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Zoloft vs Wellbutrin: Differences, Similarities, and Which Is Better for You

Similarities and differences of Wellbutrin and Zoloft
Written by:

Rabia Khaliq

MSc in Applied Psychology


Medical Disclaimer
The medications listed on this website are provided for informational purposes only. Their inclusion does not guarantee that they will be prescribed to any individual, as treatment decisions are ultimately at the discretion of healthcare providers. This list is not exhaustive, and healthcare providers may prescribe other medications, including non-stimulant options, based on the patient’s unique health circumstances and needs. Read more

In recent years, the prevalence of depression and anxiety has become a growing concern globally. According to the World Health Organization, depression affects 5% of people [1*] and anxiety impacts 4% of individuals [2*] worldwide.

When considering treatments for depression and anxiety, two commonly prescribed medications are Wellbutrin and Zoloft, or bupropion and sertraline, respectively. Understanding how sertraline differs from bupropion and their similarities is crucial for making an informed choice about your mental health treatment.

Confused about choosing Zoloft or Wellbutrin? Let us help you compare these medications and select the most effective one for you.

Basic Facts About Wellbutrin

Wellbutrin, known scientifically as bupropion hydrochloride, is primarily used for treating major depressive disorder and seasonal affective disorder. It is also prescribed to aid in smoking cessation. Its mechanism of action differs from many antidepressants. Wellbutrin works by increasing the levels of norepinephrine and dopamine in the brain, neurotransmitters that play a key role in mood regulation.

Basic Facts About Zoloft

Zoloft, or sertraline [3*] , is another widely used medication for depression. Beyond depression, it is effective in treating a range of anxiety disorders, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). Zoloft belongs to the class of medications known as selective serotonin reuptake inhibitors (SSRIs). It works by preventing the reabsorption of serotonin in the brain, a neurotransmitter that influences mood. 

Key Similarities

Zoloft and Wellbutrin have several key similarities, which are important to consider when evaluating treatment options for mental health conditions.

  1. Primary function. Both Zoloft and Wellbutrin are primarily used to treat major depressive disorders. Their main objective is to alleviate symptoms of depression and improve mood.
  2. Administration method. Both medications are administered orally, making them convenient for outpatient treatment.
  3. FDA approval. Both Zoloft and Wellbutrin have received approval from the U.S. Food and Drug Administration (FDA), highlighting their effectiveness and safety for treating depression when used as directed and under medical guidance.
  4. Risk of physiological dependency. Neither Zoloft nor Wellbutrin is classified as addictive. However, both can lead to physiological dependence in the case of long-term use. This means that while they do not cause cravings typically associated with addiction, stopping them abruptly can lead to withdrawal symptoms.
  5. Withdrawal effects risk. Both medications carry the risk of discontinuation syndrome if they are stopped abruptly. Gradual tapering is often recommended to minimize these withdrawal effects.
  6. Target demographic. Mental health professionals prescribe Wellbutrin and Zoloft to adults. Additionally, Zoloft can be safe for use in children over 6 years, making it a viable option for pediatric patients with certain conditions.
  7. Treatment beyond depression. Besides major depressive disorder, both medications are used for other mental health conditions. Zoloft is effective for various anxiety disorders, PTSD, and OCD, while Wellbutrin is also used for seasonal affective disorder and as an aid in smoking cessation.

Key Differences

It would be wrong to say that Zoloft and Wellbutrin are the same. When evaluating treatment options for mental health conditions, understanding the specifics of medications like Zoloft and Wellbutrin is crucial. This detailed comparison provides essential information to help in making an informed decision.

Key components



Generic Name



Forms Available

– Oral tablet

– Oral solution

– Immediate-release tablet

– Sustained-release tablet (Wellbutrin SR)

– Extended-release tablet (Wellbutrin XL)

Typical Dosages

– Tablets: 25 mg, 50 mg, 100 mg

– Oral solution: 20 mg/mL

50 mg once per day (with variations based on the release type)

Administration Method



Safe for

– Adults

– Children over 6 years

– Children

– Adolescents

– Adults

Risk of Addiction

No, but long-term use can lead to physiological dependency

No, but long-term use can lead to physiological dependence

Withdrawal Effects Risk

Yes, discontinuation syndrome is possible after sudden discontinuation

Yes, discontinuation syndrome is possible after abrupt discontinuation

Drug Class

SSRI (selective serotonin reuptake inhibitor)

NDRI (norepinephrine-dopamine reuptake inhibitor)

FDA Approval

Yes, since 1991

Yes, since 1985

Conditions Treated by Wellbutrin and Zoloft

Wellbutrin is often recognized for its effectiveness in treating depression and its unique ability to assist in smoking cessation. On the other hand, Zoloft is known for its broad application in treating a range of anxiety disorders and other related conditions.

Here is a comparison table highlighting the conditions each medication is typically used to treat:




Major Depressive Disorder



Generalized Anxiety Disorder (GAD)



Attention deficit hyperactivity disorder (ADHD)



Obsessive-Compulsive Disorder (OCD)



Panic Disorder



Post-Traumatic Stress Disorder (PTSD)



Premenstrual Dysphoric Disorder (PMDD)



Social Anxiety Disorder (SAD)



Smoking Cessation



Navigate any health challenge with confidence, guided by our medical professionals who offer expert, personalized treatment for your unique needs.

Side Effects of Zoloft vs Wellbutrin

Zoloft, as an SSRI, and Wellbutrin, as an NDRI, have distinct mechanisms of action, which contribute to their differing side effects. It is important to consider these when selecting a medication, as side effects can impact daily life and overall treatment satisfaction.

Here is a comparison table of the side effects commonly associated with each medication:

Side Effect




Yes (26%)

Yes (13%)

Dry Mouth

Yes (14%)

Yes (17%)


Yes (7%)

Yes (6%)


Yes (20%)

Yes (4%)


Yes (4%)

Yes (5%)


Yes (12%)

Yes (7%)


No (n/a)

Yes (26%)

Weight Loss

No (n/a)

Yes (14%)

Weight Gain

No (n/a)

Yes (3%)


Yes (6%)

Yes (10%)




Drug Interactions of Wellbutrin vs Zoloft

Wellbutrin (bupropion) and Zoloft (sertraline) have different pharmacological profiles, leading to varied interactions with other medications. Wellbutrin, as an NDRI, primarily affects norepinephrine and dopamine reuptake, whereas Zoloft, as an SSRI, mainly influences serotonin levels. These mechanisms of action can lead to different interactions when combined with other medications.

Below is a comparison table that highlights some key drug interactions for Wellbutrin and Zoloft:

Drug/Drug Class

Interaction with Wellbutrin

Interaction with Zoloft

MAO Inhibitors

Severe risk of hypertensive crisis; contraindicated

Severe risk of serotonin syndrome; contraindicated

Tricyclic Antidepressants

Increased risk of side effects due to elevated levels of TCA

Possible increase in TCA levels; monitoring recommended


Potential altered benzodiazepine response

Potentially increased plasma levels of benzodiazepines


Increased risk of neuropsychiatric side effects and seizures

Increased sedation and impairment; risk of enhanced depression symptoms


Risk of increased side effects or lowered seizure threshold

Possible increase in antipsychotic plasma levels; risk of QT prolongation


Possible increased concentration of beta-blockers

No significant interaction noted

CYP2D6 Inhibitors (e.g., Fluoxetine, Paroxetine)

Increased Wellbutrin levels, heightened risk of adverse effects

Possible increase in Zoloft levels, enhanced side effects

CYP2B6 Inducers (e.g., Rifampin, Carbamazepine)

Reduced efficacy of Wellbutrin

No significant interaction noted


Possible altered prothrombin time

Possible increased bleeding risk; monitoring recommended

Serotonergic Drugs (e.g., Triptans, Tramadol)

No significant interaction noted

Risk of serotonin syndrome; use with caution

How Should Wellbutrin and Zoloft Be Taken?

Proper administration of medication is as crucial as the medication itself. When it comes to antidepressants like Wellbutrin and Zoloft, understanding the correct way to take them can significantly impact their effectiveness and the overall treatment experience. Let’s explore the recommended guidelines for taking these medications.


  • Dosage. Wellbutrin doses vary depending on the specific formulation (immediate-release, sustained-release, or extended-release) and the individual’s response to treatment. It’s typically started at a low dose and gradually increased.
  • Administration. It should be taken orally, with or without food. The time of day can vary based on the prescribed form and individual side effects (e.g., insomnia).
  • Duration. The full effect may take several weeks. It is crucial to continue taking Wellbutrin as prescribed, even if symptoms improve.
  • Missed dose. If a dose is missed, it should be taken as soon as remembered unless it’s close to the time of the next dose. Do not double the dose to catch up.


  • Dosage. The initial dose is usually low, gradually increasing to the effective dose. Dosage may vary based on the condition being treated.
  • Administration. Zoloft is taken orally, with or without food. Consistency in the time of taking the medication daily is recommended for best results.
  • Duration. As with Wellbutrin, it may take several weeks to feel the full benefits. Continuation of the medication as prescribed is important.
  • Missed dose. If a dose is missed, take it as soon as you remember. However, skip the missed dose if it is almost time for the next dose. Never double up doses.
Choosing your medication shouldnэt be a guesswork. Consult with us to understand if Zoloft or Wellbutrin is right for you.

Warnings & Associated Risks of Zoloft & Wellbutrin

Awareness of the potential warnings and risks associated with medications is a key component of informed healthcare. Wellbutrin and Zoloft, while effective in treating various mental health conditions, come with their own set of warnings and risks that patients and healthcare providers should be aware of. These warnings are essential for ensuring the safe use of these medications.


  • Seizure risk. Higher risk in patients with a seizure disorder, eating disorders, or those undergoing abrupt withdrawal from alcohol or sedatives.
  • Suicidal thoughts. As with many antidepressants, there may be an increased risk of suicidal thoughts, especially in young adults and children.
  • Interactions. Wellbutrin can interact with a variety of medications and may increase the risk of hypertension in combination with certain medications.


  • Serotonin syndrome. Zoloft increases risk if taken with other serotonergic drugs. Symptoms include high fever, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea.
  • Suicidal thoughts. Similar to Wellbutrin, increased risk in younger patients.
  • Withdrawal symptoms. Abrupt discontinuation may lead to withdrawal symptoms such as mood swings, irritability, agitation, dizziness, sensory disturbances, and headache.
  • Pregnancy and nursing. Zoloft can pass into breast milk and may have undesirable effects on a nursing infant. There are also risks associated with taking Zoloft during pregnancy.

Wellbutrin or Zoloft: Which Is More Effective?

Determining which medication is more effective, Wellbutrin or Zoloft, depends largely on the individual’s specific condition and their unique response to each medication. While both are effective for treating depression, their mechanisms of action and thus their effectiveness can vary greatly from person to person.

  • For depression. Both are proven effective, but the choice may depend on patient-specific factors such as the presence of anxiety, which may respond better to Zoloft when treating depression.
  • For anxiety disorders. Zoloft is typically preferred due to its efficacy in treating a range of anxiety-related conditions. Wellbutrin can be prescribed for anxiety as the second or third treatment option, but its effectiveness is still not clear.
  • For smoking cessation. Wellbutrin is the clear choice, as it is one of the few antidepressants shown to be effective in helping with smoking cessation.
  • Side effect profile. The decision may also be influenced by the side effect profiles of each medication and how the patient tolerates them.

Ultimately, the decision between Wellbutrin and Zoloft should be made in consultation with a healthcare provider, considering the individual’s medical history, current health condition, and treatment response.

Which One Works Faster or Lasts Longer?

The onset of action and the duration of effect are important considerations when choosing between Wellbutrin and Zoloft [4*] . These factors can affect how quickly relief is felt and the long-term management of symptoms.


  • Onset of action. Some patients may begin to notice improvements in their symptoms within the first week or two, but it generally takes about 4-6 weeks to experience the full benefits.
  • Duration of effect. Wellbutrin has a sustained effect throughout the day, particularly the extended-release versions, which are designed to maintain stable medication levels in the body over a longer period.


  • Onset of action. Like Wellbutrin, initial improvements with Zoloft may be noticed within the first few weeks, but it usually takes 4-6 weeks to feel the full effect.
  • Duration of effect. Zoloft’s effects are also sustained throughout the day. Its half-life allows for once-daily dosing, contributing to steady levels in the bloodstream.

Which Is Better for Short-Term and Long-Term Use?


  • Short term. Effective for acute episodes of depression; also beneficial for short-term smoking cessation programs.
  • Long term. Can be used for chronic depression management. Its relatively lower risk of sexual side effects makes it a preferred option for long-term use by some patients.


  • Short term. Useful in acute anxiety and depressive episodes.
  • Long term. Considered safe and effective for long-term treatment of chronic anxiety disorders, OCD, PTSD, and depression.

Can You Take Wellbutrin & Zoloft Together?

Combining Wellbutrin and Zoloft is a strategy sometimes employed by healthcare providers in what is known as “augmentation therapy.” This approach can be effective, especially in cases where symptoms are not adequately managed by a single medication.

  • Safety and efficacy. The combination can be safe and effective, but it should only be done under close medical supervision due to the increased risk of side effects and drug interactions.
  • Synergistic effect. The differing mechanisms of action of Wellbutrin and Zoloft can complement each other, potentially leading to better treatment outcomes in certain patients.
Discover which medication, Zoloft or Wellbutrin, may be more effective for you. Our team is here to provide expert guidance and support.

Bottom Line

The choice whether to prescribe Zoloft or Wellbutrin should be tailored to individual health needs and preferences. Wellbutrin is often favored for its activating effects and utility in smoking cessation, while Zoloft is renowned for its efficacy in treating a broad spectrum of anxiety disorders and depression, and its established long-term safety profile.

There are other meds that can help you even better, for example, Wellbutrin is often compared to Lexapro for depression and Zoloft can be replaced by Sertraline for anxiety. Healthcare professionals at MEDvidi can guide you and determine the most suitable option for your effective mental health management.


Neither Wellbutrin nor Zoloft is typically associated with significant weight gain. In fact, Wellbutrin is sometimes associated with weight loss. Zoloft, however, may lead to weight changes in some individuals, but this is not a common side effect.
Individuals with seizure disorders, a history of eating disorders, or those undergoing abrupt withdrawal from alcohol or sedatives are generally not good candidates for Wellbutrin due to an increased risk of seizures. Additionally, those with a known hypersensitivity to bupropion (the active ingredient in Wellbutrin) should avoid it. You should get acquainted with Wellbutrin and Zoloft precautions to make sure the medication will not do you any harm.

A switch from Zoloft to Wellbutrin may be considered if a patient experiences intolerable side effects with Zoloft, such as sexual dysfunction [5*] or weight gain, or if Zoloft is not effectively managing their symptoms. Wellbutrin is different from Zoloft, as its mechanism of action and side effect profile may be more suitable for some individuals.

Healthcare specialists can prescribe Wellbutrin to replace Zoloft for some individuals. Especially if they are seeking an alternative due to specific side effects of Zoloft, like sexual dysfunction. Also, if they require medication with a different mechanism of action. However, suitability varies based on individual health needs and response to medication.

Wellbutrin is not necessarily stronger than Zoloft; rather, it works differently. Each medication has its own strengths and is effective for different symptoms and conditions. The perceived “strength” of a medication can vary depending on individual responses and the specific condition being treated.


5 sources
  1. Depressive disorder (depression)
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  2. Anxiety disorders
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  3. Zoloft
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  4. Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients?
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  5. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline
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Written by:

Rabia Khaliq

MSc in Applied Psychology


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This article is based on scientific evidence, written by experts and fact checked by experts.

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This article contains scientific references. The numbers
in the parentheses (1, 2, 3) are clickable links to peer-reviewed scientific papers.