Modafinil, sold under the brand name Provigil among others, is a medication to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea. While it has seen off-label use as a purported cognitive enhancer, the research on its effectiveness for this use is not conclusive. It is taken by mouth.
Common side effects include headache, anxiety, trouble sleeping, and nausea. Serious side effects may include allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, misuse, and hallucinations. It is unclear if use during pregnancy is safe. The amount of medication used may need to be adjusted in those with kidney or liver problems. It is not recommended in those with arrhythmia, significant hypertension, or left ventricular hypertrophy. How it works is not entirely clear. One possibility is that it may affect the areas of the brain involved with the sleep cycle.
Modafinil was approved for medical use in the United States in 1998. In the United States it is classified as a schedule IV-controlled substance. In the United Kingdom it is a prescription-only medication. It is available as a generic medication. In the United Kingdom it costs the NHS about £105.21 a month as of 2018. In the United States the wholesale cost per month is about US$34.20 as of 2018. In 2016, it was the 284th most prescribed medication in the United States, with more than a million prescriptions.
Modafinil is a eugeroic used for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea.
For obstructive sleep apnea, it is recommended that continuous positive airway pressure be appropriately used before considering starting modafinil to help with daytime sleepiness.
Because of the risk for the development of skin or hypersensitivity reactions and serious adverse psychiatric reactions, the European Medicines Agency has recommended that new patient prescriptions should be only to treat sleepiness associated with narcolepsy.
Armed forces of several countries, including the United States, the United Kingdom, India and France, have expressed interest in modafinil as an alternative to amphetamine—the drug traditionally employed in combat situations or lengthy missions where troops face sleep deprivation. The French government indicated that the Foreign Legion used modafinil during certain covert operations. The United Kingdom’s Ministry of Defence commissioned research into modafinil from QinetiQ and spent £300,000 on one investigation. In 2011, the Indian Air Force announced that modafinil was included in contingency plans.
In the United States military, modafinil has been approved for use on certain Air Force missions, and it is being investigated for other uses. As of November 2012, modafinil is the only drug approved by the Air Force as a “go pill” for fatigue management (replacing prior use of amphetamine-based medications such as dextroamphetamine).
The Canadian Medical Association Journal also reports that modafinil is used by astronauts on long-term missions aboard the International Space Station. Modafinil is “available to crew to optimize performance while fatigued” and helps with the disruptions in circadian rhythms and with the reduced quality of sleep astronauts experience.
Adverse effects and contraindications
Modafinil is contraindicated in people with known hypersensitivity to modafinil, armodafinil, or inactive ingredients. Modafinil is not approved for use in children for any medical conditions.
The incidence of adverse effects is reported as the following: less than 10% of users report having a headache, nausea, and decreased appetite. Between 5% to 10% of users may be affected with anxiety, insomnia, dizziness, diarrhea, and rhinitis.
Rare occurrences have been reported of more serious adverse effects, including severe skin rashes and other symptoms that are probably allergy-related. From the date of initial marketing, December 1998, to January 30, 2007, the US Food and Drug Administration received six cases of severe cutaneous adverse reactions associated with modafinil, including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome, involving adult and pediatric patients. The FDA issued a relevant alert. In the same alert, the FDA also noted that angioedema and multi-organ hypersensitivity reactions have also been reported in postmarketing experiences. In 2007, the FDA ordered Cephalon to modify the Provigil leaflet in bold-face print of several serious and potentially fatal conditions attributed to modafinil use, including TEN, DRESS syndrome, and SJS.
The long-term safety and effectiveness of modafinil have not been determined.
Modafinil may have an adverse effect on hormonal contraceptives for up to a month after discontinuation.
Addiction and dependence
The addiction and dependence liabilities of modafinil are relatively low. It shares biochemical mechanisms with addictive stimulant drugs, and some studies have reported it to have similar mood-elevating properties, although to a lesser degree.
Monkeys will self-administer modafinil if they have previously been trained to self-administer cocaine. As such, modafinil is classified by the United States FDA as a schedule IV-controlled substance, a category for drugs with valid medical uses and low but significant addiction potential.
Large-scale clinical studies have found no evidence of tolerance with modafinil at therapeutic dosages even with prolonged use (for 40 weeks and as long as three years).
Modafinil-associated psychiatric reactions have occurred in those with and without a pre-existing psychiatric history.