Two medicines, side by side

Imipramine vs amitriptyline

Imipramine and amitriptyline are both labeled for depression. Drugs@FDA records approvals of imipramine since 1959 and of amitriptyline since 1961. Pharmacies paid $0.0698 per imipramine HCl 10 mg tablet and $0.03 per amitriptyline HCl 10 mg tablet (NADAC, October 7, 2026). How each works, in its label's words: Imipramine, “of imipramine hydrochloride, is not definitely known.”; Amitriptyline, “It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.”

Check it at the source: the imipramine FDA label on DailyMed (effective August 11, 2026); the amitriptyline FDA label on DailyMed (effective September 8, 2026).

Highlights of the imipramine record

Imipramine (Presamine) · label of August 11, 2026

Boxed warning

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 imipramine 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: indications
Depression - For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. One to three weeks of treatment may be needed before optimal therapeutic effects are evident. […]

On the market

Earliest approval on file: April 16, 1959
Generic labelers: 14 labelers
Pharmacy cost: $0.0698 per tablet

Supply and safety

Shortage: No current entry
Recalls: 4

Highlights of the amitriptyline record

Amitriptyline (Elavil) · label of September 8, 2026

Boxed warning

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: indications
For 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

Source: FDA drug labels via openFDA (Imipramine label of August 11, 2026, Amitriptyline label of September 8, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)

How do imipramine and amitriptyline differ on the record?

How each works, in its label's words: Imipramine, “of imipramine hydrochloride, is not definitely known.”; Amitriptyline, “It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.”

Both are in FDA's class tricyclic antidepressants.

Both labels carry a boxed warning; the records quote them.

Generics: imipramine since 1974; amitriptyline since 1976 (Drugs@FDA).

	Imipramine	Amitriptyline
Labeled for	Depression	Depression
Pharmacologic class	Tricyclic Antidepressant	Tricyclic Antidepressant
How it works (label)	of imipramine hydrochloride, is not definitely known. However, it does not act primarily by stimulation of the central nervous system.	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.
Half-life (label)	n/a	n/a
Earliest approval on file (Drugs@FDA)	April 16, 1959	April 7, 1961
First generic approved	June 27, 1974	November 16, 1976
Generic labelers (NDC)	14 labelers	34 labelers
Pharmacy cost (NADAC, each one's most listed form; strengths differ)	$0.0698 per tablet (Imipramine HCl 10 mg tablet)	$0.03 per tablet (Amitriptyline HCl 10 mg tablet)
12-month price change	-12%	-19%
Boxed warning	Yes	Yes
Shortage now	No current entry	No current entry
Recalls recorded	4	2
FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used)	723	17,441
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, warnings
If 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.

Source: FDA drug labels via openFDA

What next?

Imipramine: the full record
Amitriptyline: the full record
Alternatives to imipramine: every medicine labeled for the same conditions