Prozac vs Zoloft: fluoxetine and sertraline compared
Prozac (fluoxetine) and Zoloft (sertraline) are SSRI antidepressants, both available as generics. The main differences are how long fluoxetine stays in the body, the interactions each carries, and the conditions each is approved for.
Updated October 15, 2026
At a glance
- Approved uses
- Prozac
- Depression, OCD, panic disorder, bulimia, PMDD
- Zoloft
- Depression, OCD, panic disorder, PTSD, social anxiety disorder, PMDD
- Time in the body
- Prozac
- Very long, with an active metabolite lasting weeks
- Zoloft
- About a day
- Drug interactions
- Prozac
- More, through the liver enzyme CYP2D6
- Zoloft
- Fewer
- Generic available
- Prozac
- Yes, as capsules, tablets and liquid
- Zoloft
- Yes, as tablets and liquid
Prozac fluoxetine | Zoloft sertraline | |
|---|---|---|
| Approved uses | Depression, OCD, panic disorder, bulimia, PMDD | Depression, OCD, panic disorder, PTSD, social anxiety disorder, PMDD |
| Time in the body | Very long, with an active metabolite lasting weeks | About a day |
| Drug interactions | More, through the liver enzyme CYP2D6 | Fewer |
| Generic available | Yes, as capsules, tablets and liquid | Yes, as tablets and liquid |
The long half-life cuts both ways
Fluoxetine lingers for weeks, so missed doses matter little and stopping rarely causes the discontinuation symptoms that shorter-acting SSRIs can. The same property means side effects and interactions also take weeks to clear after stopping, and switching to some other medicines needs a longer gap. Sertraline clears within days, which makes adjustments quicker.
Side effects and interactions
Fluoxetine more often feels activating, with restlessness or trouble sleeping, and is usually taken in the morning; sertraline more often upsets the stomach. Fluoxetine strongly blocks the liver enzyme CYP2D6, which affects drugs such as tamoxifen, some beta blockers and some antipsychotics. Both carry the boxed warning about suicidal thoughts in people under 25, can cause sexual side effects, and raise bleeding risk with blood thinners and anti-inflammatories.
Cost
Both are available as generics, and fluoxetine comes as capsules, tablets and a liquid, so ask for quotes on the form your prescriber is comfortable with. Each pharmacy sets its own cash price, and quotes can differ between pharmacies and between thirty-day and ninety-day fills.
Who might get one rather than the other
Fluoxetine is approved for depression in children from age 8 and is often chosen when missed doses are likely or when someone has had discontinuation symptoms on another SSRI. Sertraline is often preferred during breastfeeding, for PTSD and social anxiety where it is approved, and when other medicines interact with fluoxetine.
Questions for your prescriber
- Which is approved for my condition?
- Do any of my medicines interact with fluoxetine?
- If I switch from one to the other, how should it be done?
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Sources
- DailyMed, FDA-approved prescribing information
- MedlinePlus drug information (National Library of Medicine)
- FDA Orange Book (approved generics and therapeutic equivalence)
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.