Key takeaways:
Zoloft (sertraline) and Wellbutrin (bupropion) are two antidepressants. They work differently to help reduce depression symptoms. If needed, it’s possible to safely combine Zoloft and Wellbutrin.
Zoloft and Wellbutrin have different dosages. Most people take Zoloft once a day. People may take Wellbutrin 1 to 4 times daily, depending on their prescribed dosage form.
Zoloft and Wellbutrin have distinct side effects. Zoloft is more likely to cause sexual side effects. And Wellbutrin is more likely to cause trouble sleeping.
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Major depressive disorder (MDD or “depression”) is one of the most common mental health conditions in the U.S. There are several ways to treat depression. Antidepressants are one potential treatment option.
Zoloft (sertraline) and Wellbutrin (bupropion) are two common antidepressants. And while they have some similarities, there are several differences between them. So how do Zoloft and Wellbutrin compare?
Good to know: Brand-name Wellbutrin immediate-release is no longer available in the U.S. It now only comes as a generic medication called bupropion. But for ease of reading, this article uses the word “Wellbutrin” when referring to the medication.
Zoloft vs. Wellbutrin overview
Sometimes, it helps to have information side by side when considering two medications. The table below provides the main differences you need to know when comparing Zoloft versus Wellbutrin.
| Zoloft | Wellbutrin | |
|---|---|---|
| Active ingredient | Sertraline | Bupropion |
| Medication class | Selective serotonin reuptake inhibitor (SSRI) | Norepinephrine and dopamine reuptake inhibitor (NDRI), a type of atypical antidepressant |
| How it works | Helps boost levels of serotonin in the brain | Helps raise levels of norepinephrine and dopamine in the brain |
| Available dosage forms |
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| Approved uses |
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| Approved age ranges |
|
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| Typical dosage |
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| Common side effects |
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Below you’ll find more details about six differences between Zoloft and Wellbutrin.
1. Zoloft and Wellbutrin work differently
One difference between Zoloft and Wellbutrin is that they work differently.
Zoloft is an SSRI. It works by raising levels of serotonin, a chemical messenger in the brain. Serotonin has many functions in the body. One of those actions is helping to regulate mood and anxiety. Raising levels of serotonin is thought to help relieve depression symptoms.
Wellbutrin is not an SSRI. It’s an atypical antidepressant. More specifically, it belongs to a class called norepinephrine and dopamine reuptake inhibitors (NDRIs). Experts aren’t clear on how Wellbutrin works for depression. But they think it helps raise levels of the chemical messengers norepinephrine and dopamine in the brain. Having more of these chemicals available may help improve depression symptoms.
2. Zoloft and Wellbutrin come in different dosage forms
Both Zoloft and Wellbutrin are oral medications that you take by mouth. But they come in different dosage forms.
Zoloft is available as an oral tablet and oral liquid. The liquid provides 20 mg of medication in every 1 mL of liquid. The tablets comes in the following doses:
25 mg
50 mg
100 mg
What antidepressants are available? Zoloft (sertraline) and Wellbutrin (bupropion) are two of several antidepressants used for depression.
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Wellbutrin only comes as an oral tablet. But there are three versions available in the following doses:
Immediate-release (IR): 75 mg and 100 mg
Sustained-release (SR): 100 mg, 150 mg, and 200 mg
Extended-release (ER or XL): 150 mg and 300 mg
Good to know: The active ingredient in Zoloft — sertraline — also comes available as a generic oral capsule. And Wellbutrin’s active ingredient — bupropion — is also sold under the brand names Aplenzin and Forfivo XL. These versions of sertraline and bupropion have different approved uses and come in different doses than brand-name Zoloft and Wellbutrin. They’re not interchangeable.
3. Zoloft and Wellbutrin are FDA-approved for different uses and ages
Another difference between Zoloft and Wellbutrin is what they’re FDA-approved to treat and who’s eligible to take them.
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Zoloft is approved for several mental health conditions:
Depression in adults
Panic disorder in adults
PTSD in adults
Social anxiety disorder in adults
PMDD in adults
OCD in adults and children ages 6 and older
All forms of Wellbutrin are approved to treat depression in adults. But Wellbutrin XL can also be used to treat seasonal affective disorder in adults. This medication isn’t approved for use in children.
Good to know: Certain versions of generic bupropion SR are approved to help adults quit smoking. It used to be sold under the brand name Zyban, which is no longer available. Since Wellbutrin SR contains bupropion SR, it’s common for healthcare professionals to prescribe it for smoking cessation. But this is an off-label use for that specific brand name.
4. Zoloft and Wellbutrin have different typical dosages
The doses for Zoloft and Wellbutrin are different. So be sure to follow the instructions on your prescription bottle carefully.
Zoloft dosage
Most people take Zoloft once a day. The typical starting Zoloft dosage for adults is 50 mg once daily. Children’s doses are based on their age. Starting dosages for children range from 25 mg to 50 mg once daily. The maximum Zoloft dosage for adults and children is 200 mg per day.
If you’re taking the liquid version of Zoloft, it needs to be diluted before you can take it. Mix your prescribed dose with 4 oz of one of the following:
Water
Ginger ale
Lemon-lime soda
Lemonade
Orange juice
Don’t mix liquid Zoloft with any other beverages. After mixing, the liquid may look hazy or cloudy. This is normal. Drink the mixture right away. Don’t save it for a later dose.
Wellbutrin dosage
For Wellbutrin, your dosage depends on what form you’re taking:
Wellbutrin IR: Most people start taking 100 mg by mouth twice daily. After 3 days, your prescriber will likely raise your dose to 100 mg 3 times daily, with at least 6 hours between doses. The maximum Wellbutrin IR dose is 450 mg per day. If you’re taking 400 mg per day or more, it would be split into four smaller doses.
Wellbutrin SR: Most people start with 150 mg by mouth once daily in the morning. After 3 days, your dose will likely be raised to 150 mg twice daily. There should be at least 8 hours between doses. Doses can be raised to a maximum of 400 mg per day (usually taken as 200 mg twice daily).
Wellbutrin XL: Most people start with 150 mg by mouth once a day in the morning. After a few days, this will likely be raised to 300 mg once a day. This is also the maximum recommended dose.
5. Zoloft and Wellbutrin have distinct side effects
Zoloft and Wellbutrin share many common side effects. But there are notable differences between them. The table below lists common side effects for each antidepressant.
| Common Zoloft side effects | Common Wellbutrin side effects |
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The chance of sexual side effects is one notable difference between Zoloft and Wellbutrin. Zoloft commonly causes sexual side effects, including ED and low sex drive. Wellbutrin doesn’t usually cause these issues. In fact, it’s sometimes prescribed to help relieve sexual side effects caused by SSRIs such as Zoloft.
What are the serious side effects of Zoloft and Wellbutrin?
Both Zoloft and Wellbutrin have a boxed warning for suicidal thoughts and behavior. Boxed warnings are the strictest warning that the FDA gives to a medication. In studies, the risk of suicide appears to be higher if you’re under 25 years old. It’s also higher during the first few months of taking Zoloft or Wellbutrin.
Other rare but serious side effects of Zoloft include:
Liver problems
Higher risk of bleeding
Higher risk of seizures
Mania (extreme high energy or excitement) for people living with bipolar disorder
Other rare but serious side effects of Wellbutrin include:
Higher risk of seizures
Severe mental health changes, such as hallucinations or confusion
Mania for people living with bipolar disorder
If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
6. Zoloft and Wellbutrin interact with different medications
Zoloft and Wellbutrin have unique lists of drug interactions, although they also share some interactions.
The table below highlights medications and substances that interact with Zoloft and Wellbutrin. Keep in mind that these aren’t the only possible interactions. Always provide a current medication list to your prescriber and pharmacist.
| Zoloft interactions | Wellbutrin interactions |
|---|---|
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|
Can you take both Zoloft and Wellbutrin?
Yes. In some cases, a prescriber may recommend taking both Zoloft and Wellbutrin. There’s some evidence that this can provide better symptom relief than taking Zoloft by itself. But not everyone needs to take both.
Generally, most people try an SSRI, such as Zoloft, first. If it’s not working well enough, the next step is usually to raise your dosage. But if you’re taking the maximum Zoloft dosage, your prescriber may suggest switching to a different antidepressant or adding an atypical antidepressant, such as Wellbutrin.
Healthcare professionals may also recommend adding Wellbutrin if Zoloft is causing certain side effects. As mentioned, Wellbutrin can help combat the sexual problems that SSRIs cause.
How to save on Zoloft and Wellbutrin
Zoloft, Wellbutrin SR, and Wellbutrin XL are available as brand-name medications. You can also find all versions of Zoloft and Wellbutrin as lower-cost generics. GoodRx can help you navigate ways to save on your prescription.
Zoloft: Generic sertraline at certain pharmacies costs as little as $9.55 with a free GoodRx coupon. If you have commercial insurance, brand-name Zoloft could be as little as $4 per month using a copay savings card from the manufacturer.
Wellbutrin IR: This form of Wellbutrin is only available as a generic medication. Generic bupropion’s price at certain pharmacies is as low as $8.37 with a free GoodRx discount.
Wellbutrin SR: Generic bupropion SR at certain pharmacies costs as little as $11.40 with a free GoodRx coupon.
Wellbutrin XL: Generic bupropion XL may be as low as $7.29 with a free GoodRx coupon. If you have commercial insurance, you can get brand-name Wellbutrin XL for as little as $0 per prescription with a manufacturer copay card.
Frequently asked questions
Zoloft is more likely to cause weight gain than Wellbutrin. But weight gain with Zoloft is usually minor. And it’s more likely to happen if you’re taking it for more than 6 months. Wellbutrin can cause weight loss for some people who take it. It’s very unlikely to lead to weight gain.
It’s possible that you may have more energy while taking Wellbutrin. But it’s more likely that this effect is because Wellbutrin is lessening your depression symptoms — not a direct effect of the medication. Keep in mind that Wellbutrin can cause trouble sleeping and agitation. These side effects could make you feel like you have too much energy or are restless.
Wellbutrin isn’t a first-choice treatment for anxiety. SSRIs, such as Zoloft, are more commonly prescribed to manage anxiety disorders. But there is some evidence that Wellbutrin could be beneficial for people living with both anxiety and depression.
There’s also an anxiety medication called buspirone. Its name is very similar to Wellbutrin’s generic name (bupropion). Many people mix the two names up.
Zoloft is more likely to cause weight gain than Wellbutrin. But weight gain with Zoloft is usually minor. And it’s more likely to happen if you’re taking it for more than 6 months. Wellbutrin can cause weight loss for some people who take it. It’s very unlikely to lead to weight gain.
It’s possible that you may have more energy while taking Wellbutrin. But it’s more likely that this effect is because Wellbutrin is lessening your depression symptoms — not a direct effect of the medication. Keep in mind that Wellbutrin can cause trouble sleeping and agitation. These side effects could make you feel like you have too much energy or are restless.
Wellbutrin isn’t a first-choice treatment for anxiety. SSRIs, such as Zoloft, are more commonly prescribed to manage anxiety disorders. But there is some evidence that Wellbutrin could be beneficial for people living with both anxiety and depression.
There’s also an anxiety medication called buspirone. Its name is very similar to Wellbutrin’s generic name (bupropion). Many people mix the two names up.
The bottom line
Zoloft (sertraline) and Wellbutrin (bupropion) are effective options for treating depression. They work differently and have different dosages. Zoloft is a once-daily medication. People take Wellbutrin 1 to 4 times daily, depending on their dosage form.
Zoloft and Wellbutrin also have distinct side effects. Zoloft has a tendency to cause more sexual side effects than Wellbutrin. But Wellbutrin may be more likely to cause trouble sleeping. If needed, it’s possible to safely take Zoloft and Wellbutrin together.
If you’re experiencing symptoms of depression, discuss your options with your healthcare team. Together, you can decide which medication might work better for you.
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References
Almatica Pharma. (2023). Sertraline HCL- sertraline hydrochloride capsule [package insert].
American Psychiatric Association. (2010). Practice guideline for the treatment of patients with major depressive disorder.
Bausch Health. (2024). Wellbutrin XL- bupropion hydrochloride tablet, extended release [package insert]. DailyMed.
Bryant Ranch Prepack. (2025). Bupropion hydrochloride- bupropion hydrochloride tablet, film coated [package insert].
Dr. Reddy's Laboratories. (2024). Bupropion hydrochloride (SR)- bupropion hydrochloride tablet, extended release [package insert]. DailyMed.
Endocrine Society. (2022). Adrenal hormones.
Glaucoma Research Foundation. (n.d.). Angle-closure glaucoma.
GlaxoSmithKline. (2024). Wellbutrin SR- bupropion hydrochloride tablet, film coated [package insert]. DailyMed.
Huecker, M. R., et al. (2024). Bupropion. StatPearls.
Poliacoff, Z., et al. (2023). Does bupropion increase anxiety? Journal of Clinical Psychopharmacology.
Roerig. (2023). Zoloft- sertraline hydrochloride tablet, film coated [package insert]. DailyMed.
TWi Pharmaceuticals. (2024). Forfivo XL- bupropion hydrochloride tablet, film coated, extended release [package insert].
