)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide
  • (-)-(R)-modafinil
  • (-)-modafinil
  • (R)-(-)-modafinil
  • (R)-modafinil
  • Armodafinil
  • Armodafinilo
  • Armodafinilum
  • R-modafinil
  • CEP 10953
  • CEP-10952
  • CEP-10953
  • CRL 40982
  • CRL-40982

Armodafinil has been approved in the USA since 2007 for the treatment of

  • excessive daytime sleepiness in adults with obstructive sleep apnea
  • Narcolepsy
  • Shift worker syndrome

US patent protection ends in 2023.

Brand name: Nuvigil®

1. Mechanisms of action of armodafinil

The exact mechanism of action is unknown1
Armodafinil belongs to the stimulant class of eugeroics. These cause a long-lasting mental arousal.
It activates the sympathetic nervous system.
Armodafinil does not bind to or inhibit any receptors or enzymes that control sleep-wake regulation.
Armodafinil works neither directly nor indirectly

  • as a dopamine receptor agonist
  • as an α1-adrenoceptor agonist

Armodafinil (like modafinil) binds to the DAT and acts as a dopamine reuptake inhibitor (stronger than modafinil).23


  • if taken without food after 2 hours
  • when taken with food after 4 to 6 hours

2. Degradation of armodafinil

Half-life: 15 hours

Armodafinil is broken down by

  • CYP3A4/5 (second most important degradation pathway)
  • hydrolytic deamidation (most important degradation pathway)
  • S-oxidation
  • Hydroxylation of the aromatic ring with subsequent glucuronide conjugation of the hydroxylated products


  • R-Modafinilic acid
  • Modafinil sulfone

3. Interactions

  • Grapefruit juice
  • St. John’s wort
  • oral contraceptives
  • Anticonvulsants
  • Anticoagulants (anticoagulants)
  • Ciclosporin (an immunosuppressant)

Inductor from

  • CYP3A4 (weak)
  • CYP3A5 (strength unknown)
  • CYP1A2 (strength unknown)
  • CYP2B6 (strength unknown)

Inihbitor from

  • CYP2C19 (moderate)
  • CYP2C9 (strength unknown)

4. Side effects, contraindication

4.1. Side effects

  • Headache
  • Nausea
  • Dizziness
  • Sleep disorders
  • mild allergic reactions
    • Skin rashes
    • Hay fever

Severe allergic skin reactions are possible.

4.2. Contraindication

The dose should be reduced in the case of severe hepatic or renal insufficiency

5. Armodafinil for ADHD

Armodafinil could be helpful in the treatment of ADHD in adults.
A meta-analysis of 86 studies4 found that in adults with sleep disorders and other illnesses, acute and chronic administration improved

  • Alertness
  • Memory
  • Impulse control
  • Executive functions

In addition, there were indications of an improvement in

  • cognitive functions
  • Mood swings

Another meta-study found 4 studies with n = subjects that investigated armodafinil in ADHD.5

  1. Armodafinil bei

  2. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH (2012): R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012 Sep 1;72(5):405-13. doi: 10.1016/j.biopsych.2012.03.022. PMID: 22537794; PMCID: PMC3413742.

  3. Keighron JD, Quarterman JC, Cao J, DeMarco EM, Coggiano MA, Gleaves A, Slack RD, Zanettini C, Newman AH, Tanda G (2019): Effects of ( R)-Modafinil and Modafinil Analogues on Dopamine Dynamics Assessed by Voltammetry and Microdialysis in the Mouse Nucleus Accumbens Shell. ACS Chem Neurosci. 2019 Apr 17;10(4):2012-2021. doi: 10.1021/acschemneuro.8b00340. PMID: 30645944; PMCID: PMC8294083.

  4. Lamas-Aguilar R, Diaz-Ruiz A, Navarro L, Miranda-Ojeda R, Martínez-Cárdenas MLÁ, Mata-Bermudez A, Rios C (2024): Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review. Curr Neuropharmacol. 2024 Mar 14. doi: 10.2174/1570159X22666240131121642. PMID: 38486390. METASTUDY

  5. Miskowiak KW, Obel ZK, Gugliemo R, Bonnin CDM, Bowie CR, Balanzá-Martínez V, Burdick KE, Carvalho AF, Dols A, Douglas K, Gallagher P, Kessing LV, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes PRA, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Young AH, Vieta E, Hasler G (2024): Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force. Bipolar Disord. 2024 Mar 3. doi: 10.1111/bdi.13414. PMID: 38433530. REVIEW

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