Wellbutrin vs Zoloft: Which is Right for Me?

By Arielle Mitton
Medically reviewed checkmarkMedically reviewed
March 23, 2022

There are many ways to treat depression.

Therapy, lifestyle changes, and medication are all options that can help and may be recommended by your doctor. 

You might be here right now because a healthcare professional has suggested taking an antidepressant drug like Wellbutrin or Zoloft.

Or, maybe you’ve heard of these medications and want to understand the differences between them.

Wellbutrin and Zoloft are two very common prescription medications used to treat mental illnesses like major depressive disorder (MDD), seasonal affective disorder, and anxiety disorders.

In this article, I’ll go over how Wellbutrin and Zoloft work, key differences between these medications, and precautions you should bear in mind. 

What is Wellbutrin?

Wellbutrin is the brand name prescription drug of bupropion.

There are three types of Wellbutrin medications available for patients: Wellbutrin, Wellbutrin SR, and Wellbutrin XL.

Wellbutrin is an immediate release drug, Wellbutrin SR is a sustained release drug, and Wellbutrin XL is an extended release drug.

They all have the same active ingredient (bupropion hydrochloride), but Wellbutrin XL releases more slowly in the body. 

Since Wellbutrin XL is released at a slower rate of up to 24 hours, it means a steady amount of the medication will remain in your system during the day.

It also means that the active ingredient remains in your system for a longer amount of time.

Most people who take Wellbutrin XL will take one dose a day. 

On the other hand, Wellbutrin is released immediately and absorbed the fastest.

Patients may take 2-3 pills of Wellbutrin daily, depending on their doctor’s prescription instructions.

Wellbutrin SR is absorbed in the body faster than the XL formulation and releases medication for up to 12 hours.

In most cases, Wellbutrin SR is taken twice a day.

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Wellbutrin uses

Wellbutrin is an antidepressant medication used to treat a variety of mental illnesses, including:

In some (less common) cases, Wellbutrin may also be prescribed to help treat bipolar disorder, social anxiety disorder, and post-traumatic stress disorder.  

Additionally, the active ingredient of Wellbutrin, bupropion hydrochloride, is the active ingredient in another drug called Zyban, which is used to help people quit smoking. 

How Wellbutrin works

Wellbutrin medications act as a norepinephrine-dopamine reuptake inhibitors (NDRI) and chemically fall under the aminoketone class .

NDRIs work by preventing dopamine (a neurotransmitter that plays a key role in how we feel pleasure) and norepinephrine (a neurotransmitter that increases alertness and reaction time) from being reabsorbed, leaving a large supply of both available in the brain. 

Studies indicate that boosting norepinephrine and dopamine can help treat the symptoms of depression.

What is Zoloft?

Zoloft is a brand name version of the antidepressant drug sertraline.

Sertaline belongs to a class of medications called selective serotonin reuptake inhibitors (SSRI). 

It is available as tablets in doses of 25 mg, 50 mg, and 100 mg, and is also available in liquid form with a concentration of 20 mg/mL.

Zoloft uses

Zoloft is an antidepressant medication that is approved for the treatment of:

  • Major depressive disorder (MDD)
  • Posttraumatic stress disorder (PTSD)
  • Premenstrual dysphoric disorder (PMDD)
  • Panic disorder
  • Social anxiety disorder

In some cases, Zoloft may also be prescribed to treat obsessive compulsive disorder (OCD) in children 6-17 years of age and in adults.

How Zoloft works

Low levels of serotonin are linked to symptoms like depressed mood, fatigue, and difficulty sleeping.

Serotonin is a neurotransmitter that acts like a mood stabilizer.

It’s also responsible for helping regulate digestion and sleep.

Many people know serotonin as the “happiness hormone.”

SSRIs like Zoloft work by increasing the level of available serotonin in the brain.

Zoloft blocks the reabsorption of serotonin in the brain, leaving more of it readily available.

This may help improve mood, sleep patterns, and appetite, while decreasing compulsive behaviors, feelings of anxiety, and panic attacks.

How are They Similar?

Wellbutrin and Zoloft are both antidepressant medications that require a prescription from a medical doctor.

They are both commonly prescribed to help manage depressive disorders, but that really is where the similarities end. 

These two drugs contain different active ingredients that achieve different things, and they should not be used interchangeably. 

How are They Different?

The main difference between Wellbutrin and Zoloft is in their active ingredients. 

Wellbutrin’s active ingredient is bupropion, which is an NDRI that attempts to increase levels of dopamine and norepinephrine in the brain.

Zoloft’s active ingredient is sertraline, which is an SSRI that works to increase levels of available serotonin. 

Conditions treated

Although both Zoloft and Wellbutrin are prescribed to treat common mental health conditions, the different way these two prescription medications work means they are each better suited for particular conditions. 

Wellbutrin is primarily used as a treatment for patients with depressive symptoms, while Zoloft can help treat both depression and anxiety disorders.

Drug class

Wellbutrin falls under the NDRI drug class and Zoloft falls under the SSRI drug class.

Both prescription drugs are FDA-approved and available by prescription only. 

Side effects

Like many other medications, antidepressants come with their own set of risks and side effects.

Before you begin taking Wellbutrin or Zoloft, discuss potential side effects with your doctor.

Many patients will experience mild side effects that subside after several days.

If you experience severe side effects or begin to have suicidal thoughts after taking Wellbutrin or Zoloft, seek immediate medical care. 

Wellbutrin and Zoloft are safe, FDA-approved drugs, but they also come with an FDA black box warning that states, “all patients being treated with antidepressants for any indication should watch for and notify their healthcare provider for worsening symptoms, suicidality and unusual changes in behavior, especially during the first few months of treatment.”

Wellbutrin Precautions

Before you begin taking Wellbutrin, it’s a good idea to talk to your doctor about potential side effects and risk factors.

Some of the most common side effects of Wellbutrin that people may experience include:

Generally, these side effects will begin going away after a week or two.

If they persist or are severe, make sure to let your doctor know.

Also, Wellbutrin is a medication that has a black box warning—the strongest type of warning assigned by the FDA.

The warning is for suicidal thoughts and behaviors, and children, adolescents, and adults under the age of 25 are all at greater risk of developing.

If you take Wellbutrin and experience sudden mood changes, a manic episode, severe confusion, or begin having thoughts about self-harm, seek immediate medical attention.

In addition, there are a few other rare side effects to be aware of, such as having an allergic reaction.

If you experience hives, itching, swollen glands, or difficulty breathing, get immediate medical help and notify your physician.

Below are a couple of other rare side effects, along with the groups of people that may be at greater risk.

  • Seizures: If you have a history of seizures, a previous head injury, brain tumor, or severe liver disease, the risk of having a seizure while taking Wellbutrin increases. Other risk factors include having an alcohol or drug dependence, taking other certain prescription medications, or taking higher than recommended doses of Wellbutrin. Before you begin taking Wellbutrin, your doctor should be informed if you have any of these risk factors, and of the current medications you are taking.
  • Adverse cardiovascular effects: Although the risk of adverse cardiovascular effects is low, this risk increases if you are diagnosed with heart disease, high blood pressure, or irregular heartbeat, or if you’ve had a heart attack in the past. If you fall under one of these risk factors, make sure to communicate your medical history and any concerns with your doctor. Depending on your case, your doctor may require a cardiovascular evaluation before starting Wellbutrin. 

Zoloft Precautions

If you’ve been prescribed Zoloft, you should talk about common side effects with your doctor and feel free to bring up any questions or concerns you may have.

Having an open, communicative relationship with your doctor will be key to successful management of mental illness.

Below are common Zoloft side effects:

  • Headache
  • Nausea
  • Diarrhea
  • Dry mouth
  • Increased sweating
  • Feeling nervous or restless
  • Fatigue
  • Difficulty sleeping (insomnia)

These side effects should subside as you continue the course of treatment.

If these side effects do not go away, are severe, or worsen over time, let your doctor know.

There are also a few serious side effects that, while rare, are important to be aware of. 

  • Low sodium blood levels: Decreased sodium in your blood can cause symptoms like headache, weakness, confusion, and difficulty concentrating or remembering. The risk of low sodium increases when zoloft is used with other medications, so be sure to tell your doctor about any other medications you use on a regular basis.
  • Serotonin syndrome: You may think that you could never have too much serotonin, but too much of anything can be harmful. Serotonin syndrome is a rare and potentially life-threatening condition where there’s too much serotonin in the brain. Typical symptoms include increased heart rate, sweating, muscle stiffness or spasms, fever, and confusion. If you are using any other medications that affect serotonin levels, you may be at higher risk of developing this serious syndrome. If these symptoms happen to you while taking Zoloft, talk to your doctor immediately or call 911 to get to the nearest ER.
  • Higher bleeding risk: Zoloft can increase risk of bleeding or bruising, especially if you are taking any blood-thinning drugs like aspirin or NSAIDs (like Advil). If you notice symptoms like black stool, blood in urine, or unusual bleeding or bruising, contact your doctor immediately. 

Remember, Zoloft also comes with an FDA black box warning that says you should monitor and notify your doctor of any severe symptoms, thoughts of suicide, or unusal changes in behavior. 

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When to See a Doctor for Depression

If you are struggling with symptoms of mental illness, you are not alone.

According to the National Alliance on Mental Illness, 21% of adults in the United States experienced mental illness in 2020.

Mental health is just as important as physical health, and if you do not feel well, there is help out there for you. 

It’s recommended that you seek help from a healthcare professional if you are experiencing any of the following symptoms:

  • You’re no longer interested in most activities or beloved hobbies
  • You have feelings of sadness, emptiness, or hopelessness most of the time
  • You have trouble falling asleep, staying asleep, or you regularly oversleep
  • You have little to no energy most of the time
  • You are eating more or less than usual
  • You are easily irritable
  • You have difficulty concentrating or focusing
  • You are preoccupied with thoughts of death
  • You experience severe mood changes or decreased energy during winter months

How K Health Can Help

Think you might need a prescription for Wellbutrin (bupropion) or a prescription for Zoloft (sertraline)?

K Health has clinicians standing by 24/7 to evaluate your symptoms and determine which prescription is right for you.

Get started with our free assessment, which will tell you in minutes if treatment could be a good fit. If yes, we’ll connect you right to a clinician who can prescribe medication and have it shipped right to your door.

Frequently Asked Questions

Are Wellbutrin and Zoloft the same?
While Wellbutrin and Zoloft are both antidepressant medications that can be used to treat depression, they are not the same drug. They have different active ingredients that help manage depressive disorders in different ways.
Should I take Wellbutrin and Zoloft together?
Taking Wellbutrin and Zoloft together may work well for some patients, but it can also increase the risk of seizures. Always make sure to talk to your doctor before making any changes to your drug regimen.
Does Wellbutrin work faster than an SSRI?
Most patients see some form of improvement within the first 1-2 weeks of taking Wellbutrin (an NDRI), and the same goes for Zoloft (a SSRI).
Do Zoloft and Wellbutrin cause weight gain?
It's possible. Some research shows a link between taking antidepressant medications, like Zoloft and Wellbutrin, and weight gain. On the other hand, some studies show that Wellbutrin can cause weight loss. If you are concerned about gaining weight while taking Zoloft or Wellbutrin, try to maintain normal, healthy eating habits and stay active. If you noticed significant weight gain or weight loss, tell your doctor. They can help make the best recommendations for your unique scenario.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Arielle Mitton

Dr. Mitton is a board certified internal medicine physician with over 6 years of experience in urgent care and additional training in geriatric medicine. She completed her trainings at Mount Sinai Hospital and UCLA. She is on the board of the Hyperemesis Research Foundation to help women suffering from hyperemesis gravidarum.

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