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Can You Take Wellbutrin & Prozac Together?

Daniel Lieberman

Reviewed by Daniel Z. Lieberman, MD

Written by Vanessa Gibbs

Published 03/24/2023

Updated 08/24/2024

More isn’t always better — especially when it comes to mental health medications. So, can you safely take Prozac® and Wellbutrin® together? 

In some cases, combining Prozac and Wellbutrin— or the generic versions of fluoxetine, and bupropion, respectively — can improve your symptoms. 

In other cases, it can be dangerous as the combination may increase your risk of seizures or suicidal thoughts. 

There’s not enough research to confidently say the combination is entirely safe. So you should get the go-ahead from a healthcare provider before combining Wellbutrin and Prozac. 

Read on for the pros, cons, and everything else you need to know about combining these two antidepressants.

Wellbutrin — and the generic bupropion — is an antidepressant. But it doesn’t fit into typical antidepressant classes like selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). 

Instead, it operates as a sort of one-member band for depression treatment known as a dual norepinephrine and dopamine reuptake inhibitor (NDRI).

Uses 

Wellbutrin is approved by the U.S. Food and Drug Administration (FDA) to treat:

  • Major depressive disorder (MDD)

  • Seasonal affective disorder (SAD)

  • Smoking addiction 

It’s prescribed off-label — when a drug is prescribed for something it isn’t FDA-approved for — to treat conditions like: 

  • Obesity 

  • Depression associated with bipolar disorder 

  • Attention deficit hyperactivity disorder (ADHD)

  • Sexual dysfunction due to SSRI antidepressants

And for people who experience sexual dysfunction symptoms as a result of their antidepressants, Wellbutrin can be an alternative option that doesn’t reduce libido (sex drive) or, in men, cause erectile dysfunction.

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How It Works 

Wellbutrin works by stopping certain brain cells from reabsorbing the neurotransmitters norepinephrine and dopamine. This can help to relieve mood symptoms.

Unlike Prozac, it doesn’t influence serotonin — another neurotransmitter that can stabilize your mood. 

Wellbutrin can sometimes help people with depression that isn’t responsive to serotonin-based treatments like Prozac. 

Side Effects 

Common side effects of Wellbutrin include: 

  • Headache or migraine 

  • Nausea or vomiting

  • Constipation

  • Dizziness

  • Agitation and hostility 

  • Dry mouth 

  • Excessive sweating

  • Tremor

  • Insomnia

  • Blurred vision 

  • Confusion 

  • Rash 

  • Auditory disturbances

  • Tachycardia (when your heart beats too fast) and other cardiac arrhythmias (abnormal heartbeats)

Prozac — and the generic fluoxetine — is also an antidepressant. It belongs to the more common class of antidepressants — SSRIs.

Uses 

Prozac is FDA-approved to treat: 

  • Major depressive disorder (MDD) 

  • Obsessive-compulsive disorder (OCD) 

  • Bulimia nervosa 

  • Panic disorder 

It’s prescribed off-label to treat a variety of mental health issues, including: 

  • Generalized anxiety disorders (GAD) 

  • Social anxiety 

  • Dysthymia (a type of long-term mild depression) 

  • Posttraumatic stress disorder (PTSD)

  • Body dysmorphic disorder

  • Binge eating disorder

  • Premenstrual dysphoric disorder (PMDD)

How It Works 

Prozac works by stopping certain brain cells from reabsorbing serotonin. With more serotonin in your system, you may feel relief from depression symptoms

It’s different from Wellbutrin in that it doesn’t affect other brain chemicals. 

Side Effects 

Common side effects of Prozac include: 

  • Nausea 

  • Diarrhea 

  • Dry mouth

  • Dyspepsia (indigestion) 

  • Flu-like symptoms 

  • Pharyngitis (sore throat) 

  • Sinusitis (sinus infection)

  • Asthenia (weakness) 

  • Insomnia

  • Somnolence (drowsiness) 

  • Yawning 

  • Nervousness

  • Anxiety 

  • Sweating

  • Lowered libido 

  • Abnormal dreams 

  • Rash

  • Vasodilation (widening of blood vessels) 

  • Tremor

  • Anorexia (loss of appetite)

Want to learn more? We’ve covered Wellbutrin vs. Prozac in more detail.

Combining Prozac and Wellbutrin can cause side effects and some of the drug interactions can be very serious.

Here’s what may happen: 

  • Increased risk of seizures. Both Prozac and Wellbutrin can individually increase your risk of seizures. 

  • Increased risk of suicidal thoughts. Similarly, both Prozac and Wellbutrin may individually increase your risk of suicidal thoughts.

If you take two medications with the potential to increase your risk of seizures and suicidal thoughts, it’s almost like you’re increasing that risk twice over.

But, before you panic, those potential adverse effects are considered rare. 

Let your prescribing healthcare provider know if you have a history of seizures or suicidal thoughts. They can assess whether taking Wellbutrin and Prozac together is safe for you. 

One more thing to note. Bupropion inhibits the enzyme CYP2D6. This enzyme helps your body break down many drugs, including fluoxetine. 

So, taking bupropion and fluoxetine together could increase how much fluoxetine there is in your system. Your healthcare provider may adjust your dose to account for this.

It all sounds scary, but we weren’t able to find any significant studies showing major adverse reactions to drug interactions between Wellbutrin and Prozac.

It’s not all doom and gloom. There aren’t a ton of studies or clinical trials examining the combination of bupropion and fluoxetine. But from what is available, it looks like there could be some notable benefits to combining the two.

Here’s what combining Prozac and Wellbutrin could do: 

  • Improved sexual side effects. A small 2002 study looked at bupropion alongside several antidepressants, including fluoxetine, for its impact on sexual dysfunction. It found that fluoxetine’s sexual dysfunction side effects were improved by the addition of bupropion to patients’ treatment plans.

  • Increased antidepressant effects. Another 2002 study — this time on rats — looked at the combined use of both medications and found that bupropion and fluoxetine could increase the antidepressant effects of one another. Fluoxetine increased the impact of bupropion’s dopamine and norepinephrine effects. 

Potential benefits and severe side effects noted, how dangerous is this combination, really? We can’t say for sure, but either way, the medications should only be taken together under the supervision of a healthcare professional.

A 2006 review examined various SSRI antidepressants in combination with bupropion (though they didn’t mention fluoxetine specifically). 

They found that bupropion was “generally well tolerated” alongside SSRIs and may increase the antidepressant effects of antidepressant medications while reducing certain side effects — similar to the studies we mentioned above on the Prozac and Wellbutrin combination. 

That review, however, stopped short of a recommendation. The researchers noted that further studies examining long-term effects, optimal dosage, and the amount of time it’s safe to combine these medications did not yet exist.

It’s difficult for us to offer concrete recommendations. While the limited study data does suggest that Wellbutrin and Prozac in combination could help with treatment-resistant depression or sexual side effects, those studies can’t speak to your individual needs. 

Our advice? Get medical advice from a healthcare provider. The benefits of taking Wellbutrin and Prozac may outweigh the risks, but that’s a decision that should be made based on your individual circumstances.

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Taking one antidepressant is a big step toward better mental health. But can you add a second medication to an antidepressant to get a step closer? 

Wellbutrin and Prozac may be an option for you. There are some potential benefits of taking the antidepressants together, but there are also some potential risks.

Here’s what to keep in mind:

  • Taking Wellbutrin and Prozac may have some benefits. For some, the combination may improve Prozac’s sexual side effects or offer more relief from depressive symptoms compared to taking one medication alone. 

  • It may increase your risk of seizures or suicidal thoughts. Let your healthcare provider know if you have a history of seizures or suicidal thoughts — as well as any other medical conditions. Beyond this, the combo may increase how much Prozac stays in your system. 

  • A healthcare provider can give you personalized advice. There’s not much research on taking the two drugs together, but a healthcare provider can let you know if it’s safe for you or if other medications would be more suitable. 

BTW, if you’re thinking about taking two medications because one isn’t solving the problem, it may be time to reevaluate your treatment options.

There are plenty of options available. Your healthcare provider may suggest dosage changes, additional medications, or new medications altogether. 

They may also recommend therapy and lifestyle changes to better manage your symptoms of depression or other mental health issues. 

If you’re not sure where to begin, check out our mental health resources to explore therapy, medication, and expert guidance — all available online. 

10 Sources

  1. Fava M, et al. (2003). Switching to bupropion in fluoxetine-resistant major depressive disorder. https://pubmed.ncbi.nlm.nih.gov/12839429/
  2. Fluoxetine tablets, for oral use. (2017). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202133s004s005lbl.pdf
  3. Huecker MR, et al. (2023). Bupropion. https://www.ncbi.nlm.nih.gov/books/NBK470212/
  4. Kennedy SH, et al. (2002). Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. https://pubmed.ncbi.nlm.nih.gov/11926715/
  5. Li SX, et al. (2002). Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats. https://pubmed.ncbi.nlm.nih.gov/11804614/
  6. National Alliance on Mental Illness. (2016). Fluoxetine (Prozac). https://www.nami.org/about-mental-illness/treatments/mental-health-medications/types-of-medication/fluoxetine-prozac/
  7. Sohel AJ, et al. (2024). Fluoxetine. https://www.ncbi.nlm.nih.gov/books/NBK459223/
  8. Stahl SM, et al. (2004). A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/
  9. Wellbutrin (bupropion hydrochloride) tablets, for oral use. (2017). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018644s052lbl.pdf
  10. Zisook S, et al. (2005). Use of bupropion in combination with serotonin reuptake inhibitors. https://pubmed.ncbi.nlm.nih.gov/16165100/
Editorial Standards

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at [email protected]!

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Daniel Z. Lieberman, MD

Dr. Daniel Z. Lieberman is the senior vice president of mental health at Hims & Hers and of psychiatry and behavioral sciences at George Washington University. Prior to joining Hims & Hers, Dr. Lieberman spent over 25 years as a full time academic, receiving multiple awards for teaching and research. While at George Washington, he served as the chairman of the university’s Institutional Review Board and the vice chair of the Department of Psychiatry and Behavioral Sciences.

Dr. Lieberman’s has focused on , , , and to increase access to scientifically-proven treatments. He served as the principal investigator at George Washington University for dozens of FDA trials of new medications and developed online programs to help people with , , and . In recognition of his contributions to the field of psychiatry, in 2015, Dr. Lieberman was designated a distinguished fellow of the American Psychiatric Association. He is board certified in psychiatry and addiction psychiatry by the American Board of Psychiatry and Neurology.

As an expert in mental health, Dr. Lieberman has provided insight on psychiatric topics for the U.S. Department of Health and Human Services, U.S. Department of Commerce, and Office of Drug & Alcohol Policy.

Dr. Lieberman studied the Great Books at St. John’s College and attended medical school at New York University, where he also completed his psychiatry residency. He is the coauthor of the international bestseller , which has been translated into more than 20 languages and was selected as one of the “Must-Read Brain Books of 2018” by Forbes. He is also the author of . He has been on and to discuss the role of the in human behavior, , and .

Education

  • 1992: M.D., New York University School of Medicine

  • 1985: B.A., St. John’s College, Annapolis, Maryland

Selected Appointments

  • 2022–Present: Clinical Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2013–2022: Vice Chair for Clinical Affairs, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2010–2022: Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2008–2017: Chairman, George Washington University Institutional Review Board

Selected Awards & Honors

  • 2022: Distinguished Life Fellow, American Psychiatric Association

  • 2008–2020: Washingtonian Top Doctor award

  • 2005: Caron Foundation Research Award

Publications

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