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Wellbutrin vs. Prozac: Differences, similarities, and which one is better for you

Wellbutrin and Prozac are prescription medications that treat depression

Main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Wellbutrin (bupropion) and Prozac (fluoxetine) are medications that can treat depression. Specifically, these drugs are prescribed to treat major depressive disorder. Symptoms of major depressive disorder may include feelings of sadness or hopelessness, loss of interest in daily activities, and problems with sleep. 

Wellbutrin and Prozac are only available with a prescription from a doctor or healthcare provider. Although they have similar uses, Wellbutrin and Prozac work in different ways and have different side effects. Continue reading to learn more about the similarities and differences between Wellbutrin and Prozac. 

What are the main differences between Wellbutrin and Prozac?

Wellbutrin is an aminoketone antidepressant that is also known by its generic name, bupropion. The exact way in which Wellbutrin works is not well understood. However, it is believed to increase levels of certain neurotransmitters called norepinephrine and dopamine in the brain. Individuals with depression may have an imbalance of these neurotransmitters. Unlike other commonly prescribed antidepressants, Wellbutrin has no effect on serotonin levels. 

Wellbutrin is available in three different formulations: immediate-release (IR), sustained-release (SR), and extended-release (XL). Depending on the dosage form, Wellbutrin can be taken once, twice, or three times daily. The active ingredient in Wellbutrin, bupropion, is also marketed as Zyban to support smoking cessation. 

Prozac is one of the most commonly prescribed antidepressants. It is also known by the generic name fluoxetine. Prozac belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs). These drugs work by increasing levels of the neurotransmitter serotonin to ease symptoms of depression. 

Prozac comes as a daily oral capsule. The exact dosage depends on the condition being treated. Prozac is also available as a delayed-release capsule that is taken once per week.

Differences between Wellbutrin and Prozac
Wellbutrin Prozac
Drug class Aminoketone  Selective serotonin reuptake inhibitor
Brand/generic status Brand and generic available Brand and generic available
What is the generic name? Bupropion Fluoxetine
What form(s) does the drug come in? Oral tablet Oral capsule, Delayed-release
What is the standard dosage? 100 mg three times daily
Dosage dependent on condition
20 mg once per day
Dosage dependent on condition
How long is the typical treatment? Long term depending on the condition being treated Long term depending on the condition being treated
Who typically uses the medication? Adults Adults; children 8 years and older (depression)

Conditions treated by Wellbutrin and Prozac

All forms of Wellbutrin are approved by the Food and Drug Administration (FDA) to treat major depressive disorder, also known as major depression. Wellbutrin XL, the extended-release form of Wellbutrin, is also approved to prevent seasonal affective disorder (SAD), a type of depression that develops during seasonal changes. Wellbutrin is sometimes used off-label to treat bipolar disorder

Prozac is FDA approved to treat major depressive disorder. It is also approved to treat obsessive-compulsive disorder (OCD) and panic disorder, as well as an eating disorder called bulimia nervosa. When used along with an antipsychotic called Zyprexa (olanzapine), Prozac is used to treat depressive episodes in those with bipolar disorder. Some individuals with depression may not respond to other medications and thus, they may be prescribed Prozac and Zyprexa (olanzapine). Prozac is marketed under a different brand name called Sarafem to treat premenstrual dysphoric disorder

Wellbutrin and Prozac have also been studied for the treatment of ADHD. One study found that Wellbutrin helped improve symptoms of ADHD compared to placebo.

Condition Wellbutrin Prozac
Major depression Yes Yes
Depression associated with seasonal affective disorder Yes Off-label
Depression associated with bipolar I disorder Off-label Yes
Obsessive-compulsive disorder (OCD) No Yes
Panic disorder No Yes
Bulimia nervosa No Yes
Premenstrual dysphoric disorder (PMDD) No Yes
Attention-deficit hyperactivity disorder (ADHD) Off-label Off-label

Is Wellbutrin or Prozac more effective?

Wellbutrin and Prozac are effective prescription medications for treating depression. The best antidepressant will depend on a number of factors such as cost, individual response to treatment, and potential side effects. Consult a healthcare provider on the best treatment options for your condition. 

According to one double-blind comparison study, bupropion and fluoxetine were found to be similar in effectiveness for the treatment of depression. The study was conducted over seven weeks and utilized the Hamilton Rating Scale for Depression among other tools to assess treatment efficacy. Both bupropion and fluoxetine helped relieve depression symptoms with no severe adverse effects. 

One systematic review found that Wellbutrin is an effective and safe medication compared to other antidepressants. Wellbutrin may have less side effects compared to SSRIs. It also causes less sexual side effects and weight gain than other antidepressants. 

A systematic review found that Prozac is an effective medication for several mental health conditions, including depression, bulimia, and OCD. Prozac was found to be more effective than placebo in some studies within the review. It was also found to be as effective as Anafranil (clomipramine) for treating OCD.

Coverage and cost comparison of Wellbutrin vs. Prozac

The average cost of Wellbutrin XL without insurance is around $194. Wellbutrin XL is available in a generic form that is usually covered by most Medicare and health insurance plans. With a SingleCare prescription discount card, you may be able to lower the cost of the generic Wellbutrin XL to around $5, depending on the dosage and quantity prescribed. 

Prozac is available in a generic form. It is usually covered by most insurance plans. The average cash price of Prozac is around $300. However, the price can vary depending on the dosage and quantity prescribed. A SingleCare prescription discount card for generic Prozac is available, which can help lower the cost to $4. 

Wellbutrin Prozac
Typically covered by insurance? Yes Yes
Typically covered by Medicare Part D? Yes Yes
Quantity 30 tablets 30 capsules
Typical Medicare copay $0–$2 $12
SingleCare cost $5 $4–$20

Common side effects of Wellbutrin vs. Prozac

The most common side effects of Wellbutrin are dry mouth, nausea, dizziness, insomnia, stomach upset, anxiety, palpitations, and sweating. Wellbutrin may also cause muscle aches, rash, and itching. Weight changes have also been reported while using Wellbutrin. However, Wellbutrin is more likely to cause weight loss than weight gain. 

The most common side effects or Prozac include sexual dysfunction, decreased sex drive, diarrhea, indigestion, nausea, fatigue, dizziness, and drowsiness. Prozac may also cause rash, flu-like symptoms, and tremors. Weight changes have also been reported with Prozac. 

Severe side effects of Wellbutrin and Prozac include worsened depression and suicidal thoughts or behaviors. Seek immediate medical attention if you experience worsened depression symptoms. You should also seek medical attention if you experience an allergic reaction to Wellbutrin or Prozac. Symptoms of an allergic reaction include hives, trouble breathing, or swelling of the face or throat. 

Wellbutrin Prozac
Side effect Applicable? Frequency Applicable? Frequency
Nausea Yes 13% Yes 22%
Indigestion Yes 3% Yes 8%
Dry Mouth Yes 17% Yes 9%
Constipation Yes 10% Yes 5%
Diarrhea Yes 5% Yes 11%
Muscle pain Yes 2% No
Anxiety Yes 5% Yes 12%
Rash Yes 5% Yes 4%
Dizziness Yes 7% Yes 9%
Somnolence Yes 2% Yes 12%
Tremor Yes 6% Yes 9%
Insomnia Yes 11% Yes 19%
Decreased libido No Yes 4%
Palpitations Yes 2% Yes 1%

Source: DailyMed (Wellbutrin SR), DailyMed (Prozac)

Drug interactions of Wellbutrin vs. Prozac

Wellbutrin should not be combined with a monoamine oxidase inhibitor (MAOI), such as selegiline or phenelzine. Taking Wellbutrin with an MAOI can increase the risk of high blood pressure. Prozac should also be avoided with an MAOI. Combining Prozac with an MAOI can increase the risk of serotonin syndrome, a condition that may require hospitalization. Wellbutrin or Prozac should also not be taken within 14 days of stopping an MAOI. 

Dopaminergic drugs like levodopa and amantadine can interact with Wellbutrin. Using these medications with Wellbutrin can increase the risk of adverse effects, such as restlessness, dizziness, and tremors. 

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) or warfarin should be avoided or monitored while taking Prozac. This drug interaction may lead to an increased risk of bleeding.

Prozac can also interact with other serotonergic drugs like certain opioids, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), seizure medications, and mood stabilizers. Taking these medications with Prozac may increase the risk of serotonin syndrome. 

Drug Drug class Wellbutrin Prozac
Selegiline
Rasagiline
Isocarboxazid
Phenelzine
MAOIs Yes Yes
Levodopa
Amantadine
Dopaminergic  Yes No
Pimozide
Thioridazine
Antipsychotic Yes Yes
Fentanyl 
Tramadol
Opioids Yes Yes
Amitriptyline
Nortriptyline
Imipramine
Desipramine
Tricyclic antidepressant Yes Yes
Venlafaxine
Desvenlafaxine
Duloxetine
SNRIs Yes Yes
St. John’s Wort Herbal Yes Yes
Phenytoin
Fosphenytoin
Antiepileptic Yes Yes
Lithium Mood stabilizer Yes Yes
Ibuprofen
Naproxen
Aspirin
NSAIDs No Yes
Warfarin Anticoagulant No Yes

*Consult a healthcare professional for other drug interactions

Warnings of Wellbutrin and Prozac

Both drug labels for Wellbutrin and Prozac contain black box warnings about suicidal thoughts and behaviors. There may be an increased risk of worsened depression while taking Wellbutrin or Prozac. Seek immediate medical attention if your symptoms don’t improve or you experience suicidal thoughts and behaviors. 

There may be an increased risk of seizures while taking Wellbutrin, especially in higher doses. The use of Wellbutrin is also associated with an increased risk of high blood pressure, mania, psychosis, and glaucoma in certain people. Consult a healthcare provider if you have had a history of these conditions before taking Wellbutrin. 

Like Wellbutrin, Prozac also carries a risk of seizures, mania, and glaucoma. In addition, the use of Prozac can also increase the risk of serotonin syndrome. Signs and symptoms of serotonin syndrome include confusion, rapid heart rate, and muscle stiffness, among others. Low sodium levels (hyponatremia), heart rhythm problems (QT prolongation), and abnormal bleeding have also been reported with Prozac in certain people. 

Seek medical advice from a healthcare provider prior to starting treatment with Wellbutrin or Prozac. 

Frequently asked questions about Wellbutrin vs. Prozac

What is Wellbutrin?

Wellbutrin is an aminoketone antidepressant that is FDA approved to treat major depressive disorder. It comes in an immediate-release, sustained-release, and extended-release form. In addition to treating major depressive disorder, Wellbutrin XL is also approved to prevent seasonal affective disorder. The generic name of Wellbutrin is bupropion. 

What is Prozac?

Prozac is a selective serotonin reuptake inhibitor (SSRI) that is FDA approved to treat major depressive disorder. As an SSRI antidepressant, Prozac can also treat depression associated with bipolar disorder. Prozac is also approved to treat other mental health conditions, including OCD, panic disorder, bulimia, and premenstrual dysphoric disorder (as Sarafem). Prozac comes in a daily or weekly oral capsule. The generic name of Prozac is fluoxetine

Are Wellbutrin and Prozac the same?

Both Wellbutrin and Prozac are antidepressant medications but they work in different ways. Wellbutrin is an aminoketone that works by increasing the levels of norepinephrine and dopamine in the brain. Prozac is an SSRI that works by increasing the levels of serotonin in the brain. A doctor who specializes in psychiatry may prescribe these prescription drugs to treat various mental health conditions, primarily depression. 

Is Wellbutrin or Prozac better?

Wellbutrin and Prozac are similarly effective for treating depression. The best antidepressant is the one that causes the least side effects and is more cost effective, depending on the situation. Wellbutrin causes less sexual side effects and weight gain than SSRIs like Prozac. Other SSRIs include Paxil (paroxetine), Zoloft (sertraline), Lexapro (escitalopram), and Celexa (citalopram). Prozac may be more appropriate than Wellbutrin to treat depression in an individual with bipolar disorder, bulimia, or OCD. Antidepressant medications often work better in combination with psychotherapy. 

Can I use Wellbutrin or Prozac while pregnant?

Wellbutrin may be prescribed to treat depression during pregnancy. However, there may be a risk of birth defects and miscarriage while using Wellbutrin during pregnancy. Prozac is not recommended during late pregnancy due to the risk of pulmonary hypertension, respiratory distress, and other problems in the infant. Wellbutrin and Prozac may pass into the breast milk. Consult a healthcare provider before taking an antidepressant while pregnant or breastfeeding. 

Can I use Wellbutrin or Prozac with alcohol?

It is not generally recommended to drink alcohol while taking Wellbutrin or Prozac. Combining alcohol with antidepressants can increase the risk of side effects such as drowsiness and dizziness. Therefore, alcohol consumption should be monitored or minimized while taking Wellbutrin or Prozac.