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Updated: Sep 4, 2025

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Amitriptyline for post-COVID headache: effectiveness, tolerability, and response predictors.

Alicia Gonzalez-Martinez1,2,3, Ángel Luis Guerrero-Peral4,5, Susana Arias-Rivas6

  • 1Headache Unit, Department of Neurology, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS Princesa), Madrid, Spain.

Journal of Neurology
|July 13, 2022
PubMed
Summary

Amitriptyline (AMT) effectively reduced headache days in post-COVID-19 patients, particularly those with a history of tension-type headache (TTH). This treatment showed good tolerability and potential benefits for managing persistent headaches after infection.

Keywords:
Adverse eventsAmitriptylineCOVID-19Long-haulersLong-term effectMigrainePost-COVID-19 headacheReal-world effectivenessReal-world evidenceTension-type headache

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Area of Science:

  • Neurology
  • Infectious Diseases
  • Pharmacology

Background:

  • Post-COVID-19 headache is a common and debilitating symptom.
  • The headache often presents with features of both tension-type headache (TTH) and migraine.
  • Understanding effective treatments for post-COVID-19 headache is crucial.

Purpose of the Study:

  • To evaluate the real-world effectiveness of amitriptyline (AMT) for post-COVID-19 headache.
  • To assess the side effects associated with AMT treatment.
  • To identify predictors of response to AMT in this patient population.

Main Methods:

  • An observational, multicentric, retrospective cohort study was conducted.
  • Patients receiving AMT for post-COVID-19 headache between March 2020 and May 2021 were included.
  • Response was measured by the reduction in headache days per month (HDM) from baseline to weeks 8-12.

Main Results:

  • Forty-eight patients were analyzed, with 83.3% being female.
  • A mean reduction of 9.6 HDM was observed.
  • History of TTH and absence of nausea were associated with a higher probability of response to AMT.

Conclusions:

  • Amitriptyline demonstrates potential benefit for managing post-COVID-19 headache in a real-world setting.
  • Patients with a prior history of TTH may particularly benefit from AMT.
  • AMT was generally well-tolerated, with low discontinuation rates due to side effects.