Two medicines, side by side
Amitriptyline vs venlafaxine
Amitriptyline and venlafaxine are both labeled for depression. Drugs@FDA records approvals of amitriptyline since 1961 and of venlafaxine since 1993. Pharmacies paid $0.03 per amitriptyline HCl 10 mg tablet and $0.0799 per venlafaxine HCl ER 75 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 venlafaxine a serotonin and norepinephrine reuptake inhibitor.
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026); the venlafaxine FDA label on DailyMed (effective August 15, 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 venlafaxine record
Venlafaxine (Effexor) · label of August 15, 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 emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ]. Effexor XR is not approved for use in pediatric patients [see Use in Specific Populations (8.4) ].
Used for
From the label: indicationsEffexor XR is indicated in adults for the treatment of: • Major Depressive Disorder (MDD) [see Clinical Studies (14.1) ] • Generalized Anxiety Disorder (GAD) [see Clinical Studies (14.2) ] • Social Anxiety Disorder (SAD) [see Clinical Studies (14.3) ] • Panic Disorder (PD) [see Clinical Studies (14.4) ] Effexor XR is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with: • Major Depressive Disorder (MDD) ( 1 ) • Generalized Anxiety Disorder (GAD) ( 1 ) • Social Anxiety Disorder (SAD) ( 1 ) • Panic Disorder (PD) […]
On the market
- Earliest approval on file
- December 28, 1993
- Generic labelers
- 61 labelers
- Pharmacy cost
- $0.0799 per capsule
Supply and safety
- Shortage
- No current entry
- Recalls
- 21
Source: FDA drug labels via openFDA (Amitriptyline label of September 8, 2026, Venlafaxine label of August 15, 2023); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do amitriptyline and venlafaxine differ on the record?
In FDA's classes, amitriptyline is a tricyclic antidepressant and venlafaxine 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.”; Venlafaxine, “The mechanism of action of venlafaxine in the treatment of MDD, GAD, SAD, and PD is unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous …”
Both labels carry a boxed warning; the records quote them.
Generics: amitriptyline since 1976; venlafaxine since 2006 (Drugs@FDA).
| Amitriptyline | Venlafaxine | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety |
| 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. | The mechanism of action of venlafaxine in the treatment of MDD, GAD, SAD, and PD is unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their … |
| Half-life (label) | n/a | The apparent elimination half-life is 5 ± 2 hours for venlafaxine and 11 ± 2 hours for ODV. |
| Earliest approval on file (Drugs@FDA) | April 7, 1961 | December 28, 1993 |
| First generic approved | November 16, 1976 | August 3, 2006 |
| Generic labelers (NDC) | 34 labelers | 61 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.03 per tablet (Amitriptyline HCl 10 mg tablet) | $0.0799 per capsule (Venlafaxine HCl ER 75 mg capsule) |
| 12-month price change | -19% | -13% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 2 | 21 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 17,441 | 131,560 |
| 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.
Venlafaxine label, drug interactionsOther Serotonergic Drugs Clinical Impact Concomitant use of Effexor XR with other serotonergic drugs (including other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome.
Source: FDA drug labels via openFDA
What next?
- Alternatives to amitriptyline
- every medicine labeled for the same conditions