Modafinil and Depression

Modafinil and Depression

Can you use Modafinil for treating depression? Does Provigil Cause Depressive Condition? All answers read on this article.

Definition of Depression

Depression, professionally known as major depressive disorder or clinical depression, is a serious mood disorder characterized by mild to severe symptoms including depressed mood, loss of appetite and pleasure in once enjoyed activities, increased fatigue, feelings of worthlessness, guilt, and shame, difficulty concentrating, and thoughts of death or suicide.

For a diagnosis of clinical depression or major depressive disorder, these symptoms must persist for two weeks or more.

One in six people will experience depression at some point in their life, with women being more likely to suffer from the disorder. Depression, contrary to popular belief, is not just having sad feelings. Along with changes in mood, the disorder can manifest physical issues such as fatigue, lack of focus and concentration, and sleep issues like insomnia or hypersomnia (excessive daytime sleepiness).

There are different kinds of depression that have slightly different symptoms or that develop under a set of unique circumstances. Persistent depressive disorder or dysthymia is a type of depression that can last two years or more.

Modafinil and Depression

Perinatal depression is a mood disorder that occurs after a woman gives birth and usually clears within two weeks of delivery. Psychotic depression is depression that is characterized by episodes of psychosis, and Seasonal Affective Disorder is depression that occurs during the winter months when exposure to sunlight is diminished.

Major Symptoms of Depression


There are many symptoms associated with depression, although each individual might not necessarily experience all of them.

A person suffering from depression may suffer from persistent sadness, anxiety, irritability, feelings of hopelessness, loss of interest in hobbies and activities, feeling restless, appetite and/or weight changes, thoughts of death and suicide, aches and pains, headaches, cramps, and digestive problems without another physical cause, decreased energy and fatigue, and difficulty concentrating and making decisions. The last two symptoms are ones that are specifically addressed with the drug Provigil (Modafinil).

What Is Modafinil?

Provigil or Modafinil is an eugeroic drug, a substance that promotes wakefulness. The drug is also considered a nootropic, a substance that improves cognitive functions like executive memory, creativity, and motivation. It’s often referred to casually as a “smart drug” because of its cognitive enhancing abilities. Provigil was approved by the FDA in 1998 to treat excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work sleep disorder. Although Modafinil has never obtained FDA approval for the treatment of depression, anecdotal reports suggest the drug is highly effective as an off-label treatment for the disorder.

Can I Use Provigil (Modafinil) for Depression?


Modafinil isn’t FDA approved for depression but it can be used as an off-label treatment for depressive disorders. The drug is considered relatively safe with a low potential for abuse, but some psychiatrists and doctors might not prescribe it for depression. There are certain scenarios, however, where Modafinil could be effective.


Apathy can be a dominant characteristic of depression and studies have shown that Provigil can significantly reduce this symptom. One study revealed a patient with bipolar disorder saw a drop in her “apathy” rating from 61 to 31 following 16 weeks of treatment.

Atypical Depression

Atypical depression is a subtype of major depressive disorder characterized by increased appetite, weight gain, excessive sleepiness, and marked fatigue. There is evidence that Provigil helps atypical depression by addressing the hypersomnia portion of the disorder and possibly enhance weight loss due to its ability to boost dopamine levels and increase overall energy.

Comorbid Narcolepsy

Since Provigil was approved as a first-line option for use in treating narcolepsy, patients that have depression with comorbid narcolepsy, obstructive sleep apnea, or shift work sleep disorder could be considered good candidates for the drug.

Treatment-Resistant Depression


Refractory forms of depression, or depression that does not respond well to traditional treatments, may also benefit from Provigil. The drug is generally regarded as being safer than most antidepressants with fewer side effects and withdrawal symptoms. The unique mechanism action of Provigil could be very effective in treating those individuals who are resistant to first-line depression medications.

How Provigil Treats Depression

Although the mechanism of action through which Provigil promotes wakefulness is unknown, it is believed to help excessive daytime sleepiness through minor dopamine reuptake inhibition (DRI), increasing histamine in the hypothalamus, and stimulating orexin receptors. It can also slightly increase levels of norepinephrine and serotonin in some regions of the brain. Furthermore, the drug has a unique mechanism that can enhance electronic coupling thereby increasing gamma brain waves which are responsible for perception of reality and the processing of information. In layman’s terms, the medication can promote wakefulness and lift brain fog, i.e. slow psychomotor activity. Modafinil has also been found to have a stabilizing effect on mood.

Two of the primary symptoms of major depression are excessive fatigue and brain fog. Starting in 2000, researchers began to study the effects of Provigil on depression, even though it was not approved for that disorder. Since individuals with depression often complain of chronic fatigue, low energy, and excessive daytime sleepiness, researchers believed that the stimulatory action of Provigil might be an effective treatment for bipolar depression, major depressive disorder, seasonal affective disorder, and atypical depression.

What Modafinil Dosages Are the Best for Depression?


The majority of people taking Modafinil take the drug in the morning or before they start their shift at work. A single dosage of the drug can help alleviate fatigue and give individuals clarity and focus. The medication comes in two doses, 100 mg and 200 mg. The average recommended dose for Modafinil is 200 mg once a day, although individuals may start on a lower dose, say 25 mg, to find which dosage works best for them. Quantities above 200 mg add no beneficial effects.

Time of day for dosage can vary from person to person but individuals note that the drug can take up to three hours to really kick in, so most patients will take Modafinil in the morning upon waking. Modafinil can be taken with food or on an empty stomach. Individuals report that headaches occur when they’ve taken too much of the drug.

Studies Done on Provigil

In 2000, research was done on seven patients with bipolar depression and major depressive disorder who were not responding to first-line antidepressant treatments. They were given Provigil as an adjunct treatment to their antidepressant in 100 mg and 200 mg doses. All seven patients experienced partial or full remission of their disorder within the first two weeks with minimal side effects.

Provigil 100 mg

Another study in 2004 analyzed the drug in patients with seasonal affective disorder (SAD) or seasonal depression. Individuals who experience this disorder often complain of excessive sleepiness or hypersomnia during seasonal changes, particularly in the winter months. This is usually caused by lack of exposure to sunlight. In this study, 12 patients were given Provigil starting at 100 mg doses which were then increased to 200 mg. In nine of the patients, the drug significantly improved symptoms within one week of treatment and maintained its efficacy through the eight weeks of the trial.

Other studies have been done since then on the efficacy of Provigil in the treatment of depression. In all of the studies, a significant percentage of individuals taking the drug experienced improvement in their depression. Through reviews of these studies, researchers concluded that Provigil’s unique mechanism of action elicited a variety of neural changes that led to its antidepressant effects and it, therefore, was highly effective as an adjunct treatment for depressive disorders.

Why This Drug May Help to Beat Depression?

Provigil was found to be successful in improving cognitive function. The drug is a well-known nootropic, a substance that enhances cognition. Individuals with depression often complain of brain fog or cognitive impairment. It is thought that Provigil works to alleviate this symptom by improving deficiencies in neurotransmitters, correcting abnormal brain wave activity and/or insufficient regional activation. Since improved mental performance can lead to greater confidence in social and work situations, the action of the drug can significantly improve depression.


Another major symptom of depression is feeling under-stimulated. Reduction in central nervous system stimulation can result in a depressed mood and low energy. Provigil works to increase CNS stimulation resulting in improved energy and psychomotor activity. The drug also minimally affects certain neurotransmitters like norepinephrine, dopamine, and serotonin. Deficiencies in dopamine and serotonin are thought to be factors in major depression, so Provigil’s boosting action of these could lead to improvements in the disorder.

The effects of Provigil (Modafinil) against fatigue compared to other stimulants is outlined in the following table:

Restoring Alertness Duration of Action Subjectively reported adverse effects Recovery Sleep adverse effects
Modafinil Effective 2 3 No
Amphetamine Effective 1 2 Yes
Caffeine Effective 3 1 No

A wealth of evidence obtained from clinical trials suggests that Provigil is effective in the treatment of depression. Unlike traditional antidepressants that can take six to eight weeks on average to work, Provigil can produce improvements in cognitive function, motivation, productivity, and energy levels on the very first day. And since the drug’s side effect profile is minimal, many individuals may prefer the drug over existing antidepressants.

Can Modafinil Cause Depression?

While most individuals taking Modafinil report a decrease in depression from the drug, some users have reported that their depression actually increased with use. Although evidence for this is purely anecdotal, some patients have noted that while the drug helped their fatigue, it actually made other symptoms of the disorder, like depressed mood, even worse. Although Modafinil has limited side effects, in certain people it could exacerbate depression.

The drug has been known to increase anxiety, another symptom of major depression, which can lead to a decrease in mood and cognitive function. The long-term effects of Modafinil are relatively unknown. Preliminary evidence suggests that it is safe, but individuals who suffer from anxiety may want to avoid the drug.

Side Effects of Modafinil

Modafinil is thought to be generally safe with limited side effects. Talk to your doctor if you experience any of the following:

Side Effects of Modafinil

  • fast/pounding/irregular heartbeat;
  • fever;
  • nausea;
  • depression;
  • nervousness;
  • diarrhea;
  • dry mouth;
  • upper respiratory tract infection;
  • dizziness;
  • trouble sleeping (insomnia);
  • anxiety;
  • easy bruising or bleeding;
  • chest pain;
  • hallucinations;
  • agitation;
  • headache;
  • mental/mood changes (such as confusion, depression, hallucinations, rare thoughts of suicide).

Where to Buy Modafinil Pills?

Modafinil is a prescription drug that can be purchased from online pharmacy depending on what country the patient is in. There are different versions of the drug by different manufacturers but online purchases are thought to be cheaper than buying the medication in a brick and mortar pharmacy. All online Modafinil is sourced in India but can be purchased through online vendors. Although products offered by e-commerce sites are essentially the same, customers should check to make sure a vendor is reliable before purchasing