Wellbutrin Vs. Zoloft


Wellbutrin is a Norepinephrine–Dopamine Reuptake Inhibitor (NDRI) and Nicotinic Acetylcholine (NACH) receptor antagonist. On the other hand, Zoloft is a Selective Serotonin-Reuptake Inhibitor (SSRI). Both drugs impact levels of neurotransmitters in the brain, but they act in different ways and on different pathways/neurotransmitters. Wellbutrin primarily alters the norepinephrine and dopamine hormone levels, and Zoloft alters the serotonin levels.

About Wellbutrin Vs. Zoloft

Wellbutrin is commonly known as bupropion, given to patients with seasonal affective disorder and Major Depressive Disorder (MMD). It works on neuronal levels, activating the re-update inhibitors for norepinephrine and dopamine. Higher levels of both chemicals are known to improve mood.

Zoloft is commonly known as sertraline and is given to patients to treat depression. It works at your neuronal synapse, blocking the reuptake of serotonin. More serotonin means that your energy and mood levels can be increased.

What Is Wellbutrin?

Wellbutrin is a well-known atypical antidepressant, working as a Norepinephrine–Dopamine Reuptake Inhibitor (NDRI). It improves mood and well-being by restoring natural chemicals called neurotransmitters in the brain.

What Conditions Is Wellbutrin Approved to Treat?

Wellbutrin has been approved by the FDA to treat seasonal affective disorders and depression. It has an active ingredient called bupropion which is also used in Zyban to stop people from smoking.

How Does Wellbutrin Work for Depression?

Researchers have found that Wellbutrin can raise the levels of two chemicals in the brain: dopamine and norepinephrine. This helps improve the symptoms of depression.

What Is Zoloft?

Zoloft is a known anti-depressant, under the umbrella of Selective Serotonin Reuptake Inhibitors. It restores the balance of serotonin in the brain, which can reduce anxiety, fear, panic attacks, and unwanted thoughts.

What Conditions Is Zoloft Approved to Treat?

Zoloft has been approved by the FDA for a variety of conditions in adults. Zoloft is used to treat:

  • Depression
  • Obsessive Compulsive Disorder (OCD)
  • Panic disorder and panic attacks
  • Post-Traumatic Stress Disorder (PTSD),
  • Social Anxiety Disorder
  • Severe Premenstrual Dysphoric Disorder (PMDD)

In adolescents and children above the age of 6, Zoloft has been approved by the FDA to treat OCD.

How Does Zoloft Work for Depression?

Serotonin is a chemical in the brain that impacts many functions of the body, such as regulating anxiety and mood. Zoloft can raise the levels of available serotonin, which can help provide relief from symptoms of depression.

Effectiveness of Wellbutrin and Zoloft

Studies have found that Zoloft is effective in treating depression when compared to placebo pills. Wellbutrin can also treat depression, as studies show it is effective when compared to placebo pills.

Plus, SSRI medications like Zoloft are usually prescribed first when it comes to treating depression.

There have been some studies that compare both medications to see which is more suitable for treating depression. However, there has been no significant difference in how effective they are. A study found they are similarly effective for people who haven't found that other antidepressants don't work. Another controlled, randomized trial by the New England Journal of Medicine compared sertraline (Zoloft), bupropion (Wellbutrin), and venlafaxine. The sample consisted of people who did not respond to other types of treatments. All three were effective, with no differences in adverse events, tolerability, and remission rates.

Conclusively, for patients, you should look at the side effects that the medications can result in. Wellbrutin is less likely to cause somnolence and sexual dysfunction, such as erectile dysfunction, premature ejaculation, and less libido. It is also less likely to result in drowsiness and weight gain, so many healthcare providers and patients prefer Wellbutrin.

How Effective Are Wellbutrin and Zoloft for Treating Anxiety Disorders?

According to a study published in the Lancet Psychiatry, Zoloft can reduce symptoms of anxiety and even self-reported progress in overall mental health within 6 weeks of use. Effectiveness for alleviating depressive symptoms can take longer and are modest in nature.

According to the National Alliance on Mental Illness, Wellbutrin can improve appetite, energy, and sleep in the initial two weeks. A general lack of interest in activities and depressed moods can take 6-8 weeks to improve.

Dosage Information

How Is Wellbutrin Administered for Depression?

It comes in immediate-release pills, available in 75mg and 100mg. It also has a sustained-release version, available in 100mg, 150mg, and 200mg. You can also find an extended-release version that needs to be taken once a day in 150mg and 300mg.

How Is Zoloft Administered for Depression?

Zoloft can be taken orally as a pill, available in 25mg, 50mg, and 100mg. A concentrated, oral solution is available in 20mg/ml too. Usually, it is taken once a day, with the typical starting dose of 50mg. It can be increased if need be.

Contraindications and Interactions for Wellbutrin and Zoloft



Can increase suicidal thoughts and ideation in young adults and teens, especially in the initial stages of treatment until remission is confirmed. Patients must be monitored closely.

Zoloft is placed in the C category for pregnancy by the FDA, which means not enough human studies have been done to determine safety. It should only be used by pregnant mothers if the benefit outweighs the risk to the fetus.


Can increase suicidal thoughts and ideation in young adults and teens, especially in the initial stages of treatment until remission is confirmed. Patients must be monitored closely.

For patients with no previous mental health issues, taking Wellbutrin to quit smoking might experience mental changes when they start. It can include changes in mood, paranoia, hallucinations, anxiety, aggression, and delusions.

It can increase the risk of seizures, so the daily dosage shouldn't be more than 300mg.

Wellbutrin users might also experience increased blood pressure. This can lead to hypertension, even if no cardiovascular events or conditions occurred beforehand.

Drug/Medication Interactions


Zoloft can interact with some drugs due to the metabolism through the cytochrome P450 system. It inhibits the CYP2D6 in a minor way and may cause interactions with substrates of CYP2D6 like codeine, metoprolol, haloperidol, and risperidone at a lesser degree.

Zoloft might cause prolonged QTC interval, known as cardiac arrhythmia if taken with some medication classes.

Taking Zoloft with drugs that result in serotonergic actions can increase serotonin syndrome risk. It is the result of abnormal levels of free serotonin, resulting in dizziness, agitation, and increased heart rate.


Wellbutrin can interact with some drugs due to the metabolism through the cytochrome P450 system. It significantly inhibits the CYP2D6; hence, substrates of CYP2D6 like codeine, metoprolol, haloperidol, and risperidone might be decreased in patients.

Food/Beverage/Supplement Interactions


Eating or drinking grapefruit can affect the effectiveness and adverse events when taking Zoloft.


Foods and beverages containing caffeine, such as energy drinks, chocolate, coffee, tea, sodas, or dietary and herbal supplements, should be limited.

Avoid using alcohol since it can result in potential CNS depressant effects and neuropsychiatric adverse effects.

How Much Do Wellbutrin and Zoloft Cost?

Wellbutrin is often covered by Medicare and commercial drug insurance plants. If you are paying out of your pocket, the 100mg Wellbutrin XL can cost as much as $351 for 30 tablets. For 75mg, it can cost $87 for 30 tablets.

Zoloft is also covered by commercial and Medicare drug plans. If you are paying out of your pocket, it can be $443 for 30 50mg tablets.

Popularity of Wellbutrin and Zoloft

In 2020, sertraline (Zoloft) was prescribed to 38.2 million people in the United States as an antidepressant. On the other hand, in 2020, bupropine (Wellbutrin) was prescribed to 28.9 million people in the US for smoking cessation and antidepressants.


Many clinicians and scientists have agreed that Zoloft and Wellbutrin have similar overall effects and that there aren't any major differences between the two in treating mental illnesses. Both work by regulating chemicals in the brain that impact overall mental health, mood, and energy.

While both drugs have an identical impact on depression, anxiety, and other mental problems, Wellbutrin is less likely to cause side effects like sexual dysfunction and somnolence, so it is preferred by many patients. However, Zoloft can address more mental health problems in children too, so there are a higher number of prescriptions of Zoloft.