Wellbutrin vs Zoloft: antidepressants compared
Wellbutrin (bupropion) and Zoloft (sertraline) are both widely used antidepressants, but they act on different brain chemicals and suit different people. Zoloft also treats anxiety disorders; Wellbutrin is less likely to cause sexual side effects or weight gain and also helps people stop smoking.
Updated October 4, 2026
At a glance
- How it works
- Wellbutrin
- Affects norepinephrine and dopamine
- Zoloft
- Affects serotonin
- Approved for
- Wellbutrin
- Depression, seasonal affective disorder, and stopping smoking (as Zyban)
- Zoloft
- Depression, panic disorder, OCD, PTSD, social anxiety disorder, PMDD
- Sexual side effects
- Wellbutrin
- Less common
- Zoloft
- More common
- Weight
- Wellbutrin
- Usually neutral or slight loss
- Zoloft
- Can increase over time
- Generic
- Wellbutrin
- Yes
- Zoloft
- Yes
Wellbutrin bupropion | Zoloft sertraline, an SSRI | |
|---|---|---|
| How it works | Affects norepinephrine and dopamine | Affects serotonin |
| Approved for | Depression, seasonal affective disorder, and stopping smoking (as Zyban) | Depression, panic disorder, OCD, PTSD, social anxiety disorder, PMDD |
| Sexual side effects | Less common | More common |
| Weight | Usually neutral or slight loss | Can increase over time |
| Generic | Yes | Yes |
Anxiety and energy
Sertraline treats several anxiety disorders as well as depression, which makes it a common first choice when the two occur together. Bupropion is not approved for anxiety and can cause jitteriness or trouble sleeping, though it can suit people whose depression brings low energy. Some people take both, under their prescriber’s direction, to balance effects.
Safety differences
Bupropion raises the risk of seizures at higher doses, so it is not used in people with seizure disorders or eating disorders such as bulimia, and a missed dose should never be doubled. Sertraline carries the risks common to serotonin medicines, including serotonin syndrome with other serotonin-affecting drugs and more bleeding with blood thinners. Both carry a warning about suicidal thoughts in young people, and neither should be stopped suddenly without advice.
Cost
Both are generics with modest cash prices. Extended-release bupropion and some sertraline forms can cost more, so ask your pharmacy for a quote on the exact form you take.
Starting and stopping
Both take several weeks to reach their full effect, so prescribers usually review progress after four to six weeks before changing course. Sertraline is often started low and increased; bupropion doses are increased in steps to limit side effects and seizure risk. Stopping sertraline suddenly can cause discontinuation symptoms such as dizziness and irritability, so it is tapered, and bupropion is reduced only as your prescriber advises.
Questions for your prescriber
- Which suits my symptoms, including any anxiety, sleep or energy problems?
- How much do sexual side effects or weight changes matter in my choice?
- How long before I can tell whether it is working?
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Sources
Written by the Script Unlock editorial team from the sources above. It is general information, not advice for you or your pet; your prescriber decides which medicine is right.
Script Unlock is a marketplace that lets licensed pharmacies quote a cash price on your prescription. It does not prescribe, dispense or sell medication, does not process patient payments, and does not give medical advice. Always follow the instructions of your prescriber and pharmacist and read the medication guide supplied with your medicine.