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
Fluoxetine
Wellbutrin vs. Fluoxetine Dosage
Wellbutrin
Fluoxetine
| 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 |
| 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
| 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
| 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
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