Amitriptyline
Amitriptyline is one of the oldest tricyclic antidepressants, in clinical use since 1961. Today it is more commonly used at low dose for neuropathic pain, chronic pain syndromes, migraine prevention and insomnia than for depression, where SSRIs and SNRIs have largely replaced it.
- Chemical formula
- C20H23N
- CAS number
- 50-48-6
- ATC code
- N06AA09
- Molecular weight
- 277.40 g/mol
- Drug class
- Tricyclic antidepressant (TCA)
- Also known as
- Elavil, Endep, Tryptizol, Saroten
What is it?
Amitriptyline is a tricyclic antidepressant (TCA) introduced in 1961, one of the most widely used members of the class. It was a mainstay antidepressant before the SSRIs arrived in the late 1980s and remains on the WHO Essential Medicines List. Marketed as Elavil (US, historically), Endep (Australia), Tryptizol and Saroten (Europe). Authorised generic amitriptyline has been available for decades and is now the standard form. Modern use is dominated by off-label low-dose indications: chronic pain, migraine prevention and insomnia, with major depression a less common indication.
Mechanism of action
Amitriptyline inhibits the reuptake of serotonin and noradrenaline at central synapses, raising synaptic levels of both neurotransmitters. It also has substantial antagonism at H1 histamine, muscarinic acetylcholine, α1-adrenergic and 5-HT2 receptors, which explains both adverse effects (sedation, dry mouth, orthostatic hypotension) and useful low-dose actions (sleep induction, neuropathic pain modulation through descending inhibitory pathways).
Pharmacokinetics
Amitriptyline is well absorbed orally with peak plasma at 4–8 hours. Hepatic CYP2D6 demethylation produces nortriptyline, an active metabolite that is itself a marketed TCA. The terminal half-life of amitriptyline is 10–28 hours, supporting once-daily bedtime dosing. CYP2D6 polymorphism produces meaningful interindividual variability; poor metabolisers reach higher levels at standard doses.
Indications
Amitriptyline is approved for major depressive disorder, but contemporary use is dominated by low-dose off-label indications: neuropathic pain, fibromyalgia, chronic tension headache, migraine prevention, irritable bowel syndrome, nocturnal enuresis, and insomnia. According to current pain guidelines, amitriptyline 10–25mg at bedtime is first-line for many neuropathic pain conditions despite limited specific approval. For depression, doses are higher (75–150mg) and SSRIs are typically preferred first-line.
Safety profile
Common adverse effects reflect anticholinergic, antihistaminic and α1-blocking activity: dry mouth, constipation, urinary hesitancy, blurred vision, sedation, weight gain and orthostatic hypotension. Cardiac conduction effects (QT prolongation, arrhythmia) make amitriptyline particularly dangerous in overdose, with mortality at high ingested doses. Older adults are sensitive to anticholinergic effects and falls. According to current geriatric guidelines, amitriptyline is on the Beers criteria list of medications to avoid in older adults where possible.
Products containing this ingredient
Frequently asked questions
Why is amitriptyline used for pain instead of depression today? ▾
At low doses (10–25mg at bedtime), amitriptyline modulates descending inhibitory pain pathways through its noradrenaline reuptake inhibition without producing full antidepressant effect. Decades of use and randomised trials support its efficacy in neuropathic pain, fibromyalgia and migraine prevention. According to current guidelines, low-dose amitriptyline is first-line in many chronic pain conditions despite the depression-era branding.
Is amitriptyline still safe given the SSRI alternatives? ▾
Amitriptyline at antidepressant doses (75–150mg) carries higher cardiac and anticholinergic risks than SSRIs and is dangerous in overdose. Low-dose use (10–50mg) for pain or sleep is generally well tolerated in younger patients. According to current geriatric guidelines, it is on the Beers list to avoid in older adults where possible because of fall and cognitive risks.
Why is amitriptyline taken at bedtime? ▾
The strong antihistamine effect produces marked sedation, which makes morning use impractical for most patients but a useful effect at bedtime — particularly for patients with chronic pain plus insomnia. According to clinical practice, 25mg at bedtime often improves sleep within nights while pain modulation builds over weeks. Daytime sedation is the most common cause of dose limitation.
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