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Provigil (Modafinil) For Depression: An Effective Off-Label Treatment

Provigil (Modafinil) is a eugeroic drug that was originally approved in 1998 for the treatment of excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea.  Despite never attaining FDA approval for the treatment of depression, many anecdotal reports highlight the efficacy of Provigil as an antidepressant.  The drug tends to improve energy levels, decrease fatigue, and combat slow psychomotor activity – all symptoms of major depression.

The mechanism of action associated with Provigil hasn’t been fully deciphered, but it is believed to elicit a variety of effects including: minor dopamine reuptake inhibition (DRI), increase histamine in the hypothalamus, and stimulate orexin receptors.  It also is thought to increase activity in glutamatergic circuits, while simultaneously inhibiting GABAergic activity, and enhance a process called electronic coupling.

It may also slightly increase levels of norepinephrine and serotonin in certain regions of the brain.  Its unique mechanism is also believed to enhance electronic coupling, which may increase gamma waves – characterized as brain waves responsible for processing of information and perception of reality.  The combination of the neural alterations as a result of administration of Provigil tends to noticeably reduce or completely reverse depressive symptoms in certain individuals.

Provigil For Depression: An Effective Off-Label Treatment

Researchers began analyzing Provigil as a treatment for depression due to the fact that it is stimulatory, and thus should help alleviate fatigue-based symptoms associated with depression.  Many individuals with depression complain of excessive daytime sleepiness, chronic fatigue, low energy, and sleepiness.  Provigil is a wakefulness-promoting agent and theoretically should help combat the fatigue and “brain fog” (psychomotor slowing) associated with depression.

Although Provigil hit the market in 1998, it was being investigated for its potential as an antidepressant augmentation strategy in 2000.  It has since been shown to be a highly effective adjunct when used in combination with an SSRI.  This has made some individuals question whether Provigil could be an effective standalone antidepressant option.

Research Timeline: Provigil (Modafinil) for Depression

Listed below are various research studies analyzing Provigil (modafinil) as an antidepressant.  In nearly every study, Modafinil was noted as significantly improving certain aspects of depressive symptoms.  This occurred in various types of depression including: bipolar depression, major depressive disorder, seasonal affective disorder, and atypical depression.

2000: Research published in 2000 analyzed 7 cases of individuals diagnosed with depression.  Four of the individuals were diagnosed with major depressive disorder (MDD) and 3 were diagnosed with bipolar depression.  In all cases, none of the patients responded to first-line antidepressant treatments.

Provigil (modafinil) was added as an adjunct treatment to their antidepressant.  At clinical doses (100 mg or 200 mg), all patients experienced full or partial remission in depressive symptoms in less than 2 weeks.  Side effects were regarded as being “minimal” and didn’t lead to discontinuation by any of the patients.

Researchers noted that Provigil may be preferred over other psychostimulants as an adjunct due to the fact that it has a lower potential for abuse, and is thus classified as a “Schedule IV” drug.  They also suggested that this drug was especially beneficial among those with fatigue or residual tiredness.  Although 7 patients should be considered “small-scale,” it served as preliminary evidence to further investigate the antidepressant effects of Provigil.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10847314

2004: Another study was published in 2004 that analyzed Provigil among individuals with seasonal affective disorder (SAD), commonly known as “seasonal depression.”  Individuals with seasonal depression tend to experience hypersomnia (excessive sleepiness) and become more depressed as a result of seasonal changes, typically during the winter months.  In most cases, the depression is caused by a lack of bright light exposure as a result of shorter days and poor sunlight.

Provigil (modafinil) was administered to 12 patients with seasonal affective disorder (SAD) starting at 100 mg.  It was then increased in some of the patients after one week to 200 mg.  Of these patients, 5 received the 100 mg dose, while 7 received the 200 mg dose.  Provigil significantly improved seasonal affective disorder (SAD) among the 9 patients that completed treatment.

In fact, it was found to improve symptoms within just 1 week of treatment and maintained efficacy through 8 weeks.  The symptoms of seasonal affective disorder were evaluated with various scales, one of which was the SIGH-SAD protocol.  With this protocol, the higher the score, the more severe the symptoms.

Average pre-Provigil [baseline] test scores of SIGH-SAD were 37.2, but after 8 weeks of treatment with Provigil they significantly dropped to an average of 17.1.  Researchers noted that response rates were 67% on the standard 29-item SIGH-SAD test, whereas they were 100% on the atypical 8-item SIGH-SAD test.  Provigil significantly decreased fatigue, improved wakefulness, and was considered well-tolerated for those with seasonal depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15306145

2004: Another study published in 2004 investigated whether Provigil was an effective adjunct treatment for individuals with depression.  Participants for this study were individuals with a history of major depressive disorder with partial responses on therapeutic doses of antidepressants.  All participants had mentioned that they were extremely fatigued or experienced excessive sleepiness upon clinical assessment.

Among 31 patients, Provigil was administered at doses ranging between 100 mg and 400 mg over the course of 1 month (4 weeks); they still took their initial antidepressant.  All participants were analyzed at 2-week intervals using various depression rating scales (e.g. HDRS, BDI, CGI).  Following the 1 month trial, all patients significantly improved on all three rating scales, as well as secondary measures of fatigue.

Researchers also noted that patients experienced neuropsychological performance enhancement.  This cognitive enhancement was noted by significant improvements in Stroop Interference Test scores after 4-weeks.  Authors of this study concluded that Provigil (modafinil) may be a well-tolerated adjunct treatment for patients with major depressive disorder.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/14709953

2005: As Provigil gained recognition for its wakefulness-promoting effect, researchers began determining whether it would improve outcomes of those who respond poorly to antidepressant therapy.  Researchers conducted an open label study analyzing Provigil’s effect as an adjunct to ongoing antidepressant treatment.  Provigil was administered within the dose range of 100 mg to 400 mg.

In a total of 21 participants, 43% experienced significant reductions in depressive symptoms and remission rates.  Those who responded well to Provigil scored lower on ratings for depression, hostility, anxiety, somatization, obsession, and psychoticism.  This was early evidence highlighting the efficacy of Provigil as an adjunct.

  • http://www.ncbi.nlm.nih.gov/pubmed/16208839

2005: Researchers in 2005 gathered data on patients diagnosed with major depression that had been administered modafinil upon failed responses to traditional antidepressant treatments.  During this study, researchers utilized various rating scales such as the Beck Depression Inventory, Zung Self-Rating Depression Scale, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale.  They reviewed cases of 45 individuals that were treated with modafinil over the course of 9 months.

The average dose of modafinil was estimated at 184.3 mg per day (ranging from 50 mg to 450 mg).  For all 45 patients, significant improvements were noted on all four rating scales after 2 weeks of treatment and were maintained after 90 days (3 months) of treatment.  A total of 15 patients were on modafinil monotherapy, whereas the other 30 were using it as an adjunct.

Based on this evidence, researchers concluded that modafinil treatment may be beneficial to those with depression, even upon failed response to traditional first-line options.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16035049

2006: Another study analyzed the usage of modafinil (Provigil) as a standalone treatment option for atypical depression.  This was considered a 12-week, open-label study followed by a 12-week double-blind, randomized parallel treatment period with either modafinil or a placebo.  To qualify for the study, an individual must have been between 18 and 65 years of age.

They also needed to meet DSM criteria for major depression with atypical features, have a minimum score of 18 on the HAM-D-29 (with atypical features), a CGI-S score of 4 or more, written informed consent, and a negative serum pregnancy test.  A total of 89 participants were screened for the study, but only 66 met criteria.

Of those 66 participants, only 53 completed the open-label phase; 13 dropped out due to adverse reactions, time commitments, unrelated chest pain, worsening depression, and/or unknown reasons.  Of the 53 participants that completed the open-label phase, 50 demonstrated slightl improvement  in depressive symptoms and continued with the second 12-week randomized, double-blind phase.  During the second 12-weeks, a total of 24 patients were assigned to modafinil, while 26 were given a placebo.

A total of 41 participants were able to complete the full double-blind phase: 22 on modafinil and 19 on the placebo.  Those taking the modafinil experienced significant improvement in their HAM-D-29 scores compared to baseline. The scores dropped from 34.0 to 9.7 by week 12 during the open-label phase, indicating a significant reduction in depression.

During the second randomized 12-week phase, the HAM-D-29 scores dropped from 33.6 (baseline) to 8.7 (after 12 weeks).  Although there was no significant difference between the HAM-D-29 scores of those receiving the modafinil (Provigil) compared to the placebo group, both had significantly improved.  Those taking the Provigil during the randomized phase also significantly improved based on various subscales including: SCL-90 anxiety/depression subscales and the overeating subscale.

Researchers concluded that modafinil is safe and effective for the treatment of atypical depression.  Although it wasn’t superior to a placebo, those taking Provigil for the full 24 weeks maintained their antidepressant effect after 12 weeks.  Authors emphasized a future need for larger-scale, longer-term, double-blind, placebo-controlled, parallel studies.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16855454

2006: A study published in 2006 researched the effects of modafinil (Provigil) augmentation to an SSRI among individuals diagnosed with major depressive disorder, excessive sleepiness, and fatigue.  This study was conducted over a 12-week period and was considered “open-label.”  Following the initial 12-week open-label portion of the study, 8-weeks of placebo-controlled research was conducted.

The dosage of Provigil administered was 100 mg to 400 mg per day, with the median dose being 300 mg.  Patients were assessed using sleepiness scales, fatigue inventories, and depression rating scales (i.e. Hamilton Rating Scale / Montgomgery-Asberg Scale).  A total of 194 participants completed the study and 70% experienced significant improvement with modafinil compared to their baseline rating scores.  Researchers noted that 12-weeks of modafinil augmentation improved mood, while simultaneously reduced fatigue and sleepiness.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16520686

2007: In 2007, a study was conducted analyzing the effects of Provigil on 85 patients with bipolar depression.  A total of 41 were assigned Provigil as an adjunct treatment, while 44 were administered an adjunct placebo.  The patients were analyzed over the course of 6 weeks and their results were measured as a result of scores on the Inventory of Depressive Symptoms (IDS).

Changes in IDS scores as determined by clinicians were significantly superior in those receiving the Provigil compared to those receiving a placebo.  Depressive symptoms significantly improved after just 2 weeks among those receiving the Provigil, and the improvement was maintained through the remainder of the 6-week period.  Response and remission rates were greater in the Provigil group compared to the placebo group, suggesting that doses of 100 mg to 200 mg may improve bipolar depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17671288

2013: A meta-analysis was published in 2013 analyzing responses to modafinil (Provigil) as an adjunct in cases of unipolar and bipolar depression.  This meta-analysis specifically assessed the efficacy and tolerability of Provigil as an adjunct to first-line treatment options.  They only included randomized controlled-trials (RCTs) with modafinil in cases of unipolar or bipolar depression as diagnosed by the DSM-IV.

Data was analyzed from 6 randomized controlled-trials with a total of 910 participants diagnosed with either major depressive disorder (568 patients) or bipolar depression (342 patients).  This meta-analysis suggested that modafinil significantly improved depression scores as well as remission rates.  The treatment outcomes were favorable in cases of major depressive disorder and bipolar depression, with no differences between each type of depression.

Researchers noted that Provigil significantly improved fatigue-based symptoms and adverse reactions didn’t differ significantly from a placebo.  This suggests that Provigil is a well-established adjunct option for depression, and is especially effective at combating depression-related fatigue.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24330897

How Provigil (Modafinil) Treats Depression: Multi-Faceted Mechanisms

Provigil has a unique mechanism of action in that it elicits a variety of neural changes, all of which may contribute to its antidepressant effect.  Although it isn’t clinically approved to treat depression, the aforementioned research indicates that it is a highly effective adjunct.  Provigil is believed to treat depression via CNS stimulation (reducing fatigue) and other neurotransmission alterations.

Cognitive enhancement: Many individuals with depression suffer from “brain fog,” psychomotor slowing, and cognitive impairment.  This impairment may result from abnormal brain wave activity, deficiencies in neurotransmitters, and/or insufficient regional activation.  Provigil is a well known “nootropic” or cognitive enhancer.  Improved mental performance may equate to confidence in social situations and/or improved work/school performance – both of which may reduce depression.

CNS stimulation: Those with depression often have reductions in CNS stimulation – they are understimulated.  This lack of stimulation results in low energy, depressive mood, and excessive fatigue.  Provigil has the ability to combat this by dramatically increasing CNS stimulation.  This results in heightened vigilance, energy, and speeds psychomotor activity.

Dopamine reuptake inhibition: Although the dopamine reuptake inhibition associated with Provigil may be minor – it is worth noting.  The drug increases extracellular concentrations of dopamine, possibly just enough to help reduce depressive symptoms.  For those that want to slightly increase dopamine, Provigil may be helpful.

Electronic coupling: In the inferior olivary nucleus, Provigil has been shown to increase electronic coupling between cortical interneurons and nerve cells.  The significant enhancement of electronic coupling is believed to increase “gamma waves,” resulting in improved intracellular communication.  The increase in potency of neural communication as a result of electronic coupling may promote improved cognition, perception, and ultimately – mood.

Glutamatergic circuitry: Glutamate is a neurotransmitter involved in learning, memory, and cognitive function.  Provigil is believed to increase activity of glutamate circuits as discovered in rodent studies.  The activation of glutamatergic circuitry may aid in restoring proper sleep-wakefulness cycles and improve mood.

GABA inhibition: In a study conducted among humans with narcolepsy, modafinil was analyzed for its effect on cortical excitability.  Researchers suggested that since short-latency intracortical inhibition is directly related to narcolepsy and is thought to be a result of cortical hypoexcitability.  Administration of modafinil may promote wakefulness by decreasing neurotransmission of GABA(A).

Monoamine increases: Provigil affects various neurotransmitters to a minimal extent including norepinephrine and serotonin (in addition to dopamine).  Dopamine notably increases in the striatum and nucleus accumbens. Norepinephrine increases have been noted in the hypothalamus and ventrolateral preoptic regions, while serotonin tends to increase in the amygdala and prefrontal cortex.

Orexin expression: Animal studies suggest that orexin dysfunction may contribute to depression.  Provigil is believed to stimulate orexin receptors (OX1 and OX2), which increases orexin activity, and thus may reduce certain depressive symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17640897
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20810311
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10088135

Optimal Scenarios to Use Provigil for Depression

Not just anyone with depression can go get a prescription for Provigil.  Though the drug is relatively safe and has a low potential for abuse, some psychiatrists and doctors refuse to prescribe it.  Below are some optimal scenarios for those considering Provigil.

  • Apathy: Evidence from some studies suggests that Provigil significantly reduces apathy.  If apathy is a dominant characteristic of your depression, Provigil may help.  A case study of one woman with refractory bipolar depression experienced a drop in her “apathy” rating from 61 to 31 after 16 weeks of treatment.
  • Atypical depression: Provigil has been studied as a monotherapy treatment for those suffering from atypical depression.  If your depression is classified as atypical, there is some evidence to suggest that trying Provigil may not be a bad idea.
  • Brain fog: If you have comorbid “brain fog” or ADHD along with depression, Provigil may significantly help. (Read: Provigil for ADHD).  It is a known cognitive enhancer and is believed to speed up brain waves rather than amplify slow waves.  Many standard antidepressants may exacerbate this cloudy thinking, whereas Provigil usually gets rid of brain fog.
  • Comorbid narcolepsy: If you have depression with comorbid narcolepsy, obstructive sleep apnea (OSA), or shift work sleep disorder – you are the perfect candidate to try Provigil.  It is approved for these conditions and is regarded as a first-line option.  Those who have depression with low energy, hypersomnia, or significant fatigue may also benefit from Provigil.
  • Seasonal affective disorder: Individuals with “seasonal depression” may benefit from taking Provigil during the winter months to combat fatigue, low energy, and psychomotor slowing.  There is some preliminary evidence to suggest that Provigil can alleviate symptoms of seasonal affective disorder.
  • Treatment-resistant depression: Those with “refractory” forms of depression that do not respond to traditional treatments may want to consider Provigil.  Most people regard it as being safer, with less side effects and withdrawal symptoms compared to other adjunct options.  Assuming you have a treatment-resistant form of depression, Provigil may be worth trying for its unique mechanism of action.

Why Provigil may help your depression

The most substantial evidence to suggest Provigil (modafinil) will help your depression can be derived from research trials.  Most notably, Provigil promotes energy increases, is fast-acting, and enhances cognitive function.  These effects derived from Provigil may mitigate various neurological, psychological, and behavioral aspects of depression.

  • Clinical trial efficacy: An array of evidence suggests that Provigil is effective for the treatment of depression.  This evidence stems from clinical trials dating back to the early 2000s.  In nearly every trial, researchers noted substantial benefit from Provigil among individuals with various types of depression.
  • Cognitive enhancement: Provigil is a proven cognitive enhancer, which can be helpful for those who are depressed.  Those with major depression tend to have cognitive impairment and psychomotor slowing as a result of neurotransmitter deficits and abnormal cerebral blood flow.  Provigil may offset any cognitive impairment associated with a person’s depression.
  • Energy increase: Those with depression often have low energy and in severe cases, they may be unable to get out of bed.  If you are bedridden, constantly sleepy, or fatigued as a result of your depression, Provigil should give you the necessary “kick” to get out of bed.  Think of it as providing a strong jolt of energy.
  • Fast-acting: Most people find that Provigil is fast-acting in that they experience noticeable reductions in depressive symptoms within just 2 weeks.  Unlike traditional antidepressants that take long to work (6 to 8 weeks), Provigil can produce improvements upon the first day of usage.  This is fast-acting effect can be extremely helpful to someone that can’t afford to wait another month for relief.
  • Mood improvement: Many people have used Provigil as a standalone treatment for depression with varying degrees of success.  Although it doesn’t significantly inhibit the reuptake of serotonin (like an SSRI) it is thought to impact a broad spectrum of neurotransmitters and receptors.
  • Motivation: A common symptom of severe depression is “avolition” or lack of motivational drive.  Provigil has the potential to increase motivation and goal-oriented behavior via CNS stimulation and more specifically minor dopaminergic effects.  While it may not kick-start motivation as significantly as Adderall, it will likely help.
  • Productivity: Those with depression often have a tough time holding down a job due to depression-induced performance impairment.  Even if a person with depression manages to land a job, their productivity may suffer as a result of low energy or brain fog.  Provigil should increase energy and decrease brain fog, ultimately increasing productivity.
  • Refractory depression: If you have refractory depression, Provigil can be an effective adjunct to your antidepressant.  Heck, it may even work better than your current antidepressant and/or serve as an effective monotherapy option.  Those with refractory depression may experience significant benefit should they add Provigil to their existing antidepressant.
  • Side effects: The side effect profile associated with Provigil is considered minimal.  Most common side effects include: headache, nausea, dizziness, and insomnia.  Unlike other antidepressants, this drug won’t affect your sex drive or cause weight gain.
  • Weight loss: Many people have noticed that Provigil and weight loss go hand-in-hand.  This is due to the fact that Provigil stimulates the CNS, which increases your metabolism, gives you energy to work out, and decreases appetite as a result of dopaminergic effects.  The weight loss may not be significant, but it may be enough to improve mood.
  • Withdrawal: Most medical professionals suggest that there are zero Provigil withdrawal symptoms.  While it is unlikely that there are no significant symptoms, the discontinuation effects appear to be significantly less debilitating than those associated with SSRIs and other modern-day antidepressants.

A “cascade effect” from Provigil?

It is important to also consider the potential of an indirect “cascade effect” as a result of Provigil usage.  Provigil may not fully alleviate depressive symptoms as a standalone option or as an adjunct, but it may reduce fatigue, improve cognition, and enhance productivity enough to have carryover in other areas of life.  This may lead to improvements in mood and life satisfaction.

  • Cognitive function: Consider the improvement in cognitive function as an indirect antidepressant effect.  Improved cognition may result in better performance at school, work, or even in social situations.  Your brain may be primed with ideas and in a state of peak performance.  This optimal state of performance leads to improved relationships with others, increased earnings on the job, better grades at school, and ultimately more satisfaction.
  • Productivity: Provigil has potential to amplify productivity, and is often used by executives off-label to increase performance.  This means getting more work done in a shorter amount of time due to the cortical enhancement derived from Provigil.  The more you accomplish while taking Provigil has potential to improve your life in: earning potential, learning a new skill, getting a better job, or accomplishing more throughout the day – all of this may result in less depression.
  • Energy increase: This medication is known to increase energy, which can be used to accomplish more throughout the day.  You’re no longer sitting in bed all day feeling depressed, rather you have enough energy to go outside, apply for jobs, get to the gym, fit in a workout, or get more accomplished at work.  This increase in energy is helpful and can be channeled to reduce depression in many ways.
  • Weight loss: Many people with depression are overweight as a result of inadequate physical activity, overeating, and a poor diet.  Provigil may result in weight loss as a result of turning your brain on, making you realize what foods are good for you and what ones aren’t.  Additionally the increased energy, decreased appetite, and increased metabolism are a recipe for weight loss.  Losing a little bit of weight from this medication has the potential to improve a person’s mood.

Why you may want to avoid Provigil for depression

It should be known that no medication is a utopian treatment for depression, and Provigil is no exception.  There are several reasons that a person may want to avoid using Provigil for depression including: anxiety, side effects, and undocumented long-term effects.

  • Anxiety: Due to the fact that this drug promotes wakefulness and is stimulating, it may exacerbate underlying anxiety.  If you have depression with a comorbid anxiety disorder, you may find that you cannot tolerate Provigil because it makes you feel too nervous.
  • Dependence: Although you’re less likely to become dependent on Provigil than you are a Schedule II psychostimulant like Adderall, dependence is still possible.  This means that you may eventually come to rely on Provigil just to function normally.  The enhancement and antidepressant effect may subside after years of treatment.
  • Long-term effects: The long-term effects associated with Provigil are relatively unknown due to the fact that the drug hit the market in the late 1990s.  In the future researchers will know more about long-term safety, but as of now it remains undocumented.  That said, most preliminary evidence suggests that it is likely to be safe.
  • Unknown mechanism: The mechanism of action isn’t fully known, making some reluctant to try this medication.  It is believed to elicit a broad spectrum of neural changes, making it difficult to pinpoint precisely how Provigil works.
  • Side effects: Some people experience debilitating side effects and adverse reactions (e.g. skin rashes) from Provigil.  While side effects aren’t as common with Provigil as other antidepressants, there is potential for an adverse reaction.
  • Withdrawal: The withdrawal may be more severe than medical research suggests, leading to low energy, fatigue, and sleepiness upon discontinuation.  Assuming there is no biological free lunch, and that “what goes up, must come down,” the withdrawal process may be debilitating for certain individuals.  This is especially true for those who became dependent upon the medication for functioning.

How does Provigil compare to Adderall for depression?

Those looking at adjunct options may discover Adderall for depression.  In fact, Adderall may still remain the more popular option in many circles.  My psychiatrist considers them to be similar drugs, and suggested that since I responded to Adderall, there was no need to even try Provigil.  Other psychiatrists may actually prefer Provigil over Adderall due to the fact that it’s less addictive.

I’ve written up a comparison of Provigil vs. Adderall that you can check out for further information.  Adderall elicits a more potent dopaminergic effect, is subject to abuse, dependence, and is much more likely to have a debilitating withdrawal.  Though Adderall has been on the market longer and has been involved in more research, most evidence suggests Provigil is likely safer.

How does Nuvigil compare to Provigil for depression?

Nuvigil is considered an upgraded version of Provigil in that it contains only the R-enantiomer of modafinil, whereas Provigil contains both the R-enantiomer and S-enantiomer.  For this reason, Nuvigil is believed to have a cleaner, longer-lasting effect than Provigil.  It is believed to pack a more potent dopaminergic effect by comparison and has a quicker onset of action.

These two drugs are very similar, if you want more information you can read the comparison I’ve written of Nuvigil vs. Provigil.  Some individuals may respond better to Provigil over Nuvigil, while others will find that Nuvigil is slightly (or significantly) better than Provigil based on their individual physiology.

Verdict: Provigil helps many cases of depression

Based on the amassed research, Provigil warrants further investigation as an antidepressant –  particularly in cases of depression associated with: narcolepsy, shift work, chronic fatigue, excessive daytime sleepiness, seasonal affective disorder (SAD), and atypical depression.  Although there aren’t many large scale randomized, placebo-controlled trials that have been conducted, nearly all of the research suggests Provigil is an effective antidepressant.  At the very least, it is a highly effective adjunct, and in some cases it may be an effective monotherapeutic option.

Don’t consider Provigil a utopian antidepressant, but consider it effective for combating many symptoms associated with depression such as excessive fatigue, sleepiness, and psychomotor slowing.  At the very least it will kick-start your physical energy and mental performance, offsetting many neurological, psychological, and physical symptoms associated with depression.  It may not fully treat your depression, but it seems as though its likely to help with something.

Have you tried Provigil for depression?

If you’ve had the opportunity to try Provigil, have you noticed any antidepressant effects?  Did the drug improve your mood or any symptoms associated with your depression?  If so, what were the biggest improvements you experienced while taking Provigil?  Feel free to share the dose that you took (or are taking) as well as how long you were on it (or have been on it).

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7 thoughts on “Provigil (Modafinil) For Depression: An Effective Off-Label Treatment”

  1. My story is somewhat different from those I’ve read here. My primary physician put me on bupropion sr (150 mg bid) for what he labeled “minor depression”. I’m still taking it 12 years later. In 2001 I was diagnosed with obstructive sleep apnea, and responded somewhat well to CPAP therapy which I have utilized to this day with moderate success.

    In about 2007 or 2008 I complained of daytime sleepiness despite the CPAP, and ended up on 200 mg of modafinil. About 2 years I switched sleep physicians. The former was a pulmonologist certified in sleep, the new doctor is a neurologist also certified in sleep medicine. She began to question my modafinil use. “You don’t have to take it every day.”

    I ignored her for over a year, but because she repeated the suggestion that I only take it “when I need it,” whatever that means. I tapered to 5 days a week, and slowly over the last 6 months have reduced to intermittent use 2 or 3 days a month. Recently I’ve noticed increasing brain fog, and disorder in my life, ignoring life functions like laundry or housekeeping.

    This has prompted me to do some reading, and while not yet confirmed, I think that nearly eliminating the daily modafinil has increased my minor depression symptoms. While I won’t see my sleep doctor for several weeks, I intend to slowly increase my modafinil use until it is daily, or at least the skipped days might be rare, wish me luck.

  2. Modafinil is the only western medication I’ve taken that works… for lethargic depression, anhedonia, chronic fatigue, and ADD. 100 mgs at the same time daily. Oddly enough, my essential tremors have been reduced dramatically. Increased dopamine? Don’t want to put any more details on a public sight, but if someone was looking for the poster child for Modafinil, that would be me. Haven’t found any reliable info on how moda affects cortisol, and would appreciate some sources.

  3. Modafinil has changed my life in many ways: increased motivation and activity,lower anxiety and depression, much better concentration and interest in projects. I also take 40mgs of prozac, but only noticed a considerable difference in lowering depression after taking modafinil this last six months. When I increased it to 600mgs modafinil per day was when the big difference came for me. Many have high tolerances which require higher dosages. Doctors need to recognize this for patients.

  4. Tormented life until a doctor prescribed provigil. I have Treatment Resistant Severe Depression and am on SS Disability for same.

  5. This medication has changed my life. My doctor prescribed 100 mg to help with my focus at work. I didn’t even realize this could be used to treat depression until it helped me with that. The suicidal ideation I’d been battling for decades ended within two days of taking this med. Something that had become a security blanket over the years became what it actually is: crazy. It stopped my obsessive thoughts. Gave me control of my moods. Now when I’m interrupted at work I can get back into what I was doing without my mind wandering like a helpless, lost cow. It’s absolutely amazing.

  6. I have tried modafinil which is the generic of provigil… and I felt the best I have ever felt in my life at 300 mg it was amazing. I did get a little more anxiety at lower doses but man at 300 I was on top of the world and I was up playing games until 5 am, drinking beer of course. That being said I have not tried it while I was depressed. Right now I have some anxiety so I do not want to try it with that. But I would think it can help in a depressive episode.

  7. Why is Provigil not approved by Medicare without a sleep study? I suffer from depession and daily fatigue not sleep apnea.


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