Two medicines, side by side
Amitriptyline vs paroxetine
Amitriptyline and paroxetine are both labeled for depression. Drugs@FDA records approvals of amitriptyline since 1961 and of paroxetine since 1992. Pharmacies paid $0.03 per amitriptyline HCl 10 mg tablet and $0.0611 per paroxetine HCl 20 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 paroxetine a serotonin reuptake inhibitor.
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026); the paroxetine FDA label on DailyMed (effective February 12, 2026).
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 paroxetine record
Paroxetine (Paxil) · label of February 12, 2026
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors 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) ]. Paroxetine tablets are not approved for use in pediatric patients [see Use in Specific Populations (8.4) ].
Used for
From the label: indicationsParoxetine tablets are indicated in adults for the treatment of: • Major depressive disorder (MDD) • Obsessive compulsive disorder (OCD) • Panic disorder (PD) • Social anxiety disorder (SAD) • Generalized anxiety disorder (GAD) • Posttraumatic stress disorder (PTSD) Paroxetine tablets are a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of ( 1 ): • Major Depressive Disorder (MDD) • Obsessive Compulsive Disorder (OCD) • Panic Disorder (PD) • Social Anxiety Disorder (SAD) • Generalized Anxiety Disorder (GAD) • Posttraumatic Stress Disorder (PTSD) […]
On the market
- Earliest approval on file
- December 29, 1992
- Generic labelers
- 45 labelers
- Pharmacy cost
- $0.0611 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 15
Source: FDA drug labels via openFDA (Amitriptyline label of September 8, 2026, Paroxetine label of February 12, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do amitriptyline and paroxetine differ on the record?
In FDA's classes, amitriptyline is a tricyclic antidepressant and paroxetine 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.”; Paroxetine, “The mechanism of action of paroxetine tablets in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central …”
Both labels carry a boxed warning; the records quote them.
Generics: amitriptyline since 1976; paroxetine since 2003 (Drugs@FDA).
| Amitriptyline | Paroxetine | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety, Menopause symptoms |
| 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. | The mechanism of action of paroxetine tablets in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of … |
| Half-life (label) | n/a | Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine tablets. |
| Earliest approval on file (Drugs@FDA) | April 7, 1961 | December 29, 1992 |
| First generic approved | November 16, 1976 | July 30, 2003 |
| 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) | $0.0611 per tablet (Paroxetine HCl 20 mg tablet) |
| 12-month price change | -19% | -16% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 2 | 15 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 17,441 | 41,809 |
| 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.
Paroxetine label, drug interactionsUse caution with concomitant use of BRISDELLE with other drugs that are metabolized by CYP2D6, including nortriptyline, amitriptyline, imipramine, desipramine, fluoxetine, phenothiazines, risperidone, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).
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.
Paroxetine 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