Amitriptyline for Migraine & Headache

Migraine Prophylaxis

Goals of migraine prophylaxis:

  • Reduce the frequency and severity of migraine attacks
  • Improve the patient's quality of life
  • Avoid or minimize overuse of acute headache medication
  • Increase responsiveness of acute attacks to abortive medications


Amitriptyline is a good initial choice for migraine prophylaxis. Although it is not licensed for migraine, amitriptyline is the only antidepressant with the consistent evidence supporting its effectiveness in migraines. Amitriptyline produces a downregulation of serotonin receptors, increases norepinephrine levels at nerve synapses, and enhances endogenous opioid receptor actions.

Amitriptyline may be particularly useful in the patients with mixed migraine and tension-type headaches, and those with comorbid insomnia or depression.

Amitriptyline can significantly reduce the severity, frequency, and duration of migraine attacks 3. Its antimigraine effect is relatively independent of its antidepressant activity 2.

Amitriptyline does not relieve an acute attack of migraine. The acute attack can be aborted with painkillers or triptans.

Amitriptyline dosage for migraine prevention

The dose range for amitriptyline in migraine prevention is 10 to 100 mg per day1. It is recommended to start amitriptyline prophylaxis with a low dose of 10 mg. You can gradually titrate up the dose to achieve the optimal effect (10 mg every week or every two weeks).

It may take 1-3 months for amitriptyline to achieve maximum benefit. Many doctors recommend to stop the prophylaxis treatment after 4-6 months to see if it is still needed.

How effective is Amitriptyline for migraine?

Clinical trial found amitriptyline to be more effective than propranolol in mixed migraine and tension-type headache. However, propranolol works better for migraine alone5.

Amitriptyline works better than dihydroergotamine at reducing headache in patients with mixed migraine and tension-type headaches8.

For patients without insomnia or in those who cannot tolerate amitriptyline, nortriptyline in similar doses may be an alternative. Generally nortriptyline is better tolerated and possibly effective.


Tension-Type Headache

Currently there are no medications approved by the FDA specifically for the treatment of chronic tension-type headache.

Amitriptyline is a best-studied preventive medication for chronic tension-type headache6. This medication is not a painkiller and so does not relieve a headache pain itself. The antidepressant should be taken every day with the aim of preventing headaches.

When taken daily, amitriptyline can reduce headache duration and partly alleviate chronic headaches but cannot entirely eliminate them7.

Amitriptyline is effective for the prophylaxis of frequent headaches in children. A dosing regimen (1 mg/kg per day) can provide an overall perception of being better, and significantly reduce severity and duration of headaches with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day 4.

Amitriptyline dosage for headache

Starting dosage is 10 mg or 25 mg at night. The dosage can be increased by 10 mg or 25 mg every week until a beneficial result is obtained. The average dose of amitriptyline for chronic tension-type headache is 50 to 75 mg per day10.

Once the headaches have been reduced for 4-6 months, the amitriptyline can be stopped. Treatment can be resumed if headaches recur.

Further reading


  • 1. Agency for Healthcare Research and Quality. Canadian Headache Society guideline for migraine prophylaxis.
  • 2. Couch JR, Hassanein RS. Amitriptyline in migraine prophylaxis. Arch Neurol. 1979 Nov;36(11):695-9. PubMed
  • 3. Ziegler DK, Hurwitz A, Preskorn S, Hassanein R, Seim J. Propranolol and amitriptyline in prophylaxis of migraine. JAMA Neurology. 1993 Aug;50(8):825-30.
  • 4. Hershey AD, Powers SW, Bentti AL, Degrauw TJ. Effectiveness of amitriptyline in the prophylactic management of childhood headaches. Headache. 2000 Jul-Aug;40(7):539-49. PubMed
  • 5. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache. 1981
  • 6. Torrente Castells E, Vázquez Delgado E, Gay Escoda C. Use of amitriptyline for the treatment of chronic tension-type headache. Med Oral Patol Oral Cir Bucal. 2008 Sep 1
  • 7. Göbel H, Hamouz V, Hansen C, Heininger K, Hirsch S, Lindner V, Heuss D, Soyka D. Chronic tension-type headache: amitriptyline reduces clinical headache-duration and experimental pain sensitivity but does not alter pericranial muscle activity readings. Pain. 1994 Nov;59(2):241-9.
  • 8. Bonuso S, Di Stasio E, Barone P, Steardo L. Timed - release dihydroergotamin e in the prophylaxis of mixed headache: a study versus amitriptyline. Cephalalgia . 1983;3(suppl 1):175 - 178.
  • 9. Fan W, Lv Y, Ying G, Li W, Zhou J. Pilot study of amitriptyline in the prophylactic treatment of medication-overuse headache. Pain Med. 2014 Oct;15(10):1803-10. PubMed
  • 10. Doyle Strauss L, Weizenbaum E, Loder EW, Rizzoli PB. Amitriptyline Dose and Treatment Outcomes in Specialty Headache Practice: A Retrospective Cohort Study. Headache. 2016 Nov;56(10):1626-1634 PubMed

Published: December 03, 2013
Last reviewed: March 07, 2019

Written by eMedExpert staff

Interesting facts

  • Amitriptyline is useful for medication-overuse headache after abrupt discontinuation of the drug overused9.
  • Interestingly, amitriptyline is the drug of first choice in the US, but not in Europe.

More Facts
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