In recent years, modafinil has become EXTREMELY popular.
It is now the most frequently used central nervous system stimulant.
Modafinil was developed in the 1970s in France by neurophysiologist and emeritus professor Michel Jouvet and Lafon Laboratories (since acquired by Cephalon Inc).
The popular Smart Drug was first approved for narcolepsy treatment in France in 1994, and in the USA in 1998 as a treatment for sleep disorders due to shift work or obstructive sleep apnea.
Modafinil received approval from the FDA for use on narcolepsy grounds, but it is also prescribed off-label to treat conditions including:
- Chronic fatigue
- Fibromyalgia Syndrome
- Myotonic Muscular Dystrophy
- Parkinson's disease
- Multiple Sclerosis
... and daytime sleepiness caused by antidepressants.
Modafinil is available as an oral tablet or a solution for injection (which provides a way faster uptake into the bloodstream).
The dosage depends on the condition being treated and whether or not it is taken with other medications.
For example, a single tablet of Provigil (modafinil) 200mg costs about $11, whereas a month's supply of Armodafinil (Nuvigil) 150mg for sleep disorders costs around $500.
In this article, however, I will discuss the effectiveness of modafinil in treating depression and whether it could be used to replace antidepressant drugs.
So How Does Modafinil Actually Work?
Modafinil is an eugeroic, meaning that it promotes wakefulness like an amphetamine or a stimulant, but it acts in the brain differently than a typical stimulant.
It activates specific dopamine pathways in the brain specifically those containing D2 receptors that are responsible for arousal.
It also suppresses GABA-mediated pathways that are associated with sedation.
By this mechanism, modafinil precludes many of the side effects associated with most stimulants because it does not affect other hormones in the body (e.g., epinephrine).
It also inhibits histamine receptors, which causes it to be more tolerable than stimulants. Modafinil's mechanism of action is similar to that of methylphenidate, the pharmaceutical name for Ritalin.
Can Modafinil Treat Depression?
There is an irony in using a drug prescribed for narcolepsy - which can cause sleepiness - to treat depression.
But in fact, modafinil has shown positive results treating depression without causing fatigue or daytime drowsiness - a problem with traditional antidepressants.
A clinical study published in The Journal of Clinical Psychiatry showed that modafinil exhibited much better results than a placebo (i.e., dummy pill) in reducing co-morbid symptoms in depressed patients who exhibited excessive daytime sleepiness.
In another study published in Pharmacopsychiatry, researchers concluded that:
"Modafinil is an effective and well-tolerated adjunct treatment for depression."
In 2006, the FDA approved Provigil to treat narcolepsy and obstructive sleep apnea, but it is still under review as a potential use for treating depression.
Independent sources such as HealthCentral.com report that modafinil is an effective treatment for depression and some insomnia-related conditions.
From what I could find from the data available online some antidepressants may be less effective in treating depression than others, but modafinil seems to be one of those 'sure things' when it comes to treating this condition. That being said, I'm not a Doctor, so you'll have to do your own research.
It's also worth noting that there are limited studies on the use of modafinil for depression, but existing evidence suggests it may be useful in relieving some symptoms.
Modafinil reduces fatigue by promoting wakefulness, while other antidepressants tend to give a feeling of sleepiness or heaviness.
Modafinil has been shown to improve mood and cognitive function in people with anorexia nervosa (an eating disorder characterized by excessive thinness) and schizophrenia (a mental illness characterized by delusions and hallucinations).
Is Modafinil Considered An SSRI?
Many American psychiatrists and psychiatrists abroad are now prescribing this drug for many mental health issues where stimulants are being used for treatment, including anxiety disorders (e.g. panic attacks) and ADHD.
However, modafinil does not seem to be very effective in treating severe clinical depression.
As of 2021, it's only a handful of drugs that have been approved by the FDA for treating clinical depression in adults.
However, there has been interest in using modafinil for this purpose due to the narcolepsy-related success it has had with many patients suffering from this condition.
That being said, one of the most controversial topics regarding modafinil is whether or not it is an SSRI (selective serotonin reuptake inhibitor).
In other words, is it likely that modafinil works by blocking the reuptake of serotonin in order to prevent its removal from the brain?
If not, does this mean that modafinil cannot be used to treat depression?
Is it more likely to work via other mechanisms?
I think it's important to understand how this drug work at a molecular level before I discuss its effectiveness and safety in treating depression or anxiety disorders.
Modafinil is Structurally Similar to Serotonin
Although modafinil is not chemically similar to SSRIs like Prozac, it is structurally similar to serotonin (5-HT).
Modafinil binds itself to the serotonin transporters and blocks their reuptake.
This means that when you take modafinil, it sits on your brain's serotonin transporter and prevents your body from re-absorbing the stored-up serotonin in your synaptic clefts (the anatomical gaps between neurons in the brain).
SSRIs work by keeping an excess of serotonin in the synapses so that it can remain there longer.
The result of this is that it takes less time for any neurotransmitter, including serotonin, to be re-absorbed into our presynaptic neurons so that they can be utilized again.
This means SSRIs are more long-acting than modafinil and have a slower onset of action.
Modafinil Can Boost Serotonin Levels
Modafinil has been shown to increase serotonin levels in the brain.
It is important to understand that not all depression is caused by a deficiency of serotonin - but pre-clinical studies suggest that low serotonin levels in the brain may contribute to the development of depression.
It appears that modafinil works by increasing serotonin transporter sites, as well as boosting the number of secondary messengers (e.g., dopamine) in the brain.
Secondary messengers are substances that are released by one neuron and act on another neuron or on a group of neurons.
Although modafinil does not seem to work on regulating serotonin (5-HT) like SSRIs, it does boost its receptor sites.
As mentioned earlier, there is controversy over whether modafinil can be classified as an SSRI or not. It is seen as a "dual-action" drug, which means that it can act on the body in more than one way.
If you would like to learn more about modafinil and its effects on people with depression or bipolar disorder, there are some great resources over at Examine.com.
They offer a comprehensive overview of this issue by citing scientific studies both for and against modafinil being used to treat depression.
What Other Drugs Are Effective At Treating Depression?
At the moment, there are three types of drugs approved by the FDA to treat major depressive disorder (MDD; clinical depression).
- Selective serotonin reuptake inhibitors (SSRIs)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- and Monoamine oxidase inhibitors (MAOIs).
SSRIs are considered safer than MAOIs because they have lower rates of severe side effects when compared to other antidepressants.
However, SSRIs are not as effective at treating more severe symptoms such as suicidal ideation or self-harming behaviors.
SNRIs, like venlafaxine or duloxetine, are considered to be "a good choice for people who have not responded adequately to SSRIs but do not tolerate SSRIs or SNRIs."
They work particularly well in treating people with chronic pain conditions.
MAOIs are known to be less effective than other antidepressants for treating depression or anxiety disorders in general.
However, they are still used as an alternative drug when other antidepressants prove ineffective because of contraindications (e.g., a history of a reaction) or hypersensitivity (e.g., an allergy) to the drugs they contain.
Modafinil has been shown to be effective as an antidepressant without worrying about its side effects such as an increase in blood pressure and heart rate.
Only limited research on modafinil in treating depression has been done so far, and it is not yet clear whether it works via different mechanisms than the SSRI class of antidepressant medications.
However, the preliminary evidence suggests that modafinil can improve mood without causing fatigue symptoms and is, therefore, an acceptable choice as an alternative antidepressant at this time.