For patients who suffer from mood problems such as depression, the search for relief can be quite frustrating and time-consuming.
In addition to on-label uses, doctors are sometimes able to prescribe drugs approved by the U.S. Food and Drug Administration (FDA) for off-label purposes. One such instance is the use of Modafinil to treat certain types of mood disorders.
The use of modafinil for depression has been shown to reduce the severity of symptoms when taken with other prescription anti-depressants. Studies have shown that it may be an effective adjunct treatment for major depression and bipolar disorder.



- Stimulates wakefulness in the brain
- Promotes mental acuity & processing
- Enhances focus, motivation & energy
Overview of Modafinil
Related Topics
- What is Modafinil? (Provigil)
- How Does Provigil Work?
- Effects and Benefits
- User Reviews
- Typical Experiences
- Recommended Dosages
- How to Take
- Provigil Uses
- Use for ADHD
- Effects on Weight Loss
- Negative Side Effects
- Abuse Warnings & Dangers
- Comparison to Adrafinil
- Comparison to Armodafinil
- Comparison to Adderall
- Where to Buy
- Generic Modafinil Brands
- Is Modafinil Legal?
- How to Get Modafinil
- Review of Online Sources
Modafinil originated in France. It was first developed in 1976 at Lafon Laboratories by Michel Jouvet, a neurophysiologist and experimental medicine professor. The discovery of Modafinil occurred because of the previous discovery of Adrafinil.
Adrafinil is one of a group of benzhydryl sulfinyl compounds that was discovered in 1974. Adrafinil and Modafinil are very similar in molecular structure, with the only difference being that Adrafinil has a hydoxyl group on its terminal end that Modafinil lacks.
In research studies trying to determine Adrafinil’s mechanism of action, it was found that Adrafinil is metabolized in the body into the active Modafinil and the inactive modafinilic acid. This makes Adrafinil the pro-drug of Modafinil, and it is sometimes used in its place as a non-prescription alternative by people who want to use Modafinil for non-prescription nootropic related uses.
Modafinil is classified as a eugeroic, or wakefulness-promoting drug. The first clinical human studies were done using Modafinil for the sleep disorder narcolepsy.
Narcolepsy is neurological disorder that affects sleep and wakefulness. People with the disorder have problems maintaining wakefulness and experience excessive daytime sleepiness. In many different double-blind placebo-controlled studies done since the 1970s, it has been seen that compared to placebo, Modafinil significantly increases wakefulness and decreases excessive sleepiness in people with narcolepsy.
Modafinil has even been used as a model medication that other medications for narcolepsy are tested against. Studies have compared Modafinil and sodium oxybate to each other as well as against a placebo. It has been seen that both active medications improve sleepiness compared to placebo, and that there may even be an additive effect if they are used together.
Since it was first tested for improving wakefulness in people with narcolepsy, Modafinil has been tested for similar purposes in people with shift-work sleep disorder and obstructive sleep apnea/hypopnea syndrome. Both conditions have excessive sleepiness as a symptom. In research studies on the individual conditions, Modafinil has been seen to improve wakefulness and decrease excessive sleepiness compared to a placebo, as has been seen in narcolepsy trials previously.
In the U.S.A., the FDA has classified Modafinil as a Schedule IV prescription-only drug. Its approved uses are for narcolepsy, shift-work sleep disorder, and as an adjunct treatment for symptoms of obstructive sleep apnea/hypopnea syndrome.
Patients in the U.S.A. with a prescription can buy the medication in pill form as Modafinil, the generic form, or as Provigil, the brand name version available from Cephalon (the company that bought out Lafon Laboratories).
There has been much research in to using Modafinil for purposes other than decreasing excessive sleepiness associated with certain sleep disorders. Experts frequently refer to Modafinil as a so-called “smart drug,” a cognitive booster that can improve a person’s memory, focus, and attention span. Modafinil is frequently used without a prescription as a study drug.
It is sometimes prescribed off-label for attention-deficit hyperactivity disorder (ADHD). There have been many studies done that show that compared to a placebo, Modafinil significantly improves scores on various tests including the DSM IV ADHD Behavior Checklist.
Doctors are also able to prescribe modafinil for depression and other mood disorders, despite the fact that the drug has not been specifically approved for that purpose.
Modafinil for Depression
While modafinil and Provigil are not conventional medications to treat depression, they can create effects thought to help a patient with mood disorders. They appear to be particularly promising for individuals who suffer from major depressive disorder and bipolar disorder.
One double-blind study involving subjects with bipolar disorder suggested that a significant number of patients on Provigil experienced benefits in mood.
However, since modafinil stimulates the central nervous system, it also has the potential to actually raise levels of anxiety, a disorder that often co-exists with depression. Therefore use needs to be closely monitored by doctors.
Modafinil is one of the most recent avenues used to treat bipolar disorders. Researchers report that doses of 100 to 200 mg a day have alleviated bipolar symptoms after a six-week treatment cycle and when compared to patients who instead took a placebo. In the modafinil subjects, some improvement occurred by the end of the second week.
One traditional way of treating mood disorders is to use stimulants in addition to standard antidepressant drugs. Stimulants like amphetamines and methylphenidate form a kind of support system for traditional drugs.
Modafinil has stimulant-like effects, but it is not an amphetamine stimulant, and as a result, its use avoids some of the unpleasant side effects commonly associated with taking amphetamines, such as fast, irregular, pounding, or racing heartbeat, and a jittery shakiness in the arms and legs.

- Increases energy, wakefulness and motivation
- Boosts mental performance and focus
- Supports memory and cognition
Benefits of Modafinil for Mood Disorders
Recent work at a California university suggested that Provigil could be helpful to mood disorder patients because its use promotes a sense of well-being, boosts concentration, and cuts fatigue. Unlike many drugs that stimulate the central nervous system, it has shown little potential to be habit forming.
These factors suggest that it could be a better choice than a traditional stimulant to treat anhedonia, which is the lack of ability to feel pleasure from things normally considered enjoyable.
A small New Jersey study that followed seven patients – four with major depression and three with bipolar symptoms – used modafinil after these patients either failed to respond to a conventional antidepressant or responded only partially.
By the end of two weeks, all the patients reached full or partial remission. The fatigue that these patients experienced prior to taking Modafinil significantly responded to the drug. No significant side-effects were observed that would lead to discontinuing the drug.
Experts have noted that around a third of individuals diagnosed with depression get little if any benefit from using only antidepressants as medication, even when undergoing psychological counseling.
A 2013 study that involved three U.K. universities suggested that taking modafinil along with conventional antidepressants treated depression more effectively than using only antidepressants.
The same study reviewed the records of 568 patients diagnosed with unipolar depression and 342 considered to suffer from bipolar depression.
It was concluded that the use of modafinil both cut the level of depression and improved remission rates. Additionally, the drug was found to positively affected levels of fatigue and sleepiness.
Modafinil and Dopamine
Researchers believe that the key to modafinil’s effectiveness in treating mood disorders is linked to the role of dopamine in the brain. Brain cells called neurons utilize chemical messenger molecules known as neurotransmitters in order to communicate.
Many healthcare professionals link mental illness and mood disorders like depression at least in part to the dysfunction in at least one neurotransmitter system.
Dopamine, made from a modification of the amino acid tyrosine, is a neurotransmitter. It regulates motor activity and is also responsible for motivation, reward, pleasurable feelings, and attention.
Loss of interest in pleasurable activities, feelings of sadness, sleep pattern changes, and alteration of appetite level are all associated with depression.
Without adequate levels of dopamine, effective communication with neurons is impossible. Drugs traditionally used to treat depression typically target the group of neurotransmitters called monoamines. They include dopamine.
In one study of modafinil and dopamine, 10 male subjects were divided into two groups. One group took Provigil, while the other took a placebo.
Data from the Provigil group showed that the drug blocked dopamine transporters. These transporters remove dopamine from brain synapses. Blocking these transporters in the brain acutely increased dopamine levels.
For professionals who treat mood disorders, modafinil for depression treatment offers future potential to become a medication of choice, especially for patients with limited or no response to traditional drugs.
Modafinil’s lack of several side effects associated with commonly used stimulants to treat these conditions could offer additional patient benefits.
Modafinil Side Effects
Some doctors will prescribe Modafinil instead of traditional amphetamine stimulants to avoid associated side effects. This is often a successful plan, because there are fewer side effects associated with Modafinil use. However there are still some side effects to be aware of. The most common side effects are headaches, nausea, anxiety, nervousness, back pain, diarrhea, and decrease in appetite.
There are some rare but serious side effects that have been seen in people who take Modafinil. In research there have been no reported adults cases, but one reported pediatric case of Stevens-Johnson syndrome, a rare skin and mucous membrane condition that causes fever and flu-like symptoms and a blistering rash. Other skin reaction conditions that have been seen very rarely include toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS).
Often side effects occur due to too high of a dosage. Everyone’s personal physiology is different, and it is possible that some people need a lower dosage to not experience side effects. Speak with your doctor to determine the best dosage for your needs. If you have any serious side effects, stop taking Modafinil and seek medical attention immediately.
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Article last updated on: May 12th, 2018 by Nootriment