Wellbutrin vs. Fluoxetine

See how Wellbutrin and Fluoxetine compare on approved uses, dosing, side effects, and cost.

Key Takeaways

  • Wellbutrin is a norepinephrine-dopamine reuptake inhibitor with lower rates of sexual side effects and weight gain than SSRIs, while fluoxetine is an SSRI with decades of generic availability and broader FDA-approved uses.

  • Wellbutrin carries a dose-related seizure risk and is contraindicated in people with seizure disorders or eating disorders, while fluoxetine's main risks are serotonin syndrome and interactions with other serotonergic drugs.

  • Fluoxetine is FDA-approved for OCD, panic disorder, and bulimia in addition to depression, while Wellbutrin is only FDA-approved for major depressive disorder despite common off-label use for ADHD.

Wellbutrin vs. Fluoxetine Drug Summary

Wellbutrin

Wellbutrin (bupropion) is an aminoketone antidepressant that works by increasing norepinephrine and dopamine activity rather than serotonin. It is FDA-approved for major depressive disorder and is taken as an oral immediate-release tablet, usually two to three times a day.

Fluoxetine

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin activity in the brain and has been used since 1987. It is FDA-approved for depression, OCD, panic disorder, and bulimia, and is taken once daily as a capsule, tablet, or liquid, with a once-weekly maintenance option.

Wellbutrin vs. Fluoxetine Side Effects

Wellbutrin

Most common
headache (≥5%)
insomnia (≥5%)
nausea (≥5%)
dry mouth (≥5%)

Fluoxetine

Most common
headache (up to 21%)
insomnia (up to 33%)
nausea (up to 21%)
somnolence (up to 13%)

Wellbutrin vs. Fluoxetine Dosage

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

Fluoxetine

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 10 mg once daily Week 1
Maximum dose 90 mg once weekly If needed
Dose changes 4 increases Every week

Wellbutrin vs. Fluoxetine Indications

Wellbutrin

Wellbutrin is FDA-approved only for major depressive disorder, but its distinct mechanism drives frequent off-label use for other conditions. It avoids the sexual side effects and sedation common with SSRIs, which is often why clinicians choose it instead.

  • Major depressive disorder (FDA-approved)

  • ADHD in adults and children (off-label)

  • Bipolar depression as an adjunct (off-label)

  • Antidepressant-induced sexual dysfunction (off-label)

  • Obesity or weight management (off-label)

Fluoxetine

Fluoxetine has one of the broadest FDA approval lists among antidepressants, covering depression, OCD, panic disorder, and bulimia nervosa. It is also approved in combination with olanzapine for bipolar depression and treatment-resistant depression.

  • Major depressive disorder, ages 8 and up

  • Obsessive-compulsive disorder, ages 7 and up

  • Panic disorder in adults

  • Bulimia nervosa in adults

  • Bipolar depression with olanzapine (combo)

Wellbutrin vs. Fluoxetine Pros and Cons

Wellbutrin

Wellbutrin stands apart from SSRIs by targeting norepinephrine and dopamine instead of serotonin, which generally means fewer sexual side effects and less weight gain. It costs more out of pocket than generic fluoxetine and carries a seizure risk that limits its use in some patients.

Pros

  • Lower rates of sexual side effects than SSRIs

  • Less likely to cause weight gain

  • Non-sedating, may improve energy and focus

  • Commonly used off-label for ADHD

Cons

  • Seizure risk; contraindicated with seizure history

  • Not approved for anxiety disorders

  • Contraindicated with bulimia or anorexia history

  • Roughly $500 to $900 per month without insurance

Fluoxetine

Fluoxetine has the longest track record of any SSRI and the broadest set of FDA-approved uses, from OCD to bulimia to panic disorder. Its low cost as a decades-old generic makes it accessible, though it carries the class-wide risk of sexual side effects and GI upset.

Pros

  • FDA-approved for OCD, panic disorder, and bulimia

  • Long half-life makes missed doses more forgiving

  • Once-weekly maintenance dosing option available

  • Roughly $25 to $60 per month as a generic

Cons

  • Sexual side effects common with long-term use

  • GI side effects like nausea and diarrhea are common

  • Risk of serotonin syndrome with other serotonergic drugs

  • Higher rates of insomnia than many antidepressants

Common Symptoms and Related Diseases You Can Explore

Explore a range of common symptoms the Doctronic Symptom Checker can help you understand.