Amitriptyline
ElavilPubChem CID 2160 · 3D model
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Raises both serotonin and norepinephrine like the newer SNRIs venlafaxine and duloxetine, but through an older, less selective tricyclic structure that also blocks several other brain signals — causing dry mouth, drowsiness, and dizziness on standing — which is why cleaner-acting antidepressants have largely replaced it despite similar effectiveness.
How it works
Amitriptyline works partly like the newer antidepressants on this site: it raises levels of serotonin and norepinephrine by blocking their reabsorption into nerve cells, the same two targets venlafaxine and duloxetine hit with newer, more selective molecules. But amitriptyline's older, boxier chemical structure also blocks several other signals those newer drugs mostly leave alone — one involved in digestion and saliva (causing dry mouth and constipation), one involved in alertness (causing drowsiness), and one involved in blood vessel tone (causing dizziness on standing). This broad, less-selective profile is a big part of why TCAs like amitriptyline, though effective, were largely replaced by cleaner-acting antidepressants. It's chemically a close cousin of cyclobenzaprine, also on this site, a muscle relaxant that shares much of this same tricyclic chemistry and side-effect profile.
What it’s used for
Officially, amitriptyline's FDA approval covers one thing: depression. In practice, doctors also prescribe it very often off-label — meaning outside that official approval, based on other evidence — for nerve pain and to help prevent migraines. Those uses are common and well-supported by clinical experience, but they were never the basis of its FDA approval the way depression was.
- Mechanism
- Tricyclic antidepressant (TCA) — nonselective serotonin/norepinephrine reuptake inhibitor with muscarinic, H1, and alpha-1 adrenergic antagonism
- Drug class
- Small molecule
- Therapeutic area
- CNS / Psychiatric