Amitriptyline: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Oct 3, 2023.

1. How it works

• Amitriptyline may be used to treat depression or off-label to relieve chronic pain, fibromyalgia, or insomnia.
• Experts are unsure exactly how amitriptyline works, although historically it was believed that amitriptyline’s effects for depression were due to its ability to rebalance chemicals in the brain, such as serotonin and/or norepinephrine. Studies confirm that amitriptyline is still effective for treating mood disorders, such as depression, even though the way it works is unknown. It is not known how amitriptyline works to relieve chronic pain, fibromyalgia, or insomnia.
• 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.
• There is a risk of heart-related side effects with amitriptyline, as well as muscle rigidity, tremors, 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 tremors, nausea, vomiting, or diarrhea). Another rare syndrome, neuroleptic malignant syndrome (NMS) has been reported after starting or increasing the dose of amitriptyline. Symptoms include muscle rigidity, fever, mental status changes, a fast heart rate, and tremors.
• 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. Rare instances of mania have been reported within 2 to 7 days following cessation of chronic treatment with tricyclic antidepressants, such as amitriptyline.
• May not be suitable for some people including those who are in the acute recovery phase following a myocardial infarction, undiagnosed bipolar disorder, a history of seizures, urinary retention, or angle-closure glaucoma. Do not use high dosages of amitriptyline in people with cardiovascular disease. Close supervision is recommended when giving to people with thyroid disease.
• May cause mild pupil dilation, which may trigger an episode of angle-closure glaucoma.
• May interact with several 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.
• Not approved for use in children.
• Do not use during pregnancy unless the benefits outweigh the risks. Amitriptyline has been shown to cross the placenta and there have been a few reports of adverse events, although a causal relationship has not been established.

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 it may cause drowsiness initially and a withdrawal syndrome with abrupt discontinuation. It may be used off-label to treat other conditions such as chronic pain, fibromyalgia, or insomnia.

5. Tips

• Take exactly as your doctor has prescribed. If amitriptyline makes you sleepy, talk to your doctor about taking higher dosages later in the afternoon or in the evening to minimize daytime sedation.
• Read the medication guide supplied by your pharmacy that tells you about amitriptyline. If you have any further questions, talk with your doctor or pharmacist.
• 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.
• Tell your doctor if you are pregnant or intending to become pregnant, or breastfeeding.

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, 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
• cisapride
• 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
• topiramate.

May enhance the effects of alcohol and the effects of other CNS depressants. 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.

References

• Amitriptyline. Revised 09/2023. ASHP monographs. https://www.drugs.com/monograph/amitriptyline.html

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.

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

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