Medication profile
Amitriptyline (Adepril)
Amitriptyline is a tricyclic antidepressant (TCA) used primarily for depression and, at lower doses, for several types of chronic pain and other conditions.
Written by Sanjida Ahmed, PhD, Cellular and Molecular BiologyChief Operating Officer and Lead Scientist, Personalized Prescribing. Last reviewed October 2, 2026.
- Brand Names
- Adepril, Amitid, Amitril, Amitryp, Elavil, Elatrol, Endep, Fiorda, Kamitrin, Laroxyl, Latilin, Maxitrip, Redomex, Saroten, Sarotex, Syneudon, Tryptanol and Tryptizol.
- Other historical or international names
- Other historical or international names include: Adepress, Conmitrip, Damilan, Damilen, Elanil, Flavyl, Lantron, Lentizol, Seroten, Sylvemid, Triptanol, Triptisol and Uxen Retard.
- Class
- Tricyclic antidepressant
On this page
What you need to know
Amitriptyline is a tricyclic antidepressant (TCA) used primarily for depression and, at lower doses, for several types of chronic pain and other conditions.
What is Amitriptyline used for?
Amitriptyline may be prescribed for:
- Major depressive disorder
- Neuropathic pain
- Chronic pain syndromes
- Migraine prevention
- Certain sleep-related symptoms associated with pain The dose and treatment strategy can differ considerably depending on the condition being treated.
What are the common side effects of Amitriptyline?
Common adverse effects can include:
- Dry mouth
- Constipation
- Drowsiness
- Dizziness
- Blurred vision
- Increased appetite
- Weight gain
- Difficulty urinating Some adverse effects may be more likely when drug exposure is elevated.
Important
Amitriptyline can also have clinically significant effects involving cardiac conduction, blood pressure and the central nervous system. Serious or unusual symptoms should be discussed promptly with a healthcare professional.
Drug Interactions
Amitriptyline can interact with other medications. (Drug Interactions)
Particularly important considerations include medications:
MAO inhibitors — Avoid/Contraindicated
Examples:
- Phenelzine
- Tranylcypromine
- Isocarboxazid
- Selegiline Combination can produce severe, potentially life-threatening reactions. Appropriate washout periods are important when switching between an MAOI and amitriptyline.
Fluoxetine — Inhibitor of liver enzyme CYP2D6
Fluoxetine strongly inhibits the liver enzyme CYP2D6, which can reduce the metabolism of amitriptyline and increase its concentration in the body. Higher amitriptyline exposure may increase the risk of concentration-related adverse effects and toxicity.
There is also an additive serotonergic effect, increasing the risk of serotonin syndrome.
Importantly, fluoxetine has a long half-life, so the prescribing information recommends allowing at least 5 weeks after stopping fluoxetine before initiating a TCA in relevant circumstances.
Paroxetine — Inhibitor of liver enzyme CYP2D6
Paroxetine strongly inhibits the liver enzyme CYP2D6, which can reduce the metabolism of amitriptyline and increase its concentration in the body. Higher amitriptyline exposure may increase the risk of concentration-related adverse effects and toxicity.
It can also increase serotonergic activity. Monitoring for TCA toxicity and, where appropriate, plasma TCA concentrations are recommended when these drugs are combined.
Bupropion — Inhibitor of liver enzyme CYP2D6
Bupropion strongly inhibits the liver enzyme CYP2D6, which can reduce the metabolism of amitriptyline and increase its concentration in the body. Higher amitriptyline exposure may increase the risk of concentration-related adverse effects and toxicity.
A patient who is genetically a CYP2D6 normal metabolizer can have their functional CYP2D6 activity substantially reduced by a strong inhibitor.
The amitriptyline label explicitly notes that CYP2D6-inhibiting drugs can make a normal metabolizer functionally resemble a poor metabolizer.
Cimetidine
Cimetidine strongly inhibits the liver enzyme CYP2D6, which can reduce the metabolism of amitriptyline and increase its concentration in the body. Higher amitriptyline exposure may increase the risk of concentration-related adverse effects and toxicity.
Reported consequences include greater anticholinergic effects, drowsiness, cardiovascular effects and other manifestations of TCA toxicity.
Dosage Amitriptyline is generally started low and taken in the evening, because sedation is common.
A Canadian neuropathic-pain guideline similarly describes starting at 10–25 mg/day and increasing by about 10 mg weekly, with maintenance commonly in the 10–100 mg/day range. The actual schedule should be individualized rather than treated as a fixed protocol.
The dosing can be substantially higher when amitriptyline is being used as an antidepressant.
The US prescribing information recommends starting at a low dose and increasing gradually according to response and tolerability. For adults treated as outpatients, it describes 75 mg/day in divided doses as a usual starting regimen, with increases up to 150 mg/day when necessary. It also describes an alternative bedtime initiation of 50–100 mg, increased by 25–50 mg as necessary.
However, in contemporary clinical practice, clinicians may use lower starting doses and slower titration, particularly in older adults or patients who are sensitive to sedation, anticholinergic effects or cardiovascular effects.
The maintenance dose in the product information is generally 50–100 mg/day, with the dose reduced to the lowest amount that maintains clinical benefit. Daily Med
Amitriptyline should generally not be stopped abruptly after regular use.
Abrupt discontinuation can produce withdrawal/discontinuation symptoms such as:
- nausea
- dizziness
- headache
- sleep disturbance
- anxiety/agitation
- sweating
- flu-like symptoms
- gastrointestinal symptoms
- sensory symptoms NICE recommends tapering antidepressants when withdrawing treatment, with the taper adjusted according to the dose and the person’s discontinuation symptoms.
There isn’t one universally applicable amitriptyline taper.
A practical example might be:
75 mg → 50 mg → 25 mg → 10 mg → stop
with each reduction separated by 1–2 weeks or longer, depending on duration of treatment, dose, indication and symptoms.
For someone who has taken amitriptyline for a long time or who develops significant withdrawal symptoms, a much slower taper may be appropriate. One NHS neuropathic pain guideline recommends withdrawal over at least 4 weeks when amitriptyline is not tolerated, while emphasizing that the exact regimen needs to be individualized.
Frequently Asked Questions
Is Amitriptyline an antidepressant?
Yes. It is a tricyclic antidepressant, although it is also commonly prescribed at lower doses for conditions such as neuropathic pain and migraine prevention.
Does Amitriptyline make you sleepy?
It can. Amitriptyline has significant antihistamine activity, which can contribute to sedation.
What does amitriptyline do to serotonin?
Amitriptyline inhibits the reuptake of serotonin, allowing more serotonin to remain available between nerve cells and altering serotonin signaling throughout the brain.
What does amitriptyline do to norepinephrine?
Amitriptyline also inhibits norepinephrine reuptake. Increased norepinephrine signaling can affect mood, energy, attention and the descending pathways that help control pain.
Is amitriptyline used for nerve pain?
Yes. Amitriptyline is commonly used for certain forms of neuropathic or chronic pain because serotonin and norepinephrine help regulate how pain signals are processed in the brain and spinal cord.
Why is amitriptyline taken at night?
Amitriptyline can cause significant drowsiness because it affects histamine and other receptors involved in wakefulness. For this reason, it is frequently taken in the evening, particularly when prescribed for pain.
How long does amitriptyline take to work?
Its sedating effects may occur relatively quickly, while improvements in pain or depression usually take longer. The timing varies depending on the condition being treated, dose and individual response.
Can genetics affect amitriptyline side effects?
Yes. Genetic differences in CYP2D6 and CYP2C19 can influence the concentration of amitriptyline and its metabolites in the body, which may contribute to differences in effectiveness or side effects.
Can amitriptyline fail even if CYP2D6 and CYP2C19 are normal?
Yes. Drug metabolism is only one part of medication response. The medication must also interact effectively with its targets and produce beneficial changes within the relevant brain and nervous-system pathways.
Should I change my Amitriptyline dose based on my genetic result?
No. Genetic results should be interpreted by a qualified healthcare professional in the context of your diagnosis, other medications, medical history and treatment response.
Can pharmacogenomic testing tell me whether Amitriptyline will work?
PGx testing does not guarantee whether a medication will work. It provides genetic information that may help predict drug metabolism and, for some medications, treatment response or adverse-effect risk.
Why Pharmacogenomic Testing May Matter?
Two patients taking the same dose of amitriptyline can have very different drug exposure.
One patient may experience:
Too much drug → adverse effects
while another may experience:
Too little drug → inadequate response
Pharmacogenomic testing can help identify genetic factors that may contribute to these differences.
References
This article is educational. It does not diagnose, and it does not replace advice from your prescriber or pharmacist. Never start, stop or change a medication based on a web page.