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Amitriptyline: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Nov 6, 2019.

1. How it works

  • Amitriptyline is used to treat depression and is thought to work by increasing levels of serotonin and/or norepinephrine in the brain.
  • Amitriptyline belongs to a group of medicines known as tricyclic antidepressants.

2. Upsides

  • May be used for the treatment of major depressive disorder (MDD).
  • May be used off-label (this means it is not an FDA-approved indication; however it may be useful clinically) for the treatment of other conditions such as chronic pain, fibromyalgia, or insomnia. Amitriptyline may be used in addition to other treatments or where alternative treatments have not worked.
  • Recommended on the WHO pain ladder for nerve-related pain unresponsive to opioid-like drugs (such as morphine).
  • Generic amitriptyline is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Dry mouth, headache, constipation, diarrhea, and sexual dysfunction.
  • May increase the risk of suicidal thoughts or behavior in young adults (similar to other antidepressants).
  • May cause drowsiness and affect a person's ability to drive or operate machinery; some people may develop tolerance to this effect.
  • Risk of heart-related effects, muscle rigidity, tremor, seizures, increased sensitivity to light, weight gain or loss, hair loss, skin rash, and edema.
  • Interaction or overdosage may cause serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremor, nausea, vomiting, diarrhea).
  • May cause withdrawal symptoms with abrupt discontinuation (symptoms include nausea, headache, sleep disturbance, and generalized tiredness). These are not indicative of addiction. Taper dosage off slowly under medical supervision.
  • May interact with a number of other drugs including those that are metabolized by hepatic enzymes CYP2D6 or other drugs that cause sedation or with anticholinergic side effects (such as dry mouth, urinary retention, blurred vision, constipation). Extremely high fever (hyperpyrexia) has been reported when amitriptyline has been administered with antipsychotics or anticholinergic drugs.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Amitriptyline is an effective antidepressant but may cause drowsiness initially and a withdrawal syndrome with abrupt discontinuation.

5. Tips

  • Take higher dosages late in the afternoon or in the evening to minimize daytime sedation.
  • Do not stop suddenly as withdrawal symptoms may occur. Reducing the dosage slowly over weeks to months is recommended.
  • Tell your doctor if your depression worsens or if you develop suicidal thoughts, particularly during the first few months of therapy. Also, monitor for serotonin syndrome.
  • Report any unusual side effects to a doctor.
  • May increase the risk of sunburn; protect yourself from the sun when outdoors.
  • Do not take other medications with amitriptyline until first checking with your doctor or pharmacist that these are compatible.

6. Response and Effectiveness

  • Peak concentrations of amitriptyline are reached within 4 to 8 hours. Amitriptyline is metabolized to an active metabolite (nortriptyline) so the effects of amitriptyline are long-lasting. The antidepressant effect may take several weeks to develop.

7. Interactions

Medicines that interact with amitriptyline may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with amitriptyline. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with amitriptyline include:

  • anticoagulants (blood thinners), such as warfarin, or other drugs that have blood-thinning effects such as aspirin or NSAIDs
  • anticonvulsants, such as phenytoin, phenobarbital, or primidone
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
  • aspirin
  • bupropion
  • buspirone
  • cimetidine
  • diuretics, such as furosemide
  • disulfiram
  • ipratropium
  • lithium
  • medications that may affect the heartbeat by prolonging the QT interval, such as amiodarone, encainide, flecainide, or pimozide
  • medications that induce or inhibit CYP2D6 such as amiodarone, bupropion, or duloxetine
  • other antidepressants, such as tricyclic antidepressants (eg, clomipramine), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), venlafaxine, and SSRIs (eg, paroxetine, sertraline)
  • other medications that affect serotonin, such as amphetamines, fentanyl, lithium, tramadol, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort
  • others, such as HIV medications (fosamprenavir, ritonavir), fluconazole, or procyclidine.

Avoid drinking alcohol or taking illegal or recreational drugs while taking amitriptyline.

Note that this list is not all-inclusive and includes only common medications that may interact with amitriptyline. You should refer to the prescribing information for amitriptyline for a complete list of interactions.


Amitriptyline. Revised 08/2019.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use amitriptyline only for the indication prescribed.

Copyright 1996-2021 Revision date: November 6, 2019.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.