Table of Contents
Modafinil is a eugeroic medication, which means it is wakefulness-promoting agent.
It is a central nervous system (CNS) stimulant medication used primarily to help people remain awake, combat fatigue, and increase concentration. As a stimulant, it is not as powerful as amphetamine, but it does produce similar effects to the more potent stimulants, only at a less intense level of CNS arousal.
Modafinil is used clinically to treat conditions such as sleep disorders like narcolepsy, to assist people who suffer from sleep apnea and as a result experience excessive daytime sleepiness, and for people with shift work disorder who suffer from excessive sleepiness due to having a work schedule that is out of sync with their daily sleep/wake routine.
Modafinil also has off-label uses as a cognitive enhancer, to help people to focus their attention more efficiently, and it has been used to treat excessive fatigue associated with medical conditions like multiple sclerosis, cancer, or Parkinson’s disease. There is also evidence that modafinil may be useful in as an assistive medication added to antidepressant medications in the treatment of severe depression.
As one might expect, the drug has also been used as an off-label medication to assist in the treatment of ADHD. There has been some interest for its potential uses in the military, for airline pilots, and even for astronauts due it its ability to promote wakefulness and to increase concentration.
Brief History of ModafinilAccording to Michael Billard, MD, co-author of the book, Sleep Medicine: A Comprehensive Guide to Its Development, Clinical Milestones, and Advances in Treatment, modafinil was originally developed in the 1970s in France where early research was performed, and the drug was found to be an effective treatment for narcolepsy. The final clinical research was completed in 1986 indicting that the drug was not only effective for treating narcolepsy and other sleep disorders, but also reduced the need for sleep in healthy people. The drug received FDA approval in 1998 and was marketed under the brand name Provigil in the United States.
Modafinil is sold under a host of different brand names. For example, in the United States, the UK, Hong Kong, and several other countries, it is sold under the brand name Provigil. In France and Japan, it is marketed under the name Modiodal, and in Switzerland, it is sold under the brand name Modasomil. The drug is manufactured by Cephalon, Inc., and there is an FDA-approved generic version.
Mechanism of Action
According to Dr. Billard, the exact mechanism by which modafinil works is unknown at this time; however, it is believed that the drug stimulates the production of a class of neurotransmitters called monoamines that include the neurotransmitters:
One of the functions of these neurotransmitters is to stimulate the hypothalamus in the brain, which produces hormones that control the sleep-wake cycle.
It is suggested that this may be the main action of modafinil that contributes to its clinical effects. Eugeroic type medications also include similar drugs like adrafinil (Olmifon, which is now discontinued) and armodafinil (Nuvigil).
Recommended Treatment with Modafinil
Modafinil is taken in tablet form, and the tablets are available in 100 mg and 200 mg doses. The recommended dosage for treatment in people with narcolepsy or patients with excessive sleepiness due to obstructive sleep apnea is 200 mg once a day, typically taken in the morning. The same dosage is recommended for people with shift work disorder, except that it is recommended that the medication be taken one hour before work.
The half-life of modafinil is about 15 hours, so only one dose is needed for these conditions. Nonetheless, larger doses of up to 400 mg per day taken as a single dose have been reported to work well in people, but there appears to be no empirical evidence for additional benefits beyond the standard dosing.
Side-Effect Profile of Modafinil
Some sources also advise close supervision by a physician when using modafinil.
Some also advise against using modafinil for geriatric patients, pediatric patients, patients with liver problems, patients with heart problems, or patients with psychotic disorders.</p>
- High blood pressure
- Loss of appetite
- Dry mouth
The most updated information on the effects of modafinil overdose has indicated that, in clinical trials, adverse reactions that were reported at very high doses of modafinil include the following symptoms:
- Excitation, anxiety, or agitation
- Slight or moderate elevations in hemodynamic parameters (e.g., blood pressure or heart rate changes such as heart palpitations)
- Psychosis in rare cases
There do appear to be some reports of death resulting from modafinil overdose when taken in combination with other drugs; however, most sources indicate that there are no valid reports of death occurring by an overdose of modafinil taken alone.
Modafinil is classified as a Schedule IV controlled substance, meaning that it cannot be legally obtained without a prescription from a physician. According to the United States Drug Enforcement Agency, the drugs classified in this category are believed to have a very low potential for abuse or physical dependence (addiction). Nonetheless, there does appear to be some research to suggest that modafinil might have a potential for addiction or abuse:
- A 2009 neuroimaging study presented in the Journal of the American Medical Association reported that modafinil blocked the reuptake of the neurotransmitter dopamine in neurons in an area of the brain known as the nucleus accumbens. The nucleus accumbens is often wrongly referred to as the “pleasure system/center of the brain” or other similar label; however, it is an important area in the experience of being rewarded that is associated with repeating a particular behavior. This observed action of modafinil is similar to the action of very addictive drugs, such as cocaine, and the researchers suggested that modafinil may have an addictive potential in people who are vulnerable for drug dependence.
- Research has indicated that there is low-level tolerance developed with modafinil use, but the research is mixed regarding withdrawal effects associated with its discontinuation. If there are any physical withdrawal effects associated with modafinil, they are most likely mild; however, the development of even mild tolerance suggests that some people may abuse the drug in order get the same affect that once occurred at lower doses, and this might lead to psychological feelings of dependence. There is a case report where this very issue occurred in an individual who used very high doses of modafinil for daytime sleepiness. Nonetheless, true physical dependence from modafinil use or abuse is most likely very rare.
- As discussed below, modafinil use is becoming popular with students due to its concentration-enhancing abilities. This type of use may lead to more reports of people who take modafinil being diagnosed with substance use disorders as a result of very chronic modafinil use.
Because most of the research indicates it has a low potential for addiction, modafinil has been suggested as being potentially useful in treating people recovering from addiction to cocaine or other drugs, such as methamphetamine, much in the same way methadone is often considered to be useful in recovery from addiction to opiates. One recent double-blind placebo-controlled study found no overall effects of treatment with modafinil compared to a placebo for cocaine addiction, but it did find significant differences in the reduction of self-reported cocaine cravings in people addicted to cocaine and higher maximum consecutive days of no cocaine use in the modafinil treatment group compared to the placebo group.
Another recent study found no significant effect for modafinil compared to a placebo for treating methamphetamine addiction, but the researchers suggested that further research needed to be completed. This particular study had a few methodological weaknesses, including small sample sizes, limited dosages used in the study, and the limited duration of the study.
Modafinil as a Cognitive Enhancer
Modafinil has received some publicity as a potential smart drug in the never-ending quest to find drugs that increase a person’s mental abilities. As a result of this claim, college and high school students, working professionals, and others have used it in attempt to increase their brainpower. However, the ability of modafinil to assist one’s cognitive functioning or its use as a cognitive enhancer is very simply understood by its mechanism of action, and there is no mystery or special quality associated with it.
Because modafinil is a stimulant at low to moderate doses, it will increase the ability of many people to concentrate in the same way that having a few cups of coffee increases concentration in individuals. There is no magic to this effect. Most stimulant drugs can increase concentration at low levels, but at higher levels, they can actually make one even more distractible.
Modafinil does have some useful clinical applications; however, it is not a wonder drug.