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Wellbutrin vs Zoloft: Differences & Similarities

Vicky Davis

Medically reviewed by Vicky Davis, FNP

Written by Our Editorial Team

Last updated 6/14/2021

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

Likewise, the field of medication available can feel a little overwhelming, with hard-to-pronounce names and lengthy lists of side effects making the whole process of choosing one intimidating. 

One of the most frequently compared pairs of medication are Wellbutrin® and Zoloft®, which are both antidepressants, but have very different mechanisms of effect on 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. 

We’re going to address the differences and similarities of these two medications, but first we should address some basics about depression.

Depression Quick Facts

The National Institute of Mental Health (NIMH) defines depression as a mood disorder characterized by ongoing patterns of sad, empty and down feelings that affect day-to-day activity. 

There are several types of depression, including Seasonal Affective Disorder (SAD), which occurs in cold, dreary winter months. 

By comparison, major depression is an intense period of depression that affects all aspects of a person’s life for a period of at least two weeks (but often significantly longer).

Long term depression (called persistent depressive disorder) can last two years or much longer. 

Depression can be the result of various biological, genetic, psychological and environmental factors, though we don’t know as much as we could about the root causes. 

Mood issues like anger, exhaustion or irritability are common symptoms of depressed people, as are tendencies to behave recklessly, abuse substances and to lose interest in things they like. 

Sufferers can even have suicidal thoughts. 

It’s a condition that can be miserable, taxing and create hopelessness for the sufferer — which is why you’d want treatments like Zoloft or Wellbutrin. These two are different and yet similar medications. 

Let’s look at them in detail.

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What is Zoloft?

Zoloft is the brand-name version of an antidepressant called sertraline, which is a selective serotonin reuptake inhibitor (SSRI). 

It was approved in the early ‘90s to regulate mood and personality, and has additional effects on dopamine and norepinephrine. 

It’s traditionally presented as an oral tablet, but can be prescribed in a liquid form, as well.  

The Food and Drug Administration (FDA) approved Zoloft to treat several conditions, including major depressive disorder, OCD, panic disorder, PTSD, premenstrual dysphoric disorder and social anxiety. 

But Zoloft also has off-label uses. It can be prescribed to treat binge eating disorders, body dysmorphic disorders, forms of bulimia, generalized anxiety disorder and even premature ejaculation. 

Zoloft side effects include nausea, vomiting, diarrhea, constipation, difficulty falling asleep, dry mouth, heartburn, weight changes, headache, nervousness, change in sex drive, excess sweating and uncontrollable shaking of a part of the body.

Serious side effects include seizures, rash, weakness, confusion, swelling, difficulty breathing, abnormal bleeding or bruising, agitation, hallucinations. 

Any of these symptoms should be immediately brought to the attention of a healthcare professional.

What Is Wellbutrin?

Similar to Zoloft, Wellbutrin is a brand name version of an antidepressant. It’s generic name is bupropion and it was approved in 1985 by the FDA. 

Bupropion is a particular type of dopamine-targeting medication called a norepinephrine and dopamine reuptake inhibitor (NDRI), which prevents dopamine and norepinephrine from being reabsorbed, leaving a larger supply of both available in the brain for proper function.

Typically, it will take at least two weeks to feel the effects once you start taking this medication. It’s available in two forms, both oral tablets, which work either as 12 or 24 hour extended release pills.

Wellbutrin is FDA approved for depression, seasonal affective disorder and smoking cessation, but it has off-label uses to treat antidepressant-induced sexual dysfunction, ADHD, bipolar-related depression and obesity.

Side effects of Wellbutrin and bupropion include a fairly long list of mild issues, including dry mouth, nausea, headache, vomiting, stomach pain, anxiety, drowsiness, loss of appetite, weight loss, constipation, excessive sweating, ringing in the ears, sore throat, uncontrollable shaking of body parts, frequent urination and changes to your sense of taste. 

Serious side effects include seizures, confusion, hallucination, irrational fears, muscle or joint pain and rapid heart beat. 

All of these should be brought to the attention of a healthcare provider immediately if they’re noticed. 

Likewise, you should contact a healthcare professional if you experience hives, hoarseness, itching, rash, fever, blisters, swelling or difficulty swallowing or breathing.

The Differences Between Wellbutrin and Zoloft

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.  

Zoloft has more dopamine and norepinephrine targeting ability than other SSRIs, but it’s not comparable to Wellbutrin. 

The second difference: how you take it. 

Zoloft is typically prescribed to be taken once a day, 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.

With those points out of the way, there are larger issues to worry about, particularly if you are sexually active. 

One of the key differences between the two, however, is their effects on sexual function. 

One study found that, all things aside, Wellbutrin is better for patients who are sexually active, because it has significantly lower instances of interfering with sexual function, 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. 

Their side effects, for the most part, are pretty similar. 

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.

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Which One Is Better For You?

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 2006 study found that both medications were found to be effective in treating depression for people who didn’t get what they needed out of other traditional SSRIs.

Who can tell you which one is right for you? Not us. 

A healthcare professional will both recommend and prescribe the right medication 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. 

For conditions like depression, holistic treatment might mean exercise and diet changes, losing weight and seeking therapy, and if that’s the case, a healthcare professional will be able to recommend or refer you to someone who might help. 

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.

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.

8 Sources

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.

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  5. U.S. National Library of Medicine. (n.d.). Bupropion: MedlinePlus Drug Information. MedlinePlus.
  6. Croft, H., Settle, E., Jr, Houser, T., Batey, S. R., Donahue, R. M., & Ascher, J. A. (1999). A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clinical therapeutics, 21(4), 643–658.
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  8. Depression Basics. (n.d.). Retrieved January 08, 2021, from

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.

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