Two medicines, side by side
Amitriptyline vs sertraline
Amitriptyline and sertraline are both labeled for depression. Drugs@FDA records approvals of amitriptyline since 1961 and of sertraline since 1991. Pharmacies paid $0.03 per amitriptyline HCl 10 mg tablet 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. In FDA's classes, amitriptyline is a tricyclic antidepressant and sertraline a serotonin reuptake inhibitor.
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026); the sertraline FDA label on DailyMed (effective August 8, 2023).
Highlights of the amitriptyline record
Amitriptyline (Elavil) · label of September 8, 2026
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Used for
From the label: indicationsFor the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
On the market
- Earliest approval on file
- April 7, 1961
- Generic labelers
- 34 labelers
- Pharmacy cost
- $0.03 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 2
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 (Amitriptyline label of September 8, 2026, Sertraline label of August 8, 2023); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do amitriptyline and sertraline differ on the record?
In FDA's classes, amitriptyline is a tricyclic antidepressant and sertraline a serotonin reuptake inhibitor.
How each works, in its label's words: Amitriptyline, “It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.”; Sertraline, “Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT).”
Both labels carry a boxed warning; the records quote them.
Generics: amitriptyline since 1976; sertraline since 2006 (Drugs@FDA).
| Amitriptyline | Sertraline | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety |
| Pharmacologic class | Tricyclic Antidepressant | Serotonin Reuptake Inhibitor |
| How it works (label) | in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system. | Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT). |
| Half-life (label) | n/a | The average terminal elimination half-life of plasma sertraline is about 26 hours. |
| Earliest approval on file (Drugs@FDA) | April 7, 1961 | December 30, 1991 |
| First generic approved | November 16, 1976 | June 30, 2006 |
| Generic labelers (NDC) | 34 labelers | 47 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.03 per tablet (Amitriptyline HCl 10 mg tablet) | $0.0507 per tablet (Sertraline HCl 100 mg tablet) |
| 12-month price change | -19% | -3% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 2 | 3 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 17,441 | 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)
Do their labels mention each other?
Amitriptyline label, drug interactionsWhile all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
Source: FDA drug labels via openFDA
What do the labels say about using others of their kind?
Amitriptyline label, warningsIf concomitant use of amitriptyline hydrochloride with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
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 amitriptyline
- every medicine labeled for the same conditions