What is modafinil (provigil)?

From the Guidelines

Modafinil is recommended as a first-line treatment for narcolepsy in adults due to its effectiveness in improving excessive daytime sleepiness, disease severity, and quality of life, as evidenced by a strong recommendation from the American Academy of Sleep Medicine 1.

Key Points About Modafinil

• Modafinil is a wakefulness-promoting agent used to treat excessive sleepiness caused by narcolepsy, shift work sleep disorder, and obstructive sleep apnea.
• The standard dosage is typically 200mg taken once daily, with some patients requiring 400mg daily or responding well to 100mg.
• Modafinil affects certain neurotransmitters in the brain, particularly dopamine, though its exact mechanism isn't fully understood.
• Side effects can include headache, nausea, nervousness, anxiety, insomnia, and rarely serious skin reactions.
• Modafinil may reduce the effectiveness of hormonal contraceptives, so alternative birth control methods should be considered.
• It has potential for abuse and dependency, though less than traditional stimulants.

Important Considerations

• Modafinil is contraindicated in patients with certain heart conditions and should be used cautiously in those with psychiatric disorders.
• While some use it off-label as a cognitive enhancer, this use isn't FDA-approved and carries risks without medical supervision.
• The medication is an FDA Schedule IV federally controlled substance due to its potential for abuse or dependency.
• Based on animal data, modafinil may cause fetal harm, and human data are insufficient to determine risk, making it essential to weigh the benefits and risks in pregnant and breastfeeding women 1.

Evidence Summary

The American Academy of Sleep Medicine recommends modafinil for the treatment of narcolepsy in adults based on moderate-quality evidence showing clinically significant improvements in excessive daytime sleepiness, disease severity, and quality of life 1. Although other studies have explored the use of modafinil for cancer-related fatigue and other conditions, the most recent and highest-quality evidence supports its use in narcolepsy. Therefore, modafinil should be considered a first-line treatment option for adults with narcolepsy, taking into account its potential benefits and risks 1.

From the FDA Drug Label

Modafinil tablets are a prescription medicine used to improve wakefulness in adults who are very sleepy due to one of the following diagnosed sleep disorders: narcolepsy obstructive sleep apnea (OSA). Modafinil tablets are used to treat excessive sleepiness, but not the obstruction or medical condition that is causing OSA Modafinil tablets will not cure these sleep disorders. Modafinil tablets may help the sleepiness caused by these conditions, but it may not stop all your sleepiness. Modafinil tablets do not take the place of getting enough sleep. Modafinil tablets are federally controlled substance (C-IV) because it can be abused or lead to dependence.

Modafinil is a prescription medicine used to improve wakefulness in adults with certain sleep disorders, including narcolepsy, obstructive sleep apnea (OSA), and shift work disorder (SWD). It is not a cure for these disorders and may not completely eliminate sleepiness.

• Key points:
  • Used to treat excessive sleepiness
  • Does not treat the underlying medical condition
  • May help with sleepiness but not cure the disorder
  • Does not replace getting enough sleep
  • Controlled substance due to potential for abuse or dependence 2
• Chemical information: Modafinil is a racemic compound with the chemical name 2-[(diphenylmethyl)sulfinyl]acetamide, molecular formula C15H15NO2S, and molecular weight 273.4 2

From the Research

Overview of Modafinil

• Modafinil is a wake-promoting agent approved for the treatment of excessive sleepiness associated with obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy 3, 4.
• It is recommended for use as an adjunct to standard therapies that treat the underlying airway obstruction in OSA 3.
• Modafinil has a novel mechanism of action, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate 5.

Clinical Uses of Modafinil

• Modafinil is effective in improving wakefulness, reducing sleepiness, and improving overall clinical condition in patients with OSA, SWD, and narcolepsy 3, 4.
• It has been shown to improve patient functioning, health-related quality of life, and nighttime and daytime sleep in patients with excessive sleepiness associated with SWD 6.
• Modafinil is also used off-label for the treatment of attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal, as well as an adjunct to antidepressants for depression 5.
• Additionally, modafinil has been used to manage fatigue associated with different conditions, including depression, cancer, and tiredness in military personnel 7.

Safety and Tolerability of Modafinil

• Modafinil is generally well tolerated, with a low abuse potential 3, 4.
• Common adverse events include headache and nausea 6.
• Modafinil does not adversely affect cardiovascular parameters or scheduled sleep 3.
• However, concerns have been raised about the potential for modafinil dependence, and further research is needed to characterize the long-term effects of the drug 7.

Pharmacology of Modafinil

• Modafinil is a wakefulness-inducing compound that produces positive outcomes in the management of fatigue associated with different conditions 7.
• It has been shown to improve memory and has cognitive-enhancing properties 7.
• The exact mechanisms of action of modafinil are not fully understood, but it is thought to work by increasing the levels of certain neurotransmitters in the brain, such as dopamine and norepinephrine 5.