Modafinil and Wellbutrin | What You MUST Know

Tomas Thorne

Last Updated: February 18, 2023

Modafinil and Wellbutrin

Curious about the effects of taking modafinil and Wellbutrin? This article is a must-read.

Modafinil is a wakefulness agent for sleep disorders, while Wellbutrin is the brand name for bupropion, an antidepressant.

Although they are made for completely different purposes, there may be some overlap between them — especially in people who concurrently have a sleep disorder and a mood disorder.

This article reviews what we currently know about modafinil and Wellbutrin.

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Disclaimer: The contents of are for informational and educational purposes only. We do not provide legal advice. Likewise, we do not provide medical advice, diagnosis, or treatment. Please consult your physician prior to consuming Modafinil or related nootropics. Your access to is subject to our full Disclaimer and Terms of Use.

What Is Modafinil?

Modafinil is a prescription drug that is used to increase wakefulness in people with sleep disorders like narcolepsy, shift work disorder, and sleep apnea. It’s also used for a number of “off label” uses, including for people with depression, attention deficit hyperactivity disorder (ADHD), and more. [1, 2]

In addition, modafinil is a powerful and well-known nootropic agent — meaning it provides cognition-enhancing benefits above and beyond simply promoting wakefulness. [3]

Modafinil Benefits

Here are some of the benefits of modafinil:

  • Energy and alertness. The primary use of Modafinil is for increasing energy and wakefulness in people with sleep disorders. However, it’s also used to combat fatigue in other conditions like depression and multiple sclerosis. It’s also been used with good effects to improve alertness in sleep deprived, healthy fighter pilots. [4, 5, 6]
  • Focus and concentration. There are many anecdotal reports of improved focus and concentration on modafinil, which is why it’s of interest to nootropics researchers. Published research has also noted that modafinil helps with focus and concentration, as well. [7, 8]
  • Decision making and test performance. One study noted that 200 mg of modafinil one time could improve pattern recognition, executive function, and decision making. [9]
    Mood and confidence. Modafinil in combination with antidepressants has been shown to help put depression in remission. There are some anecdotal reports that modafinil increases feelings of confidence as well, and this finding has also been noted in scientific literature [6, 10].

Modafinil Side Effects and Safety

The U.S. National Library of Medicine lists the following potential side effects for modafinil: [1]

  • “headache
  • dizziness
  • difficulty falling asleep or staying asleep
  • drowsiness
  • nausea
  • diarrhea
  • constipation
  • gas
  • heartburn
  • loss of appetite
  • unusual tastes
  • dry mouth
  • excessive thirst
  • nosebleed
  • flushing
  • sweating
  • tight muscles or difficulty moving
  • back pain
  • confusion
  • uncontrollable shaking of a part of your body
  • burning, tingling, or numbness of the skin
  • difficulty seeing or eye pain”

Additionally, they list the following severe side effects that require urgent medical attention: [1]

  • “rash
  • blisters
  • peeling skin
  • mouth sores
  • hives
  • itching
  • hoarseness
  • difficulty breathing or
  • swallowing
    swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
  • chest pain
  • fast, pounding, or irregular heartbeat
  • frenzied, abnormally excited mood
  • hallucinating (seeing things or hearing voices that do not exist)
  • anxiety
  • depression
    thinking about killing or harming yourself”

The most common side effects reported by nootropics researchers appear to be headache, loss of appetite, and insomnia.

Researchers should also note that it’s important to review subjects other prescription medications, pre-existing medical conditions, and pregnancy or breastfeeding status before administering modafinil.

Wellbutrin and Modafinil

Modafinil and Wellbutrin

Wellbutrin, or bupropion, is a commonly-used prescription antidepressant drug. Because modafinil shows promise at reducing fatigue in people with depression, it is sometimes prescribed off-label to people who are already taking Wellbutrin. [11]


Several studies have investigated the potential of modafinil in combination with antidepressants, especially in people who don’t seem to fully respond to antidepressants.

One review of six randomized controlled trials noted that the addition of modafinil to depression therapy significantly helped to reduce fatigue and improve depression remission, and that the side effects were no different than those of a placebo. [10]

Additionally, one case report of a 30 year old woman taking Wellbutrin for depression detailed that she had a good response to the addition of modafinil. Prior to starting modafinil she was dealing with excessive fatigue during the day that was affecting her quality of life. [12]

After taking 200 mg of modafinil per day for just 2 weeks, she reported that her energy levels had significantly improved. Additionally, her depression symptoms had decreased in severity to the point that she was considered to be in remission. Even 6 months after starting modafinil, she remained in remission. No side effects were listed in the case report. [12]

Potential side effects

There appear to be no interactions between Wellbutrin and modafinil. However, subjects may experience side effects of both modafinil and Wellbutrin if they’re taking both drugs concurrently. Here are the potential side effects of Wellbutrin (both mild and severe) listed on the U.S. National Library of Medicine website: [11]

  • “drowsiness
  • anxiety
  • excitement
  • difficulty falling asleep or staying asleep
  • dry mouth
  • dizziness
  • headache
  • nausea
  • vomiting
  • stomach pain
  • uncontrollable shaking of a part of the body
  • loss of appetite
  • weight loss
  • constipation
  • excessive sweating
  • ringing in the ears
  • changes in your sense of taste
  • frequent urination
  • sore throat
  • seizures
  • confusion
  • hallucinating (seeing things or hearing voices that do not exist)
  • irrational fears
  • muscle or joint pain
  • rapid, pounding, or irregular heartbeat
  • fever
  • rash or blisters
  • itching
  • hives
  • swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
  • hoarseness
  • difficulty breathing or swallowing
  • chest pain”

Anecdotal reports

Anecdotally, some researchers who have tried Wellbutrin and modafinil together report good results — like boosted energy and mood. Some say that Wellbutrin is more subtle, while the effects of modafinil are more immediately noticeable. Several researchers say that it seems to be a great combination for ADHD and depression, improving mood, energy, focus, and motivation.

However, we’ve seen at least one anecdotal report that modafinil and Wellbutrin together actually caused too much of an increase in energy, leading to insomnia and restlessness. Another researcher noted that the combination made them hyper focused on one task, making it difficult to shift between tasks.

Should they be mixed?

Combining Wellbutrin and modafinil may be extremely beneficial for people who don’t respond well to antidepressants or who are experiencing high levels of fatigue while on depressants. Modafinil can alleviate some of that fatigue and may help with other depressive symptoms as well.

However, because both of these medications require a prescription, it’s important to discuss them with a healthcare provider before combining them.

Wellbutrin and Modafinil

Modafinil and Wellbutrin | Verdict

Modafinil is a wakefulness agent that may also provide a number of other benefits, like improving mood, focus, and memory.

Wellbutrin is an antidepressant used in the treatment of depression.

Modafinil is often added “off label” to depression therapies because it helps to reduce fatigue, and many studies have noted that it can help to put depression in remission in combination with antidepressants. One published case report and many anecdotal reports affirm this, as well.

However, both modafinil and Wellbutrin have side effects, and some people have reported that the combination didn’t work well for them.

Anyone who is interested in combining Wellbutrin and modafinil should open a dialogue with their healthcare provider before taking further steps.


  1. U.S. National Library of Medicine. Modafinil. MedlinePlus website. February 15, 2016.
  2.  Peñaloza RA, Sarkar U, Claman DM, Omachi TA. Trends in on-label and off-label modafinil use in a nationally representative sample. JAMA Intern Med. 2013;173(8):704-706. doi:10.1001/jamainternmed.2013.2807
  3. Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol. 2015;25(11):1865-1881. doi:10.1016/j.euroneuro.2015.07.028
  4. Videbech P. Modafinil i behandling af depression [Modafinil in the treatment of depression]. Ugeskr Laeger. 2012;174(6):348-351.
  5. Brown JN, Howard CA, Kemp DW. Modafinil for the treatment of multiple sclerosis-related fatigue. Ann Pharmacother. 2010;44(6):1098-1103. doi:10.1345/aph.1M705
  6. Caldwell JA, Caldwell JL, Smith JK, Brown DL. Modafinil’s effects on simulator performance and mood in pilots during 37 h without sleep. Aviat Space Environ Med. 2004;75(9):777-784
  7. Kredlow MA, Keshishian A, Oppenheimer S, Otto MW. The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis. J Clin Psychopharmacol. 2019;39(5):455-461. doi:10.1097/JCP.0000000000001085
  8. Repantis D, Bovy L, Ohla K, Kühn S, Dresler M. Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine. Psychopharmacology (Berl). 2021;238(2):441-451. doi:10.1007/s00213-020-05691-w
  9. Müller U, Rowe JB, Rittman T, Lewis C, Robbins TW, Sahakian BJ. Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers. Neuropharmacology. 2013;64(5):490-495. doi:10.1016/j.neuropharm.2012.07.009
  10. Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2013;74(11):1101-1107. doi:10.4088/JCP.13r08560
  11. U.S. National Library of Medicine. Bupropion. MedlinePlus website. February 15, 2018.
  12. Berigan TR. Augmentation With Modafinil to Achieve Remission in Depression: A Case Report. Prim Care Companion J Clin Psychiatry. 2001;3(1):32. doi:10.4088/pcc.v03n0109

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