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Both Wellbutrin (bupropion) and Prozac (fluoxetine) are incredibly popular antidepressants in the United States. In 2017 alone, medical providers approved 24,488,843 prescriptions for bupropion and 25,619,277 for fluoxetine hydrochloride. Patients looking to treat conditions like major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders may wonder what the difference is between these medications. So, when it comes to Wellbutrin vs. Prozac, which comes out on top?


Wellbutrin is the trade name of the drug bupropion hydrochloride. It is an atypical antidepressant, which effectively means it does not fit into other major categories of antidepressants. Experts often classify this drug as a dopamine reuptake inhibitor or medication belonging to the aminoketone class.


The FDA indicates Wellbutrin XL (bupropion hydrochloride extended-release tablets) for the treatment of both MDD and seasonal affective disorder (SAD). Under the trade name Zyban, the FDA approves the use of bupropion hydrochloride sustained-release tablets as smoking cessation aids.


There are some cases where Wellbutrin will not be the right choice for everyone. The FDA states that the following patients should not use this medication:

  • Those with epilepsy or another seizure disorder
  • Those taking any other medication containing bupropion
  • People with hypersensitivities or allergies to bupropion or any other ingredient of Wellbutrin
  • Those being treated for or have a current or prior diagnosis for the eating disorders bulimia or anorexia nervosa
  • Patients “undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines)”
  • Those who currently use, or have used within the past 14 days (2 weeks), a monoamine oxidase inhibitor (MAOI or MAO inhibitor)


Prozac is the trade name of the drug fluoxetine hydrochloride. It is a selective serotonin reuptake inhibitor, or SSRI.


The FDA has approved the use of Prozac for the treatment of MDD, OCD, bulimia nervosa (bulimia), and panic disorder. It may be used along with the drug olanzapine for the treatment of bipolar I depressive episodes and treatment-resistant depression.


The FDA states that the following should not use fluoxetine:

  • Patients who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days (2 weeks) of starting Prozac
  • People undergoing treatment with either linezolid (Zyvox) or intravenous (IV) methylene blue (ProvayBlue)
  • Patients taking pimozide (Orap)
  • Patients taking thioridazine

Wellbutrin vs Prozac – What is the Difference?

While both Prozac and Wellbutrin are antidepressants, they are different drugs belonging to different drug classes (SSRIs and atypical antidepressants, respectively) and work in different ways.

How Do They Work?

As an SSRI, experts believe that fluoxetine works by suppressing the reabsorption of the “feel-good chemical” serotonin. By contrast, experts believe that bupropion works by inhibiting the reuptake of dopamine and perhaps even norepinephrine as well. All three of these neurotransmitters (serotonin, dopamine, norepinephrine) are associated with mood, which explains why both medications are popular antidepressants.

Which is Better?

Which medication works best depends on the individual patient. Both medications are indicated for the treatment of MDD, although they have other uses as well. Patients suffering from bulimia, OCD, and panic disorder would likely benefit more from Prozac. Conversely, patients with SAD would likely benefit more from Wellbutrin.

In some cases, medical providers may recommend combination use of fluoxetine and bupropion to treat depression more effectively and to offset some of the more unpleasant side effects of fluoxetine (such as decreased libido). However, patients will require close monitoring for signs of the potentially life-threatening condition serotonin syndrome (SS). SS occurs when there is too much serotonin in the central nervous system, and includes symptoms like:

Anyone who suspects they have serotonin syndrome should seek emergency medical attention right away.

Disclaimer: this article does not constitute or replace medical advice. If you have an emergency or a serious medical question, please contact a medical professional or call 911 immediately. To see our full medical disclaimer, visit our Terms of Use page.

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