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Zoloft and Wellbutrin are prescription drugs that are used to treat common mental health conditions like major depressive disorder, generalized anxiety disorder, social anxiety disorder, seasonal affective disorder (SAD), obsessive-compulsive disorder (OCD), separation anxiety disorder, panic disorder, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). While both medications are used to treat some of the same conditions, they act differently. 

Please continue reading to find out the key differences between Wellbutrin and Zoloft and which one may be better for you.

What is a selective serotonin reuptake inhibitor (SSRI)?

Selective serotonin reuptake inhibitors (SSRIs) are a group of commonly prescribed antidepressant drugs that inhibit the reabsorption of serotonin by neurons. Serotonin is a chemical messenger in the brain that works as a mood stabilizer. By increasing the availability of serotonin, SSRIs help to regulate mood. Zoloft (generic name sertraline) is an SSRI. 

Wellbutrin (generic name bupropion) belongs to a different class of medications called NDRIs (norepinephrine-dopamine reuptake inhibitors). NDRIs and SSRIs act similarly, i.e., they boost the levels of certain chemicals called neurotransmitters in the brain. However, SSRIs such as Zoloft boost serotonin levels. NDRIs such as Wellbutrin boost norepinephrine and dopamine levels. 

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What conditions do Wellbutrin and Zoloft treat?

Major Depressive Disorder

Also called major depression, this is a condition that impacts mood and behavior. Both Wellbutrin and Zoloft are used to treat major depressive disorder.

Seasonal Affective Disorder (SAD)

This is a type of depression that is linked to seasonal changes. Wellbutrin is used to treat SAD, while Zoloft is not.

Obsessive-Compulsive Disorder (OCD)

This disorder is characterized by recurring thoughts and ideas (obsessions) that drive a person to do something repetitively (compulsions). Zoloft is used to treat OCD, but Wellbutrin is not. 

Social Anxiety Disorder

This mental health condition is associated with intense and persistent fears of being watched and judged by others. It can affect all aspects of a person’s life. Zoloft is a treatment for social phobia, but not Wellbutrin.

Generalized Anxiety Disorder (GAD)

This condition is characterized by exaggerated worries about everyday events related to family, health, money, work, etc., with no apparent reasons or causes. Zoloft is sometimes used to treat GAD, but it is an off-label use, meaning it is not FDA-approved for this particular indication. Wellbutrin is not used to treat GAD.

Panic Disorder

This is one of several types of anxiety disorders. It is associated with sudden unreasonable attacks of fear and anxiety that cause physical symptoms like excessive sweating and racing, pounding heartbeats. While Zoloft is used to treat panic disorder, Wellbutrin is not. 

Smoking Cessation

Taking Wellbutrin can help you to stop smoking. However, scientists do not entirely understand how Wellbutrin is effective for smoking cessation. Notably, Wellbutrin can cause more side effects than other smoking cessation treatments.

Wellbutrin and Zoloft: How are they similar?

Both Wellbutrin Zoloft can help to regulate mood and treat depressive symptoms. They are available in generic and brand name versions. Both are prescription drugs that come in the form of oral tablets to be taken by mouth. They can be used long-term (months to years) by depressed patients. Wellbutrin / Zoloft are both approved for use in adolescents and adults. 

Zoloft, or any other SSRIs, and bupropion (Wellbutrin) should not be taken together with a monoamine oxidase inhibitor (MAO inhibitor). Examples of monoamine oxidase inhibitors are isocarboxazid, phenelzine, selegiline, and procarbazine. A 14-day wash-out period when switching between Zoloft, Wellbutrin, and an MAO inhibitor is crucial to avoid serotonin syndrome. Serotonin syndrome can cause confusion, tremors, high blood pressure, coma, and even death. This is a medical emergency that requires urgent medical care.

Wellbutrin vs. Zoloft: What’s the difference?

The most important difference in drug information for Wellbutrin and Zoloft is that they contain different active ingredients. Wellbutrin contains bupropion, and Zoloft contains sertraline. As noted, they belong to different drug classes - Wellbutrin is an NDRI, and Zoloft is an SSRI. Bupropion and sertraline differ because they act on different chemical messengers in the brain. Wellbutrin boosts norepinephrine and dopamine, and Zoloft increases the availability of serotonin. They are approved to treat different psychiatric disorders, as listed above. 

Zoloft is available as an oral tablet and liquid form. Wellbutrin is available as extended-release tablets and sustained-release tablets that allow once-daily dosing. The typical dose of Zoloft is 50 mg once daily. The usual dose of Wellbutrin is 150 mg XL once a day. Zoloft is an approved antidepressant medication in children.  Wellbutrin is not typically prescribed to children younger than 18 years of age.

Wellbutrin is a prescription drug that is generally covered by private health insurance plans and Medicare. Out-of-pocket expenses for brand name Wellbutrin XL 150 mg are about $180 per month. However, with a BuzzRx coupon, you can get the generic (bupropion) at a fraction of this price. 

Zoloft is a prescription drug, and it is usually covered by both Medicare and private health insurance plans. It is a more expensive drug with an out-of-pocket cost of around $400 per month for brand-name Zoloft. A coupon from BuzzRx can help you obtain the medication at a hugely discounted price. 

Which antidepressant is the strongest?

Studies that have compared antidepressant efficacy have found that Zoloft and Wellbutrin do not differ significantly in terms of effectiveness, tolerability, and side effects. Besides depressive symptoms, research has also shown that the two drugs have comparable effects in relieving anxiety disorders. They were also found to have an equally rapid onset of benefits. Improvement in symptoms can be seen as early as 2 weeks after therapy initiation.

Both bupropion (Wellbutrin) and sertraline (Zoloft) are considered safe and effective treatments. Choosing the best antidepressant medications often comes down to the type of mental health condition you have, the potential side effects of the medications, drug interactions, and your general medical history. 

For example, some people prefer Wellbutrin because it is less likely to cause adverse effects like problems with sexual function or drowsiness. Others may prefer the fact that sustained-release bupropion allows less frequent dosing. Your healthcare professional may decide on one or the other medication depending on your other medications, according to what drugs interact. 

You should seek professional medical advice to determine which is better for you, Wellbutrin vs. Zoloft.

Frequently Asked Questions

Is Wellbutrin the best antidepressant?

Wellbutrin (bupropion hydrochloride) is an effective antidepressant medication comparable to other selective serotonin reuptake inhibitors (SSRIs) and other classes of antidepressants. It is well tolerated for both short- and long-term treatment of depression. Common side effects of Wellbutrin include dry mouth, headache, dizziness, nausea, constipation, and insomnia. Severe adverse reactions related to Wellbutrin are rare. 

One of the advantages of Wellbutrin is that among the newer antidepressant medications available in the U.S. and compared to other drugs, it is less likely to cause sexual dysfunction such as decreased libido, erectile dysfunction, and premature ejaculation. Wellbutrin is also less likely to cause weight gain and drowsiness. It is approved by the U.S. Food and Drug Administration (FDA) to treat major depressive disorder, seasonal affective disorder, and smoking cessation.

Is Wellbutrin good for social anxiety?

Bupropion (Wellbutrin) has been evaluated for the use of generalized social phobia. People who took this medicine reported feeling much improved or very much improved after 12 weeks of treatment. This medication was generally well tolerated. Findings from this study suggest that bupropion-SR can be useful in treating generalized social phobia.

What is better than Zoloft for anxiety?

Zoloft has been shown by placebo-controlled clinical studies to effectively treat major depression, anxiety disorders, panic disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), seasonal affective disorder (SAD), and premenstrual dysphoric disorder (PMDD).

For anxiety disorders, another selective serotonin reuptake inhibitor (SSRI) called Lexapro (escitalopram) may be more effective and better tolerated than Zoloft. However, other studies have found that Zoloft had equally good or better outcomes than Lexapro. 

Only your healthcare provider should determine the best antidepressant medication for you after considering your health history, medications, and allergies. You should discuss with your primary care doctor to evaluate the risks vs. benefits of each treatment option to determine which medication is the best option for you.