Sertraline vs. Fluoxetine

See how Sertraline and Fluoxetine compare on approved uses, dosing, side effects, and cost.

Key Takeaways

  • Sertraline and fluoxetine are both SSRIs, but sertraline is FDA-approved for panic disorder, PTSD, social anxiety, and PMDD, while fluoxetine covers bulimia nervosa and depression in children as young as 8.

  • Fluoxetine's long-acting metabolite allows a once-weekly maintenance dose and causes fewer withdrawal symptoms if a dose is missed, while sertraline requires daily dosing throughout treatment.

  • Both carry a boxed warning for increased suicidal thoughts in people under 25 and are widely available as inexpensive generic medications.

Sertraline vs. Fluoxetine Drug Summary

Sertraline

Sertraline is a selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, OCD, panic disorder, PTSD, social anxiety disorder, and premenstrual dysphoric disorder. It comes as a tablet, capsule, or oral solution taken once a day, usually starting at 50 mg.

Fluoxetine

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, OCD, bulimia nervosa, and panic disorder, plus bipolar and treatment-resistant depression when combined with olanzapine. It comes as a capsule, tablet, or oral solution, usually starting at 20 mg once daily, with a once-weekly maintenance option.

Sertraline vs. Fluoxetine Side Effects

Sertraline

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

Fluoxetine

Most common
nausea (up to 21%)
insomnia (up to 33%)
diarrhea (up to 12%)
headache (up to 21%)

Sertraline vs. Fluoxetine Dosage

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

Fluoxetine

Dosage
Dosage Table
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

Sertraline vs. Fluoxetine Indications

Sertraline

Sertraline holds FDA approval for six separate conditions, more than most other SSRIs, spanning depression and several anxiety-related disorders. Doctors also prescribe it off-label for generalized anxiety disorder and body dysmorphic disorder.

  • Major depressive disorder (MDD)

  • Obsessive-compulsive disorder, ages 6+

  • Panic disorder and PTSD

  • Social anxiety disorder

  • Premenstrual dysphoric disorder (PMDD)

Fluoxetine

Fluoxetine was the first SSRI approved in the United States and covers depression, OCD, and bulimia nervosa, plus pediatric depression down to age 8. It's also approved in combination with olanzapine for bipolar depression and treatment-resistant depression.

  • Major depressive disorder, including ages 8+

  • Obsessive-compulsive disorder, ages 7+

  • Bulimia nervosa and panic disorder

  • Bipolar depression (with olanzapine)

  • Treatment-resistant depression (with olanzapine)

Sertraline vs. Fluoxetine Pros and Cons

Sertraline

Sertraline covers more FDA-approved anxiety disorders than fluoxetine, making it a common first choice when anxiety and depression overlap. It is a generic, insurance-friendly medication that requires a daily dosing routine.

Pros

  • FDA-approved for PTSD and panic disorder

  • FDA-approved for social anxiety disorder

  • Shorter half-life may allow faster dose adjustments

Cons

  • Not FDA-approved for pediatric depression

  • Higher rate of diarrhea in trials

  • No once-weekly dosing option

Fluoxetine

Fluoxetine's long-acting metabolite means missed doses cause fewer withdrawal symptoms than most SSRIs, and it offers a once-weekly maintenance option after stabilization. It is also approved for younger children with depression than sertraline.

Pros

  • FDA-approved for pediatric depression from age 8

  • Once-weekly maintenance dosing option

  • Lower risk of discontinuation symptoms from missed doses

Cons

  • Not FDA-approved for PTSD or social anxiety

  • Higher rate of insomnia than sertraline in trials

  • Long half-life can delay resolution of side effects

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