Zoloft vs. Wellbutrin
See how Zoloft and Wellbutrin compare on approved uses, dosing, side effects, and cost.
Key Takeaways
Zoloft is an SSRI FDA-approved for depression, OCD, panic disorder, PTSD, PMDD, and social anxiety, while Wellbutrin's FDA approval covers only major depressive disorder.
Zoloft more often causes sexual side effects and drowsiness, while Wellbutrin is more likely to cause agitation, dry mouth, and a dose-related seizure risk.
Doctors sometimes add Wellbutrin to Zoloft off-label to offset SSRI-related sexual side effects, but this combination should only be done under medical supervision.
Zoloft vs. Wellbutrin Drug Summary
Zoloft
Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, OCD, panic disorder, PTSD, PMDD, and social anxiety disorder. It comes as a tablet or oral solution, usually started at 25 mg or 50 mg once a day.
Wellbutrin
Wellbutrin (bupropion) is an aminoketone antidepressant that raises norepinephrine and dopamine instead of serotonin. Its FDA approval covers only major depressive disorder, and it's taken as an immediate-release tablet two to three times a day.
Zoloft vs. Wellbutrin Side Effects
Zoloft
Wellbutrin
Zoloft vs. Wellbutrin Dosage
Zoloft
Wellbutrin
| STAGE | DOSE | WHEN |
| Starting dose | 25-50 mg/day | Day 1 |
| Maximum dose | Up to 200 mg/day | If needed |
| Dose changes | 2 increases | As tolerated |
| STAGE | DOSE | WHEN |
| Starting dose | 200 mg/day (100 mg BID) | Days 1-3 |
| Maximum dose | 450 mg/day (150 mg TID) | If needed |
| Dose changes | 2 increases | Every 3 days |
Zoloft
| STAGE | DOSE | WHEN |
| Starting dose | 25-50 mg/day | Day 1 |
| Maximum dose | Up to 200 mg/day | If needed |
| Dose changes | 2 increases | As tolerated |
Wellbutrin
| STAGE | DOSE | WHEN |
| Starting dose | 200 mg/day (100 mg BID) | Days 1-3 |
| Maximum dose | 450 mg/day (150 mg TID) | If needed |
| Dose changes | 2 increases | Every 3 days |
Zoloft vs. Wellbutrin Indications
Zoloft
Zoloft is FDA-approved for a wide range of psychiatric conditions beyond depression. Doctors often reach for it first because of this broad label and decades of safety data.
Major depressive disorder (MDD)
Obsessive-compulsive disorder (OCD)
Panic disorder
Post-traumatic stress disorder (PTSD)
Social anxiety disorder and PMDD
Wellbutrin
Wellbutrin's FDA approval is narrower, covering only major depressive disorder. Clinicians frequently prescribe it off-label for other conditions, though those uses are not FDA-approved.
Major depressive disorder (MDD) - FDA-approved
ADHD in adults and children (off-label)
Bipolar depression as an add-on (off-label)
Antidepressant-induced sexual dysfunction (off-label)
Obesity or weight management (off-label)
Zoloft vs. Wellbutrin Pros and Cons
Zoloft
Zoloft's broad FDA approval and long track record make it a common first choice for depression and several anxiety-related conditions. Generic sertraline is inexpensive, though sexual side effects and initial jitteriness are common trade-offs.
Pros
FDA-approved for six psychiatric conditions, not just depression
Approved for OCD in children as young as 6
No seizure risk, so it fits more medical histories
Generic sertraline is low-cost and widely covered
Cons
Sexual side effects, including ejaculation problems in up to 14% of men
Boxed warning for suicidal thoughts in patients under 25
Stopping abruptly can cause dizziness and 'brain zaps'
Can cause either drowsiness or insomnia depending on the person
Wellbutrin
Wellbutrin works on dopamine and norepinephrine rather than serotonin, so it avoids many of the sexual side effects and weight gain linked to SSRIs like Zoloft. Its FDA approval is limited to depression, and it carries a dose-related seizure risk that Zoloft does not.
Pros
Much lower rates of sexual side effects than SSRIs like Zoloft
Less likely to cause weight gain, may cause modest weight loss
Non-sedating, can improve energy and focus
Same active ingredient as Zyban, an FDA-approved smoking cessation aid
Cons
FDA-approved only for depression, not anxiety, OCD, or PTSD
Seizure risk rises with dose; contraindicated in seizure disorders
Not recommended for people with a history of eating disorders
Can worsen anxiety or cause agitation and insomnia
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