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

Most common
Nausea (up to 26%)
Diarrhea (up to 20%)
Insomnia (up to 20%)
Dry mouth (up to 14%)

Wellbutrin

Most common
Headache/migraine (up to 34%)
Nausea/vomiting (up to 18%)
Dry mouth (up to 17%)
Constipation (up to 10%)

Zoloft vs. Wellbutrin Dosage

Zoloft

Dosage
Dosage Table
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

Dosage
Dosage Table
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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