Wellbutrin vs. Sertraline
See how Wellbutrin and Sertraline compare on approved uses, dosing, side effects, and cost.
Key Takeaways
Wellbutrin is an NDRI antidepressant with low rates of sexual side effects and weight gain, while sertraline is an SSRI also approved for OCD, PTSD, and panic disorder.
Wellbutrin needs two or three doses a day, while sertraline is taken once daily from the start.
Generic sertraline typically costs far less per month than brand-name Wellbutrin, which can be a deciding factor without insurance.
Wellbutrin vs. Sertraline Drug Summary
Wellbutrin
Wellbutrin (bupropion) is an aminoketone antidepressant that works differently from SSRIs, raising norepinephrine and dopamine instead of serotonin. It is FDA approved for major depressive disorder and taken as an immediate-release tablet, usually two or three times a day. Some clinicians also prescribe it off-label for ADHD or to counter sexual side effects caused by other antidepressants.
Sertraline
Sertraline (Zoloft) is an SSRI that increases serotonin levels in the brain to help regulate mood. It is FDA approved for major depressive disorder as well as OCD, panic disorder, PTSD, social anxiety disorder, and premenstrual dysphoric disorder. It comes as a once-daily tablet, typically started at a low dose and increased gradually if needed.
Wellbutrin vs. Sertraline Side Effects
Wellbutrin
Sertraline
Wellbutrin vs. Sertraline Dosage
Wellbutrin
Sertraline
| 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 | 50 mg once daily | At the start |
| Maximum dose | 200 mg once daily | If needed |
| Dose changes | 3 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 |
Sertraline
| STAGE | DOSE | WHEN |
| Starting dose | 50 mg once daily | At the start |
| Maximum dose | 200 mg once daily | If needed |
| Dose changes | 3 increases | As tolerated |
Wellbutrin vs. Sertraline Indications
Wellbutrin
Wellbutrin is FDA approved only for major depressive disorder in adults. It is not approved for anxiety, though clinicians sometimes prescribe it off-label for ADHD, as an add-on for bipolar depression, or to offset sexual side effects from other antidepressants.
FDA approved: major depressive disorder (MDD)
Off-label: ADHD in adults and children
Off-label: bipolar depression, used as an add-on
Off-label: sexual dysfunction from other antidepressants
Off-label: weight management
Sertraline
Sertraline is FDA approved for major depressive disorder and five additional conditions: OCD, panic disorder, PTSD, social anxiety disorder, and PMDD. This broad approval makes it a common first choice when depression overlaps with an anxiety-related condition.
FDA approved: major depressive disorder (MDD)
FDA approved: obsessive-compulsive disorder (OCD)
FDA approved: panic disorder
FDA approved: PTSD and social anxiety disorder
FDA approved: premenstrual dysphoric disorder (PMDD)
Wellbutrin vs. Sertraline Pros and Cons
Wellbutrin
Wellbutrin works through a different mechanism than SSRIs, which is why it tends to cause less sexual dysfunction and less weight gain. It carries a dose-related seizure risk and is not an option for people with a seizure disorder or an eating disorder history. The immediate-release form also requires multiple daily doses.
Pros
Low risk of sexual side effects and weight gain unlike SSRIs
Non-sedating, may help with low energy and fatigue
Same active ingredient sold as Zyban for smoking cessation off-label
Cons
Requires two or three doses a day to stay effective
Carries a seizure risk; contraindicated with seizure or eating disorders
Not FDA approved for anxiety disorders despite off-label use
List price runs far above generic sertraline's cost
Sertraline
Sertraline is one of the most widely prescribed SSRIs, with FDA approval covering several anxiety-related conditions beyond depression. It is taken once a day and has decades of safety data, though sexual side effects and GI symptoms are common. As a well-established generic, coverage and cost are rarely a barrier.
Pros
FDA approved for OCD, panic disorder, PTSD, and social anxiety
Once-daily dosing from the very first dose
Generic version costs far less than Wellbutrin's list price
Cons
Ejaculation failure and other sexual side effects are common
Diarrhea and other GI symptoms are frequent early on
Can cause weight gain over time, unlike weight-neutral bupropion
Needs several titration steps over weeks to reach full dose
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