[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) › Amitriptyline

[Pharmacology](https://durgical.com/en/pharmacology/) · [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/)

# Amitriptyline

A classic tricyclic antidepressant on the WHO list, now often used for nerve pain and migraine prevention. Sedating, anticholinergic, dangerous in overdose.

Updated 2026-11-01

- Class: [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/)
- Transporter: Norepinephrine transporter (NET) and serotonin transporter (SERT)
- ATC code: N06AA09
- WHO Model List of Essential Medicines

⇄**Norepinephrine transporter (NET) and serotonin transporter (SERT)**Amitriptyline

ⓘ The figure shows amitriptyline bound to human NET in an outward-open state.

**Target in 3D:** Norepinephrine transporter (NET) and serotonin transporter (SERT). PDB structure 8Y93 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8Y93) · Drag to rotate · pinch to zoom

## Mechanism of action

Amitriptyline blocks the membrane pumps that take norepinephrine and serotonin back into neurons. It also blocks muscarinic, histamine H1 and alpha-1 adrenergic receptors, which explains much of its adverse-effect profile, and at high levels it blocks cardiac fast sodium channels.

- Amitriptyline blocks NET and SERT
- Norepinephrine and serotonin act longer in the synapse
- It also blocks muscarinic, H1 and alpha-1 receptors
- In overdose it blocks cardiac sodium channels and widens the QRS

## Pharmacokinetics

**Absorption**
Rapidly absorbed by mouth

**Metabolism**
In the liver by N-demethylation and hydroxylation; CYP2D6 poor metabolisers and CYP2D6 inhibitors raise tricyclic levels

**Elimination**
Almost entirely as metabolites in the urine

**Onset and duration**
Sedation appears early; the antidepressant effect takes weeks

## Indications

- Depression
- Post-herpetic neuralgia (pain after shingles) [Herpes zoster (shingles) →](https://durgical.com/en/conditions/herpes-zoster/)
- Migraine prevention [Migraine →](https://durgical.com/en/conditions/migraine/)
- Symptom control in palliative care (WHO list)

## Adverse effects

### Common

- Dry mouth, constipation, blurred vision, urinary retention (anticholinergic)
- Sedation and weight gain (H1 block)
- Orthostatic hypotension and dizziness (alpha-1 block)
- Tachycardia and ECG changes
- Confusion, especially in older adults

### Serious (rare, important)

- Fatal toxicity in overdose: arrhythmias, QRS widening, hypotension, seizures, coma
- Suicidal thoughts and behaviour in young people (boxed warning)
- Serotonin syndrome
- Paralytic ileus and urinary retention
- Angle-closure glaucoma
- Hyponatraemia (SIADH)
- Bone marrow depression (rare)

## Contraindications

- MAO inhibitors, or within 14 days of stopping one (hyperpyrexia, convulsions, deaths)
- Acute recovery phase after myocardial infarction
- Cisapride (QT prolongation)
- Hypersensitivity to amitriptyline

## Key interactions

**MAO inhibitors, linezolid, intravenous methylene blue**
Serotonin syndrome and hyperpyretic crises

**CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine), cimetidine**
Higher tricyclic levels and toxicity

**Other anticholinergic drugs**
Paralytic ileus, urinary retention, hyperthermia

**Alcohol and other CNS depressants**
Additive sedation and respiratory depression

**Sympathomimetics, including epinephrine in local anaesthetics**
Exaggerated pressor and cardiac effects; close supervision needed

## What is monitored

- ECG in older adults or heart disease
- Orthostatic blood pressure and falls
- Anticholinergic effects: bowel habit, urination, confusion
- Mood and suicidal thoughts; plasma levels when combined with CYP2D6 inhibitors

## Administration and safety

- Given by mouth; because of its sedation, the label prefers a bedtime dose for maintenance
- People at risk of suicide get the smallest practical supply, because a large overdose can be fatal
- Stopped gradually; abrupt cessation can cause nausea, headache and malaise
- Stopped several days before elective surgery when possible (label)

## Nursing care

- Check orthostatic blood pressure and fall risk, especially in older adults
- Ask about constipation, urinary retention and blurred vision; teach fluids, fibre and when to report
- Assess suicide risk and limit the amount of medicine available at home
- Know the overdose signs: drowsiness, confusion, dilated pupils, tachycardia, seizures and a wide QRS on the ECG
- Warn about alcohol and driving while drowsy

## Pregnancy and breastfeeding

Crosses the placenta; there are a few reports of problems in exposed infants without proven cause, so it is used only when the benefit justifies the possible risk.

## Memory aid

Tricyclic «tri» trouble in overdose: Convulsions, Coma, Cardiotoxicity; the wide QRS calls for bicarbonate.

## Test yourself

Think of the answer, then tap the question to see it.

## What ECG finding is the best marker of severity in tricyclic overdose, and what treats it?

Widening of the QRS complex (sodium-channel block). Intravenous sodium bicarbonate is given to alkalinise and load sodium, which narrows the QRS.

## Which receptor blocks explain amitriptyline's dry mouth, sedation and orthostatic hypotension?

Muscarinic block (dry mouth, constipation, urinary retention), H1 block (sedation, weight gain) and alpha-1 block (orthostatic hypotension).

## Which two non-depression uses of amitriptyline are most common?

Post-herpetic neuralgia and migraine prevention; it is also on the WHO list for symptom control in palliative care.

## Why is amitriptyline avoided right after a myocardial infarction?

It can cause arrhythmias, conduction changes and tachycardia; the label excludes the acute recovery phase after infarction.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/amitriptyline/)

## Related drugs

- [Duloxetine](https://durgical.com/en/pharmacology/duloxetine/)
- [Phenelzine](https://durgical.com/en/pharmacology/phenelzine/)

## Related conditions

- [Herpes zoster (shingles)](https://durgical.com/en/conditions/herpes-zoster/)
- [Migraine](https://durgical.com/en/conditions/migraine/)

[← Back to the class: Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - AMITRIPTYLINE HYDROCHLORIDE tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e520c63-1cf6-40f6-a51c-3f9b0e181342) (DailyMed (U.S. National Library of Medicine), 2026); [Amitriptyline: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682388.html) (MedlinePlus (U.S. National Library of Medicine), 2024); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=amitriptyline) (World Health Organization, 2025); [8Y93: Structure of NET-Amitriptyline in outward-open state](https://www.rcsb.org/structure/8Y93) (RCSB Protein Data Bank, 2024).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/amitriptyline/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/amitriptyline/