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

Most common
headache/migraine (up to 26%)
dry mouth (up to 17%)
nausea/vomiting (up to 13%)
insomnia (up to 11%)

Sertraline

Most common
nausea (up to 26%)
insomnia (up to 21%)
diarrhea (up to 20%)
ejaculation failure (up to 14%)

Wellbutrin vs. Sertraline 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

Sertraline

Dosage
Dosage Table
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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