Wellbutrin Vs. Zoloft: Key Differences & Choosing the Best for You

Key Differences Between Wellbutrin vs. Zoloft

Wellbutrin (bupropion) and Zoloft (sertraline) are FDA-approved medications effective for relieving symptoms of depression. While the medications work the same way to treat MDD, they are antidepressants that belong to a different class of drugs. Wellbutrin is an NDRI (norepinephrine and dopamine reuptake inhibitor) medication, while Zoloft is an SSRI (selective serotonin reuptake inhibitor) antidepressant.^2,3

These medications can be prescribed by:

• Licensed nurse practitioners
• Primary care providers
• Clinicians
• Licensed physician assistants
• Psychiatrists

The table below compares the different components of each medication:^1,2

Key Components	Zoloft	Wellbutrin
What is the Generic Name?	Sertraline	Bupropion
What forms does it come in?	Oral tablet Oral solution	Immediate-release Sustained-release Extended-release tablet
What are the typical dosages?	Tablets: 25mg 50mg 100mg Oral solution: 20mg/mL	50mg once per day
How is it administered?	Orally	Orally
Who is safe to take it?	Adults Children over 6 years	Children Adolescents Adults
Is there a risk of addiction?	No, but long-term use can lead to physiological dependency.	No, but long-term use can lead to physiological dependence.
Is there a risk of withdrawal effects?	Yes. Zoloft can lead to discontinuation syndrome after sudden discontinuation.	Yes. Wellbutrin can lead to discontinuation syndrome after abrupt discontinuation.
Drug class	SSRI	NDRI
FDA approved	Yes. Initial U.S. Approval: 1991	Yes. Initial U.S. Approval: 1985

How Do Zoloft & Wellbutrin Work?

Zoloft belongs to the SSRI class of drugs, which works by altering brain chemistry. Zoloft treats depression by regulating the levels of serotonin in the brain. The antidepressant blocks the reabsorption and breakdown of serotonin in the body leading to an increased serotonin level in the brain. This helps to influence your mood, behavior, and depression, making you feel better.⁴

Wellbutrin is a norepinephrine and dopamine reuptake inhibitor that affects how the body produces neurotransmitters crucial for transporting messages between the body’s nerve cells. Wellbutrin works by blocking the reuptake and breakdown of norepinephrine and dopamine. This increases the amount of norepinephrine and dopamine in the body, potentially relieving symptoms of depression.

While both medications work the same in treating symptoms of depression, your doctor may consider one over the other. Your prescriber can consider Wellbutrin over Zoloft or vice versa depending on the following factors:

• Nature of your condition
• The side effects of the medication
• Treatment duration
• The efficacy of the medication

What Are Wellbutrin & Zoloft Used to Treat?

Sertraline can be prescribed as an on-label use as a medication for anxiety, depression, and other medical conditions. The medication can also treat other disorders such as obsessive-compulsive disorder in children, binge eating disorder, and generalized anxiety disorder as off-label use (non-FDA approved). Off-label drug use prescribes a particular purpose than what the FDA approved.³
Talk with your doctor before you take Zoloft for off-label use.

Wellbutrin (Bupropion) is an FDA-approved medication for major depressive disorder. Bupropion is used as an on-label medication for managing depressive symptoms. The medication can also be used for off-label (not FDA-approved) treatment of other conditions, including antidepressant-induced sexual dysfunction and attention-deficit/hyperactivity disorder (ADHD). Wellbutrin can also be used for off-label treatment of depression associated with bipolar disorder.^1,4

Who Should Take Zoloft or Wellbutrin?

Before taking Zoloft or Wellbutrin medication, you should talk with your prescriber to ensure the drug is suitable for your condition. These medications are not recommended for people who have certain risk factors. This is due to the adverse side effects, including risks of suicidal thoughts and behaviors associated with the medications. If you have depression or anxiety, your doctor will check for symptoms such as sadness, sleep problems, and loss of interest to prescribe medication. Also, the nature of your condition will influence whether you are prescribed Zoloft or Wellbutrin.

The table below compares the different medical conditions used for each medication:^2,3

Condition	Zoloft	Wellbutrin
Depression	Yes	Yes
Generalized anxiety disorder (GAD)	Off-label	No
Premature ejaculation	No	No
Attention deficit hyperactivity disorder (ADHD)	No	Off-label
Obsessive-compulsive disorder (OCD)	Yes	No
Panic disorder	Yes	No
Post-traumatic stress disorder (PTSD)	Yes	No
Premenstrual dysphoric disorder (PMDD)	Yes	No
Social anxiety disorder (SAD)	Yes	No
Smoking cessation	No	Yes

Side Effects of Zoloft Vs. Wellbutrin

When taking Zoloft or Wellbutrin for depression, you may experience side effects as your body adjusts to the medication.⁴ This may be a key factor influencing your choice of medication. These side effects are not severe and do not usually require immediate medical help. The medication’s side effects generally emerge within the first or second week of your initial dosage. However, if the side effects become intolerable, seek help from your doctor.

The table below compares the different medical conditions used for each medication:^2,3

Side Effects	Zoloft	Wellbutrin
Nausea	Yes, (26%)	Yes, (13%)
Dry mouth	Yes, (14%)	Yes, (17%)
Sweating	Yes, (7%)	Yes, 6%)
Vomiting	Yes, (20%)	Yes, (4%)
Diarrhea	Yes, (4%)	Yes, (5%)
Dizziness	Yes, (12%)	Yes, (7%)
Headache	No, n/a	Yes, (26%)
Weight loss	No, n/a	Yes, (14%)
Weight gain	No, n/a	Yes, (3%)
Constipation	Yes, (6%)	Yes, (10%)

Severe Side Effects & Allergic Reactions

While not common, Wellbutrin or Zoloft use can lead to severe side effects that may be life-threatening. The severe side effects, including serotonin syndrome and suicidal ideation and behaviors, require immediate medical attention. Severe side effects of the medications can occur due to several factors, including age, health condition, and interactions with other substances or medications. Allergic reactions may also occur, most often for those with a history of allergic reactions to antidepressants such as Pristiq.

Insurance Coverage and Cost Effectiveness

The drug’s cost can influence your choice of depression medication. If the cost is too high, you might consider a cheaper alternative. Wellbutrin XL 150mg costs about $180. Both commercial and Medicare drug plans cover the medication. You can get the drug with a typical Medicare copay of about $10 or less. Also, you can get Wellbutrin for a reduced price of less than $12 if you are using a coupon from providers like SingleCare

Generally, the price of Zoloft can be over $400. This can be expensive for most people. Both Medicare and many insurance plans cover the drug. If you have Medicare insurance, you can get the medication at a reduced price of about $10 or less. Also, you can get Zoloft for about $10 if you purchase it using coupons from providers like SingleCare.

Warnings & Associated Risks of Zoloft & Wellbutrin

Before starting your Zoloft or Wellbutrin medication, talk with your doctor to understand the risks and benefits of the medications. Also, share with your doctor about your medical history and if you have other complications before you are prescribed the medication. This will help address safety concerns and increase the safety of either Wellbutrin or Zoloft medication.

While these medications can be effective at relieving symptoms of depression, they can worsen or negatively impact the body, especially if you have preexisting medical conditions such as liver or kidney problems. Certain groups of people, particularly children, are not typically prescribed either medication due to the increased risk of suicidal thoughts and behaviors. Pregnant or breastfeeding women may be at increased risk of birth defects or preterm labor when taking the medications. Also, stopping either medication abruptly may lead to antidepressant discontinuation syndrome.

The table below compares the medical conditions you should discuss with your doctor before taking Wellbutrin or Zoloft:^2,3

Medical Conditions	Zoloft	Wellbutrin
Liver problems	X	X
Suicidal ideation	X	X
Pregnancy	X	X
Breastfeeding	X	X
Bleeding problems	X	X
Heart issues	X	X
Glaucoma	X	X

Interactions for Wellbutrin & Zoloft

Disclaimer: Taking certain medications, herbs, or supplements alongside Wellbutrin and Zoloft can change how Wellbutrin and Zoloft work in your body or increase the risk for serious side effects. This article does not consider all the possible interactions. Please let your doctor, psychiatrists, and pharmacists know about all the products you currently use, such as prescription medication, nonprescription drugs, and herbal supplements. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Like other medications or antidepressants, Wellbutrin or Zoloft can negatively interact with other substances. Even though Sertraline and Bupropion work the same way to manage depressive symptoms, these medications have unique chemical components that play a role in the varied side effects. Wellbutrin and Zoloft risk mixing with other substances, medications, or dietary supplements as their side effects can be life-threatening.

Substances that have harmful interactions with Wellbutrin and Zoloft include:^2,3

Complicating Interactions	Zoloft	Wellbutrin
Blood thinners	X	X
NSAIDs	X	X
MAOIs	X	X
Other depression medications	X	X
Alcohol	X	X
Water pills	X	X
Benzodiazepines	X	X
Migraine medications	X	X
Pimozide	X	X
Thioridazine	X	X
St John’s Wort	X	X

Wellbutrin or Zoloft: Which is More Effective?

Your prescriber will consider several factors, including tolerability, efficacy, and depression remission, to prescribe one medication over the other. A randomized study compared depression remission and tolerability of three antidepressants. This included Bupropion, Sertraline, and Venlafaxine. The controlled trial study focused on patients with depression that was not responsive to other medications. The study found both antidepressants, Bupropion, Sertraline, and Venlafaxine, to be effective with no significant difference in remission rates, tolerability, or severe events.¹

Side effects are also a key factor when choosing between Wellbutrin or Zoloft. Evaluating what antidepressants can make you feel like is an important consideration, as experiencing too many side effects could discourage you from taking your medication as prescribed.

Which One Works Faster or Lasts Longer?

Understanding how long antidepressants take to work is an essential part of the initial adjustment to the medications. Antidepressant medications usually take different timelines, usually between 6 to 8 weeks, to effectively improve symptoms of depression or other conditions.⁵
Additionally, clinical trials have found both Wellbutrin and Zoloft to have no major difference in effectiveness.

Dosage forms for Wellbutrin include:²

• Extended-release tablet
• Immediate release
• Sustained release tablet

Dosage forms for Zoloft:³

• Oral tablet
• Oral solution

Which Is Better for Short Term or Long Term Use?

Bupropion and Sertraline can be used for either the short term or long term, depending on the nature of your condition. However, Wellbutrin is usually prescribed for short-term use as it is effective at relieving depressive symptoms with minimal sexual side effects. Sertraline is often recommended for long-term use as it is effective at preventing the recurrence of depression and anxiety. Talk with your doctor to understand which medication is best for your condition.

Can You Take Wellbutrin & Zoloft Together?

It’s possible to take Wellbutrin and Zoloft together for depression as prescribed by your doctor. Using the medications together can have added benefits to some people, as they work to influence different neurotransmitters in the brain. This can help improve symptoms of depression, making you feel better.

However, using Wellbutrin and Zoloft together may increase the risk of side effects and drug interactions. You may experience severe headaches and drowsiness. In extreme cases, the medications can lead to overdose, which can be life-threatening. Talking with your doctor before using the medications is paramount to prevent further health complications.

Questions to Ask Your Health Team About Wellbutrin Vs Zoloft

If you are considering either Wellbutrin or Zoloft for depression, consult your doctor for more medication assistance. Talk with your doctor about your medical history to ensure everything is considered before beginning your dosage. You can ask your doctor how long the medication’s side effects last or the dangers of mixing the medications with other substances.

Here are 11 questions to ask your care team when considering Wellbutrin or Zoloft:

• Is it safe to take Wellbutrin or Zoloft with other medications?
• Will my insurance cover Wellbutrin or Zoloft?
• Which one has the best results as a treatment for depression?
• Does my medical history increase my increase of side effects for either?
• How long can I expect side effects to last?
• Which one is the best for my treatment of anxiety?
• How often should I see you for checkups while taking Wellbutrin vs. Zoloft?
• What should I do if I am unsure if psychotropics are right for me?
• What are the best online psychiatry options to get a prescription?
• Are there risks associated with taking Wellbutrin or Zoloft with substances like alcohol?
• Can I take Wellbutrin and Zoloft together?
• What are some alternatives to Wellbutrin?
• How effective is sertraline for premature ejaculation?

Final Thoughts

Antidepressant medications such as Wellbutrin and Zoloft can be effective at relieving symptoms of depression. The medications are commonly prescribed based on tolerability, side effects, efficacy, and remission rates. However, these medications are associated with common  side effects that can worsen depending on age and health condition. Before starting either medication, talk with your doctor to understand the risks associated with the drugs. This will address safety concerns and ensure you are safe on medication.

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