Amitriptyline for Migraine Prevention

How it works, side effects, and other key facts

Amitriptyline is a tricyclic antidepressant that often is prescribed as a prophylactic medication for migraine headaches. Although it has not been approved by the U.S. Food and Drug Administration (FDA) for preventing migraines, a few studies have shown that it can be effective for this off-label use.

In fact, according to the 2012 guidelines for preventing episodic migraines (defined as headaches that occur fewer than 15 times per month) established by the American Headache Society (AHS) and the American Academy of Neurology (AAN), amitriptyline is a level B medication for migraine prophylaxis, meaning it's regarded as "probably effective."

Man taking medicine
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How It Works

As an antidepressant, amitriptyline increases the levels of neurotransmitters in the brain that affect mood and well-being—specifically, serotonin and norepinephrine. Serotonin is involved in the regulation of blood vessels during a migraine headache, and both chemicals play a role in the processing of pain by the brain.

The effects of amitriptyline on these two brain chemicals are thought to help prevent migraine headaches (as well as chronic tension-type headaches and some other chronic pain conditions). And although research is sparse, studies that have been done to determine how well amitriptyline works as a migraine prophylactic have found it to be effective.


Amitriptyline comes as a tablet you swallow. The smallest dose is 10 milligrams (mg), although the drug is available in larger doses per tablet. The AHS/AAN Guidelines for Prevention of Episodic Migraines recommend between 25 and 150 mg of amitriptyline per day.

It will take some medication adjustment to figure out the best dosage for you. Your healthcare provider likely will start you on a very low dose, wait several weeks for the drug to become established in your system, and then determine if you need to try a higher dose based on how well you tolerate the amitriptyline and whether it seems to be decreasing the number of headaches you have.

Side Effects and Complications

Amitriptyline is associated with a host of side effects—most relatively common and mild, others more serious.

You should see a healthcare provider or go to the nearest hospital emergency department right away if you develop any serious symptoms after taking amitriptyline. Similarly, if you experience mild side effects that become severe or don't go away, let your healthcare provider know.

Mild Side Effects
  • Nausea

  • Vomiting

  • Drowsiness

  • Weakness/fatigue

  • Nightmares

  • Headaches

  • Dry mouth

  • Constipation

  • Difficulty urinating

  • Blurred vision

  • Pain or tingling in hands or feet

  • Changes in sexual function

  • Excessive sweating

  • Changes in appetite

  • Weight loss/weight gain

  • Confusion

  • Balance problems

Serious Side Effects
  • Trouble speaking

  • Dizziness/faintness

  • Weakness/numbness in a limb

  • Crushing chest pain

  • Rapid, pounding, or irregular heartbeat

  • Severe skin rash or hives

  • Swelling of the face and tongue

  • Yellowing of skin or eyes

  • Spasms of the jaw, neck, and/or back muscles

  • Uncontrollable shaking

  • Fainting

  • Unusual bleeding or bruising

  • Seizures

  • Hallucinating

Special Warning

As with many antidepressants, amitriptyline has been found to cause some people who take the drug for depression to develop thoughts of self-harm or become suicidal. Those most likely to be affected in this way are children, teenagers, and young adults under age 24.

A small risk of suicidal thoughts or other changes in mental health also exists for adults over 24, especially at the very beginning of treatment or whenever there is a change in dosage.


There are quite a few medications, both prescription and over-the-counter (OTC), that may interact with amitriptyline. In fact, there are too many to list, so it's very important to be thorough and upfront with your healthcare provider about any medications you take.

Some medications that are known to interact with amitriptyline include:

  • Monoamine oxidase (MAO) inhibitors, such as Marplan (isocarboxazid)
  • Nardil (phenelzine), Eldepryl (selegiline) and Parnate (tranylcypromine)
  • Antihistamines and medications for other cold symptoms or asthma
  • Tagamet (cimetidine)
  • Diet pills
  • Antabuse (disulfiram)
  • Ismelin (guanethidine)
  • Atrovent (ipratropium)
  • Quinidex (quinidine)
  • Tambocor (flecainide) or Rythmol (propafenone)
  • Anti-anxiety drugs, sedatives, sleeping pills, and tranquilizers
  • Medications for irritable bowel disease, mental illness, nausea, Parkinson's disease, ulcers, urinary problems, and thyroid disease
  • Phenobarbitol
  • Other antidepressants, such as fluoxetine (Prozac) and other selective serotonin reuptake inhibitors (SSRIs). Note that if you've stopped taking fluoxetine within the previous five weeks, you should tell your healthcare provider.

Amitriptyline can increase the effects of alcohol. Even if you only have an occasional drink, be aware that you may feel the effects of it more strongly than usual. Drinking substantial amounts of alcohol while taking this drug is not advised.


Amitriptyline isn't safe for everyone, so it's important that the healthcare provider who prescribes it for you knows your complete medical history. People who should not take amitriptyline or who should use it with caution include those with:

  • A history of cardiovascular disease or a recent heart attack
  • Diabetes
  • Liver or kidney impairment
  • Bipolar disorder
  • A seizure disorder
  • Glaucoma, dry eyes, or vision problems
  • Decreased gastrointestinal motility
  • Urinary retention issues
  • An enlarged prostate

Women who are trying to conceive, or are pregnant or breastfeeding should not take amitriptyline. It's not safe for people over 65 and also is likely to be less effective for them than other medications.

A Word From Verywell

Amitriptyline isn't the only antidepressant that's used for migraine prevention, but it's the one that has been studied the most and is prescribed most often. For some people, it can be very effective, but for others, it can cause side effects that make taking it intolerable. Fortunately, it's not the only medication in the migraine prevention arsenal, so if amitriptyline doesn't work for you, there are bound to be other medications and measures you can take to decrease the number of headaches you have.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Loder, E, Burch, R, Rizzoli, P. The 2012 AHS/AAN Guidelines for Prevention of Episodic

    Migraine: A Summary and Comparison With Other Recent

    Clinical Practice Guidelines. Headache 2021. doi:10.1111/j.1526-4610.2012.02185.x

  2. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adultsCochrane Database Syst Rev. 2015;2015(7):CD008242. doi:10.1002/14651858.CD008242.pub3

  3. Thour A, Marwaha R. Amitriptyline. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

  4. Burch R. Antidepressants for Preventive Treatment of MigraineCurrent Treatment Options in Neurology. 2019;21(4). doi:10.1007/s11940-019-0557-2

Additional Reading

By Teri Robert
 Teri Robert is a writer, patient educator, and patient advocate focused on migraine and headaches.