amitriptyline
Meaning of amitriptyline: Better known today for nerve pain, migraine and sleep than for depression, this older antidepressant acts on a wide range of receptors.
Definition of amitriptyline
Amitriptyline is a tricyclic antidepressant, named for the three fused rings in its chemical structure, that raises the amount of serotonin and norepinephrine available between nerve cells. It was introduced as a treatment for depression, and low doses are now widely prescribed for nerve pain, migraine prevention and difficulty sleeping.
What is it used for?
| Use | How it is usually given |
|---|---|
| Depression | Higher doses, with the effect on mood building over weeks |
| Nerve pain | Low doses; the pain effect does not depend on treating depression |
| Migraine prevention | Low doses taken regularly rather than during an attack |
| Difficulty sleeping | Low doses, making use of the sedating effect |
| Other | Anxiety and irritable bowel symptoms in some settings |
Prescribing for pain and sleep frequently falls outside the approved label in a given country, which is lawful and routine where evidence supports it. Being given amitriptyline therefore says nothing by itself about whether a person is being treated for depression.
Why does one drug have so many effects?
It blocks the transporters that draw serotonin and norepinephrine back into the nerve cell after release, leaving more of each in the gap between cells. That much it shares with newer antidepressants. What sets it apart is everything else it blocks. Histamine receptors, producing drowsiness and increased appetite. Muscarinic acetylcholine receptors, producing dry mouth, blurred vision, constipation and difficulty passing urine. Alpha-1 adrenergic receptors, allowing blood pressure to fall on standing. Blockade of sodium channels contributes to the effect on nerve pain and also to the danger in overdose. Older adults are more sensitive to the anticholinergic and blood pressure effects than younger adults. The sedating effect appears from the first dose while the effect on mood takes weeks, so the two are easily mistaken for each other.
How does it compare with newer antidepressants?
| Tricyclics such as amitriptyline | SSRIs | |
|---|---|---|
| Main targets | Serotonin and norepinephrine, plus histamine, acetylcholine and alpha receptors | The serotonin transporter, largely on its own |
| Usual effects | Drowsiness, dry mouth, constipation, dizziness on standing | Nausea, changed sleep, sexual effects |
| Overdose | Narrow margin, with heart rhythm disturbance the main danger | Wider margin |
| Use in pain | Established at low dose | Limited |
A separate and still investigational use, studied rather than established, is amitriptyline taken by mouth or applied to the skin for the nerve pain that follows certain chemotherapy drugs.
Also known as
Used in a sentence
Amitriptyline was prescribed at a low dose for the patient's chronic pain rather than for depression.
Good to know
Amitriptyline belongs to the older tricyclic class, which acts on several receptor systems beyond serotonin, and that breadth accounts both for its use in pain and sleep and for a narrower margin between a useful and a toxic amount than newer antidepressants carry.