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Wellbutrin vs Zoloft: Differences & Similarities

Kristin Hall, FNP

Reviewed by Kristin Hall, FNP

Written by Geoffrey Whittaker

Published 06/13/2021

Updated 03/10/2022

There are a lot of ways to fight depression. From therapy and meditation to pills and exercise, the options are endless. 

One of the most frequently compared pairs of medication are Wellbutrin® (bupropion) and Zoloft® (sertraline), which are both antidepressant medications but have very different mechanisms of effect on major depression

You might be here right now because a healthcare professional has offered you one or both — in the past or recently — and you’re trying to understand the difference. 

You might also be here because you’ve tried one of these in the past, and now you’re wondering why the other is supposed to be different.

In depression treatment, trying more than one medication to find the right fit is like trying on shoes when you’re young — it’s necessary because things change. 

Your needs may be different, and the right “fit” may mean something different. 

Let's address the differences and similarities of these two medications.

To start off, the biggest similarity here is that both Wellbutrin and Zoloft are FDA approved for the treatment of depression. But what other similarities do these drugs have?

Side Effects

For the most part, the side effects of Zoloft and Wellbutrin are pretty similar. Dry mouth, constipation, headaches, insomnia and nausea are shared side effects between the two. 

One concern might be that one would have a more significant impact on anxiety, but despite side effect warnings, differences are considered clinically insignificant between the two with regards to their effects on anxiety, according to an article published in The Journal of Clinical Psychiatry.

Read more about sertraline side effects and bupropion side effects.

Even though Wellbutrin and Zoloft may seem similar at first glance, there are many small differences that make these two drugs stand apart from each other, and could make a difference for you in your depression treatment. 

What do they Target?

As you may have already noticed, the main difference between Wellbutrin and Zoloft is what the medication targets. 

Wellbutrin acts primarily on dopamine and norepinephrine, and while Zoloft can also have minimal effects on both, it’s not primarily designed for those purposes.  

Learn more about SSRIs here.

What do they Treat?

It's true that both brand name Zoloft and Wellbutrin treat major depressive disorder, but each drug holds separate FDA and off-label uses that set them apart.

Zoloft is approved by the Food and Drug Administration to treat social anxiety disorder, post-traumatic stress disorder and obsessive-compulsive disorder (OCD). It is also often prescribed off-label by healthcare providers to treat generalized anxiety disorder and separation anxiety disorder.

Additionally, healthcare providers sometimes prescribe Wellbutrin as a treatment for ADHD, according to a review published in the Cochrane Database of Systematic Reviews.

Learn more: Does Wellbutrin Help with Anxiety?

How to Take Zoloft vs Wellbutrin 

Zoloft is typically prescribed to be taken once a day to treat major depressive disorder and can be taken in a liquid form. Wellbutrin is only available as tablets but can be taken in either daily or twice-daily formats.

Sexual Side Effects

One of the key differences between the two meds, however, is their effects on sexual function, according to an article published in the journal, Clinical Therapeutics. 

One study found that, all things aside, Wellbutrin is better for patients who are sexually active, because it has significantly lower instances of sexual dysfunction or problems with ejaculation, which is a common side effect with SSRIs.

But generally speaking, these two medications are both considered safe, effective and treat many of the same issues and concerns arising from the same conditions and disorders. 

Actually, yes. You can take Wellbutrin and Zoloft together. According to an article published in the Journal of Psychopharmacology, about 15-20% of depression patients experience depressive symptoms that are persistent beyond appropriate treatment. This is where doubling up on Wellbutrin and Zoloft comes in. 

Because each drug targets a different part of the brain, the study says that there was efficacy in combining both drugs. 

None of the participants of this study experienced adverse effects from the combination, but combining these drugs may increase your risk of seizures and heightened adverse effects. It is important to seek medical advice about drug interactions from your healthcare provider before taking sertraline and bupropion at the same time. 

Depression and anxiety disorders aren’t one-size-fits-all issues — they can be hyper-individualized and can happen simultaneously. 

The good news on both of these pills is that they can be a refuge for depression sufferers who haven’t had luck with other medications. 

A healthcare professional will both recommend and prescribe the right treatment option for you. 

They’ll also address other potential factors in your depression battle — things like lifestyle and recent or previous stressors and traumas — that might be causing you distress. 

If you’re just learning about depression, we have other resources you might want to examine, including our guide to the types of therapy and our mental health resources guide.

We also cover the differences between Wellbutrin and Prozac, another common antidepressant.

Keep reading, but do yourself a favor and take the next step, too — talk to someone. Get the help you do deserve for a problem you don’t deserve. Schedule an online psychiatry evaluation today.

You’ll thank yourself.

6 Sources

  1. Ascher, et al. (n.d.). A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clinical therapeutics. Retrieved February 15, 2022, from
  2. Bekkering, et al. (2017, October 2). Bupropion for attention deficit hyperactivity disorder (ADHD) in adults. The Cochrane database of systematic reviews. Retrieved February 15, 2022, from
  3. Collins, et al. (n.d.). Bupropion and sertraline combination treatment in refractory depression. Journal of psychopharmacology (Oxford, England). Retrieved February 15, 2022, from
  4. Prescribing information Wellbutrin - Food and drug ... (n.d.). Retrieved February 15, 2022, from
  5. Reference ID: 4032692 - food and drug administration. (n.d.). Retrieved February 15, 2022, from
  6. Trivedi MH;Rush AJ;Carmody TJ;Donahue RM;Bolden-Watson C;Houser TL;Metz A; (n.d.). Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? The Journal of clinical psychiatry. Retrieved February 15, 2022, from
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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.

Kristin Hall, FNP

Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership. 

She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH

Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare. 

Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.

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