Two medicines, side by side
Amitriptyline vs duloxetine
Amitriptyline and duloxetine are both labeled for depression. Drugs@FDA records approvals of amitriptyline since 1961 and of duloxetine since 2004. Pharmacies paid $0.03 per amitriptyline HCl 10 mg tablet and $0.102 per duloxetine HCl DR 30 mg capsule (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 duloxetine a serotonin and norepinephrine reuptake inhibitor.
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026); the duloxetine FDA label on DailyMed (effective May 14, 2024).
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 duloxetine record
Duloxetine (Cymbalta) · label of May 14, 2024
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: indicationsDRIZALMA SPRINKLE is indicated for the treatment of: • Major Depressive Disorder in adults • Generalized Anxiety Disorder in adults and pediatric patients 7 years of age and older • Diabetic Peripheral Neuropathy in adults • Fibromyalgia in adults • Chronic Musculoskeletal Pain in adults Additional pediatric use information is approved for Eli Lilly and Company, Inc.’s CYMBALTA (duloxetine delayed-release capsules). […]
On the market
- Earliest approval on file
- August 3, 2004
- Generic labelers
- 45 labelers
- Pharmacy cost
- $0.102 per capsule
Supply and safety
- Shortage
- No current entry
- Recalls
- 56
Source: FDA drug labels via openFDA (Amitriptyline label of September 8, 2026, Duloxetine label of May 14, 2024); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do amitriptyline and duloxetine differ on the record?
In FDA's classes, amitriptyline is a tricyclic antidepressant and duloxetine a serotonin and norepinephrine 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.”; Duloxetine, “Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation …”
Both labels carry a boxed warning; the records quote them.
Generics: amitriptyline since 1976; duloxetine since 2013 (Drugs@FDA).
| Amitriptyline | Duloxetine | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety, Nerve pain and fibromyalgia, Pain |
| Pharmacologic class | Tricyclic Antidepressant | Serotonin and Norepinephrine 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. | Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic … |
| Half-life (label) | n/a | Mean terminal half-life was 12.4 hours (range 7.8 to 22.2 hour) in subjects receiving a single dose DRIZALMA SPRINKLE. |
| Earliest approval on file (Drugs@FDA) | April 7, 1961 | August 3, 2004 |
| First generic approved | November 16, 1976 | December 11, 2013 |
| Generic labelers (NDC) | 34 labelers | 45 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.03 per tablet (Amitriptyline HCl 10 mg tablet) | $0.102 per capsule (Duloxetine HCl DR 30 mg capsule) |
| 12-month price change | -19% | +31% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 2 | 56 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 17,441 | 69,298 |
| 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?
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.
Duloxetine label, drug interactionsExamples Selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, intravenous methylene blue Other Serotonergic Drugs Clinical Impact Concomitant use of duloxetine with other serotonergic drugs increases the risk of serotonin syndrome.
Source: FDA drug labels via openFDA
What next?
- Alternatives to amitriptyline
- every medicine labeled for the same conditions