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
• 2. Degradation of armodafinil
• 3. Interactions
• 4. Side effects, contraindication
  • 4.1. Side effects
  • 4.2. Contraindication
• 5. Armodafinil for ADHD

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

Tmax:

• 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

Metabolites:

• 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