Modafinil for Depression: An alternative treatment that works

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Modafinil for Depression: An alternative treatment that works

Modafinil: An alternative treatment for depression


Modafinil is a potent wakefulness-enhancing agent that has been in use since the ’90s as a treatment for various sleep disorders.

There is no such thing as a one-size-fits-all approach when it comes to treating depression.

Recent years have seen a rise in off-label use of Modafinil, and depression is one of the top reasons.


But does Modafinil work as an antidepressant or is it merely a “placebo claim” of unsupervised users?


This article will help you understand the link between Modafinil and depression, as well as the science behind each…



What is depression?


Depression is a common mental illness that is defined by feelings of sadness, anger, hopelessness and other negative feelings.


It’s quite common, as the Center for Disease Control and Prevention (CDC) has shown.

The CDC has estimated that 8.1% of American adults aged 20 and over have suffered from depression between 2013 and 2016.


The severity of depression varies from individual to individual.


Most people experience one or more of the following symptoms:


  • Bad mood (“feeling low”)
  • Lack of energy (“feeling sluggish”)
  • Insomnia or sleeping too much
  • Weight loss or weight gain which isn’t related to diet
  • Feelings of worthlessness and hopelessness
  • Loss of interest in pleasurable activities
  • Lack of motivation and bad decision-making
  • Difficulty focusing and concentrating
  • Suicidal thoughts


Depression is often confused with periods of sadness or “bad days”, which are normal for any human being.

Symptoms should persist at least 2 weeks before being diagnosed as depression.

Also, other conditions such as vitamin deficiency, thyroid issues or brain tumor may cause similar symptoms.


Depression can occur at any age, though it’s most common during late teens and mid-twenties.


Women experience depression more than men, with some studies estimating that 1/3 of all women experience at least one depressive episode during their lifetime.


Risk factors of depression


Depression can affect anyone, regardless of their age, sex, health or social status.

Contrary to popular belief, even those who are wealthy and/or successful can go through depression.

Depression isn’t fully understood by scientists, yet those who have studied it extensively have found several factors that cause it:



  • Genetics. One may be predisposed to go through a depressive episode if another family member is known to have suffered from depression.


  • Biochemistry. Chemical imbalances related to neurotransmitter levels in the brain may be the root cause of depression.


  • Personality. People who are pessimistic by nature or those who tend to worry a lot have a higher likelihood of developing depression during their lifetime.


  • Society or external factors. Exposure to violence, abuse, crime or other negative influences will make one more vulnerable to depression.



Treatment for depression


Depression is one of the easiest-to-treat mental health disorders. Between 80 to 90 percent of the people who undergo treatment eventually manage to recover from depression. Every patient undergoing treatment manages to get at least some relief.

There are several methods to treat depression, all of which may be combined with each other for increased effectiveness:


Medication. A chemical imbalance in the brain is a common cause of depression. In this case, medication is prescribed to the patient as a means to modify one’s brain chemistry over a period of time.

Anti-depressants are usually given to help one cope with the debilitating side of depression.

Alternative medications, such as tianeptine sulfate or Modafinil, that don’t fall in the anti-depressant category have been studied and proven to help people recover even from severe forms of depression.


Psychotherapy. Therapy sessions are sometimes enough to help the sufferer recover from mild forms of depression. In the case of moderate and severe types of depression, psychotherapy is accompanied by medication as well.

Cognitive behavior treatment (CBT) is a method in which the focus is on problem-solving and helping the patient confront himself and destroy the barriers of distorted thinking.

Psychotherapy may be practiced in groups or during one-on-one sessions.


Exercise. The rapid evolution from hunter-gatherer to office monkey can definitely contribute to the likelihood of depression occurring.

It’s against our nature as human beings to be sedentary, and lack of exercise may be a serious contributing factor to depression.

Exercising at least 30 minutes/day for 5 days/week will increase endorphin levels, which will help the person better deal with depression.


Alternative remedies. Acupuncture and meditation can help you purify your soul, and are definitely worth considering.

Herbal supplements such as St. John’s Wort, Valerian root or Ginseng are believed to possess anti-depressant qualities.

Still, a talk with a physician is required, as some may interact negatively with other medication.



How does Modafinil work?


Modafinil’s mechanism of action is more complex than typical stimulants and isn’t fully understood by the scientific community. Rather than affecting one or two neurotransmitters in a strong way, Modafinil affects several ones in a more subtle manner.


Modafinil increases serotonin in the amygdala, prefrontal cortex and the dorsal raphe. [R][R]

In some cases, Modafinil produces synergistic effects when combined with SSRIs (selective serotonin reuptake inhibitors). [R]

Still, in spite of many studies conducted on animals, one human study in which Modafinil and another SSRI were given for fatigue and sleepiness failed to show synergistic anti-depressive effects. [R]

Modulation of this neurotransmitter causes the user to have a better mood and feel more energized.


Modafinil increases norepinephrine, a key neurotransmitter in the brain that is responsible for the “fight-or-flight” response. [R]

Increased levels of norepinephrine cause the user to feel more aware and alert.

Other stimulants such as caffeine also increase norepinephrine, which explains the increased risk of anxiety when mixing Modafinil with stimulants.


Modafinil increases dopamine by blocking the dopamine transporter (DAT), thus acting as a dopamine reuptake inhibitor.

Even though the action on dopamine receptors is similar to that of cocaine, Modafinil is considerably more gentle, hence the non-existent crash after the effects have worn off. [R][R]


Modafinil increases histamine through its action on orexin-releasing neurons.

Orexin increases arousal and wakefulness and histamine also promotes wakefulness.

Histamine regulates the sleep-wake cycle and both neurotransmitters produce stimulatory effects. [R][R][R]


Modafinil increases glutamate and decreases GABA. The first is the main excitatory neurotransmitter that also influences the levels of dopamine, norepinephrine, serotonin and orexin.

GABA is the main inhibitory neurotransmitter that is responsible for decreasing brain activity and helping one “shut down” at the end of the day.

Modafinil’s action on the two neurotransmitters isn’t fully understood, as studies have shown that it differs from one region of the brain to the other. [R]



Is Modafinil a viable choice for treating depression?


Modafinil’s relative safety and low addictive potential have contributed to its popularity, with many people even substituting it for Adderall, Ritalin or anti-depressants.


Most anti-depressants focus on modulating serotonin receptors. Modafinil’s effectiveness as an anti-depressant stems from its action on dopamine.


Dopamine is the neurotransmitter that is responsible for the “reward system” in the brain. Also, it plays a key role in many other functions such as homeostasis, memory formation, libido, mood regulation and heartbeat control. All these functions are affected more or less when experiencing major depressive episodes.


To put it in simple terms, Modafinil can do something extra than your typical mind-numbing anti-depressant.


Modafinil can provide the necessary dopamine boost to help the sufferer climb out of the “dark hole”.


The “dark hole” is a metaphor used by people to describe what depression feels like. The dopamine boost may be just the thing needed to help the user “see the light” and “climb out of the hole”.


Still, other neurotransmitters are believed to influence the anti-depressant effects of Modafinil.

One study has shown that Modafinil’s efficacy as an anti-depressant may stem from its action on histamine and noradrenaline receptors.

Also, increased glutamate and serotonin levels are also believed to play a role when it comes to treating depression. [R]


One study directly investigated the effectiveness of Modafinil as an antidepressant. It has shown that 67% of those who were taking Modafinil had seen improvements in symptoms. [R]



Where can you get Modafinil?


The main issue is that Modafinil hasn’t yet been approved for the treatment of depression, making it difficult for doctors to prescribe it as Provigil or Alertec.

This has led many people to order Modafinil and Armodafinil from the Internet.

Two of the most popular brands that are also FDA-regulated are Waklert and Modalert.

You can buy them from, an American-run Modafinil pharmacy that offers competitive pricing and fast shipping.


Before deciding to do so, take a moment to understand if Modafinil is indeed the right choice for you or the person who’s experiencing depression…



Understanding the link between Modafinil and depression


Modafinil’s mechanism of action triggers several responses that affect the user both physically and mentally in a subtle, yet noticeable manner.


Modafinil helps manage the effects of depression, though, in some instances, it can also help regarding the causes of its occurrence.


If you’re suffering from depression, Modafinil may benefit you in the following ways:



Modafinil for weight loss


People who are depressed may gain or lose weight without any serious changes in diet.


On the other hand, overweight people are more prone to depressive episodes due to low self-esteem and chemical imbalances in the brain.


The CDC (Center for Disease Control) estimates that around 43% of those who are diagnosed with depression are also obese. The CDC has also claimed that adults who’ve been diagnosed with depression are more likely to be overweight. [R]


Modafinil suppresses appetite. Some view this as a typical stimulant-like side effect of Modafinil. For others, it can be incredibly effective to control overeating during depressive episodes.


Another way in which Modafinil helps in weight loss is through its positive effects on motivation. The dopamine boost may give one the necessary willpower to form healthy habits such as exercising, sports, hiking, biking, etc.



Modafinil for lack of motivation


A depressed individual may go through several negative feelings that may severely hinder quality of life.


Call it a vicious circle that makes it more difficult to make the necessary changes to get out of a depressed state.


Modafinil’s subtle influence on dopamine receptors provides the sufferer with the necessary boost to help him or her get back on track with normal life.



Modafinil for difficulty in concentration


Depression can be difficult to manage when you also have a job that you need in order to pay the bills.


Inability to concentrate, brain fog and sluggishness further adds stress to an already unbalanced mind.


Modafinil is widely used by healthy individuals who want to boost their productivity at work. It can also be beneficial to depressed people who want to face their depression with productive activities.


Also, depressed people who are on anti-depressants typically experience sedation, thought deceleration and drowsiness when taking Xanax, Valium or other substances like these. Modafinil will cancel out their effects.



Should you be using Modafinil for the treatment of depression?


First of all, if you intend on using Modafinil as a treatment for depression, you should consult your physician.

The doctor can prescribe Modafinil to you, or he can give you the go-ahead to buy Modafinil from online pharmacies.

Modafinil may be beneficial for those suffering from depression, but it should also be avoided in these conditions:


  • If the sufferer has other weight-related conditions such as anemia or anorexia
  • If the depression is severe
  • If the depressed person is suffering from severe anxiety
  • If the sufferer has underlying heart problems


Modafinil can help mitigate the symptoms generated by depression and it may also help treat the underlying cause.

Don’t be afraid to bring this up with your doctor, as there are sufficient studies that can back up Modafinil’s effectiveness when it comes to depression.

The doctor may not be able to prescribe Modafinil, but you can always procure it online.

Just remember to stick with the most popular brands (Modalert, Waklert, Modvigil or Artvigil) and to be on the lookout for scammy online vendors.



References | Products – Data Briefs – Number 303 – February 2018 | Differential enhancement of dialysate serotonin levels in distinct brain regions of the awake rat by modafinil: possible relevance for wakefulness … – PubMed – NCBI | Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: a dual probe micro… – PubMed – NCBI | Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatig… – PubMed – NCBI | Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. – PubMed – NCBI | Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. – PubMed – NCBI | Electrophysiological and amperometric evidence that modafinil blocks the dopamine uptake transporter to induce behavioral activation. – PubMed – NCBI | Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. – PubMed – NCBI | The effect of orexin-A and -B on the histamine release in the anterior hypothalamus in rats – ScienceDirect | Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. – PubMed – NCBI | Effects of the vigilance promoting drug modafinil on the synthesis of GABA and glutamate in slices of rat hypothalamus. – PubMed – NCBI | Antidepressant treatment with low dose modafinil | A retrospective chart review of the effects of modafinil on depression as monotherapy and as adjunctive therapy. – PubMed – NCBI | Products – Data Briefs – Number 167 – October 2014


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