Zoloft (sertraline) vs. Wellbutrin (bupropion): What’s the difference?

What are Zoloft and Wellbutrin?

Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI) type antidepressant used to treat depression, obsessive-compulsive disorder (OCD), social anxiety disorder, panic disorder, posttraumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). Other SSRIs include citalopram (Celexa), fluoxetine (Prozac, Sarafem), paroxetine (Brisdelle, Paxil, Paxil CR, Pexeva), and fluvoxamine (Luvox CR). Depression may be caused by an imbalance between serotonin and other neurotransmitters. Experts believe that drugs such as Zoloft restore the chemical balance among neurotransmitters in the brain. SSRIs block the reuptake of serotonin, thus changing the level of serotonin in the brain. A serotonin balance is reached between attachment to the nearby nerves and reuptake.

Wellbutrin (bupropion) is an antidepressant used to treat major depression and seasonal affective disorder. Off-label uses for Wellbutrin include posttraumatic stress disorder (PTSD), anxiety, attention deficit hyperactivity disorder (ADHD), social phobia, and nerve pain (neuropathic pain). The Zyban brand of bupropion is prescribed for smoking cessation. Many experts believe depression is caused by an imbalance among the amounts of neurotransmitters that are released. Wellbutrin works by inhibiting the reuptake of dopamine, serotonin, and norepinephrine — an action that results in more dopamine, serotonin, and norepinephrine to transmit messages to other nerves. Wellbutrin is unlike other antidepressants in that its major effect is on dopamine, an effect not shared by the selective serotonin reuptake inhibitors (SSRIs) or the tricyclic antidepressants (TCAs).


Depression is a(n) __________ . See Answer

What are the side effects of Zoloft and Wellbutrin?



  • As demonstrated in short-term studies, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Zoloft or any other antidepressant in a child or adolescent must balance this risk with the clinical need for the antidepressant. Patients who begin therapy should be closely observed for clinical worsening, suicidal thoughts, or unusual changes in behavior.

The most common side effects of Zoloft are:

Possible serious side effects of Zoloft include:

Important side effects are irregular heartbeats, allergic reactions and activation of mania in patients with bipolar disorder.

If Zoloft is discontinued abruptly, some patients experience side effects such as:

A gradual dose reduction of Zoloft is recommended when therapy is discontinued.



Four of every 1000 persons who receive Wellbutrin in doses less than 450 mg/day experience seizures. When doses exceed 450 mg/day, the risk increases tenfold. Other risk factors for seizures include past injury to the head and medications that can lower the threshold for seizures. (See drug interactions.)

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Wellbutrin or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who begin therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

The most common side effects associated with Wellbutrin include:

In some people, the agitation or insomnia is most marked shortly after starting therapy.

Less common side effects include:

More serious side effects include:

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What is the dosage of Zoloft vs. Wellbutrin?


  • The recommended dose of Zoloft is 25 to 200 mg once daily. Treatment of depression, OCD, panic disorder, PTSD, and social anxiety disorder is initiated at 25 to 50 mg once daily. Doses are increased at weekly intervals until the desired response is seen.
  • The recommended dose for PMDD is 50 to 150 mg every day of the menstrual cycle or for 14 days before menstruation.
  • Zoloft may be taken with or without food.


  • Wellbutrin immediate release tablets are usually given in one, two or three daily doses. For immediate-release tablets, no single dose should exceed 150 mg and each dose should be separated by 6 hours.
  • For depression, the recommended dose of immediate-release tablets is 100 mg 3 times daily (300 mg/day); maximum dose is 450 mg daily. The initial dose is 100 mg twice daily. The dose may be increased to 100 mg 3 times daily after three days and 150 mg 3 times daily after several weeks if the initial response is not adequate.
  • The initial dose of sustained-release tablets is 150 mg daily; target dose is 150 mg twice daily; maximum dose is 200 mg twice daily.
  • The initial dose of extended-release tablets is 150 mg daily; target dose is 300 mg daily; maximum dose is 450 mg daily. Extended release tablets are administered once daily.
  • Some patients with depression may be switched from bupropion hydrochloride (Wellbutrin, for example) to bupropion hydrobromide (Aplenzin) while others may need doses higher than those listed above. Your doctor should determine the correct dose of these medications for you.
  • When used for smoking cessation, bupropion (Zyban) usually is started as 150 mg once daily for three days, and then the dose is increased to 150 mg twice daily for 7 to 12 weeks if the patient tolerates the starting dose. Smoking is discontinued two weeks after starting bupropion therapy.
  • The dose for seasonal affective disorder is 150 mg once daily up to 300 mg daily using bupropion hydrochloride extended release tablets (for example, Wellbutrin XL). Alternatively, treatment may be started with 174 mg bupropion hydrobromide (Aplenzin) daily and increased to a target dose of 348 mg/day. Start treatment in the autumn prior to onset of seasonal depressive symptoms and continue through the winter season.


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What drugs interact with Zoloft and Wellbutrin?


All SSRIs, including Zoloft, should not be taken with any of the monoamine oxidase inhibitor (MAOI) class of antidepressants, for example

  • isocarboxazid (Marplan),
  • phenelzine (Nardil),
  • tranylcypromine (Parnate),
  • selegiline (Eldepryl, Emsam, Elazar), and
  • procarbazine (Matulane).

Other drugs that inhibit monoamine oxidase include

Such combinations may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. (A period of 14 days without treatment should lapse when switching between Zoloft and MAOIs.) Similar reactions occur when Zoloft is combined with other drugs — for example, tryptophan, St. John’s wort, meperidine (Demerol, Meperitab), tramadol (ConZip, Synapryn FusePaq, Ultram) — that increase serotonin in the brain.

Cimetidine (Cimetidine Acid Reducer, Tagamet HB ) may increase the levels in blood of Zoloft by reducing the elimination of Zoloft by the liver. Increased levels of Zoloft may lead to more side effects.

Zoloft increases the blood level of pimozide (Orap) by 40%. High levels of pimozide can affect electrical conduction in the heart and lead to sudden death. Therefore, patients should not receive treatment with both pimozide and Zoloft.

Through unknown mechanisms, Zoloft may increase the blood thinning action of warfarin (Coumadin, Jantoven). The effect of warfarin should be monitored when Zoloft is started or stopped.


  • Wellbutrin should be used cautiously in patients receiving drugs that reduce the threshold for seizures. Such drugs include prochlorperazine (Compazine), chlorpromazine (Thorazine), and other antipsychotic medications of the phenothiazine class. Additionally, persons who are withdrawing from benzodiazepines [for example, diazepam (Valium), alprazolam (Xanax)] are at increased risk for seizures.
  • Carbamazepine (Tegretol) may reduce the effect of Wellbutrin by reducing the blood concentration of Wellbutrin. Monamine oxidase inhibitors should not be combined with Wellbutrin because of the risk of severe reactions. At least 14 days should elapse between discontinuation of an MAOI and initiation of Wellbutrin. Wellbutrin may affect the action of warfarin (Coumadin).
  • Ritonavir (Norvir) may increase the breakdown and elimination of Wellbutrin. In some studies ritonavir reduced the concentration of Wellbutrin in the body by 22% to 66%.

Are Zoloft and Wellbutrin safe to use while pregnant or breastfeeding?


Use of Zoloft during the third trimester of pregnancy may lead to adverse effects in the newborn.

Use of Zoloft by nursing mothers has not been adequately evaluated.


There are no adequate studies of Wellbutrin in pregnant women. In one study, there was no difference between Wellbutrin and other antidepressants in the occurrence of birth defects. Wellbutrin should only be used in pregnancy if the benefit outweighs the potential risk.

Wellbutrin is secreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, discontinue use of Wellbutrin or discontinue breastfeeding.

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Medically Reviewed on 6/27/2019



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