Two medicines, side by side
Fluoxetine vs sertraline
Fluoxetine and sertraline are both labeled for depression and anxiety. Drugs@FDA records approvals of fluoxetine since 1987 and of sertraline since 1991. Pharmacies paid $0.0519 per fluoxetine HCl 40 mg capsule and $0.0507 per sertraline HCl 100 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. How each works, in its label's words: Fluoxetine, “Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.”; Sertraline, “Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT).”
Check it at the source: the fluoxetine FDA label on DailyMed (effective January 8, 2026); the sertraline FDA label on DailyMed (effective August 8, 2023).
Highlights of the fluoxetine record
Fluoxetine (Prozac) · label of January 8, 2026
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions ( 5.1 )].
Used for
From the label: indicationsPROZAC ® is indicated for the treatment of: Acute and maintenance treatment of Major Depressive Disorder [see Clinical Studies ( 14.1 )]. Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [see Clinical Studies ( 14.2 )]. […]
On the market
- Earliest approval on file
- December 29, 1987
- Generic labelers
- 58 labelers
- Pharmacy cost
- $0.0519 per capsule
Supply and safety
- Shortage
- No current entry
- Recalls
- 9
Highlights of the sertraline record
Sertraline (Zoloft) · label of August 8, 2023
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [See Warnings and Precautions (5.1) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning.
Used for
From the label: indicationsZOLOFT is indicated for the treatment of the following [See Clinical Studies (14) ]: • Major depressive disorder (MDD) • Obsessive-compulsive disorder (OCD) • Panic disorder (PD) • Posttraumatic stress disorder (PTSD) • Social anxiety disorder (SAD) • Premenstrual dysphoric disorder (PMDD) ZOLOFT is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of ( 1 ): • Major depressive disorder […]
On the market
- Earliest approval on file
- December 30, 1991
- Generic labelers
- 47 labelers
- Pharmacy cost
- $0.0507 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 3
Source: FDA drug labels via openFDA (Fluoxetine label of January 8, 2026, Sertraline label of August 8, 2023); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do fluoxetine and sertraline differ on the record?
How each works, in its label's words: Fluoxetine, “Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.”; Sertraline, “Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT).”
Both are in FDA's class serotonin reuptake inhibitors.
Half-life, in each label's words: Fluoxetine, “Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days.”; Sertraline, “The average terminal elimination half-life of plasma sertraline is about 26 hours.”
Both labels carry a boxed warning; the records quote them.
Generics: fluoxetine since 2001; sertraline since 2006 (Drugs@FDA).
| Fluoxetine | Sertraline | |
|---|---|---|
| Labeled for | Depression, Anxiety, Bipolar disorder | Depression, Anxiety |
| Pharmacologic class | Serotonin Reuptake Inhibitor | Serotonin Reuptake Inhibitor |
| How it works (label) | Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. | Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT). |
| Half-life (label) | Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days. | The average terminal elimination half-life of plasma sertraline is about 26 hours. |
| Earliest approval on file (Drugs@FDA) | December 29, 1987 | December 30, 1991 |
| First generic approved | August 2, 2001 | June 30, 2006 |
| Generic labelers (NDC) | 58 labelers | 47 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.0519 per capsule (Fluoxetine HCl 40 mg capsule) | $0.0507 per tablet (Sertraline HCl 100 mg tablet) |
| 12-month price change | -20% | -3% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 9 | 3 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 131,827 | 218,311 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
What do the labels say about using others of their kind?
Fluoxetine label, warnings and precautionsSerotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents.
Sertraline label, warnings and precautionsIncreased risk when co-administered with other serotonergic agents, but also when taken alone.
Source: FDA drug labels via openFDA
What next?
- Alternatives to fluoxetine
- every medicine labeled for the same conditions