What are the uses of Methysergide (methysergide maleate)?

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From the Guidelines

Methysergide should not be used as a first-line treatment for migraine prevention due to its association with retroperitoneal and retropleural fibrosis, and its use should be limited to patients with severe, refractory migraines who have failed multiple other preventive therapies. The evidence from the American Family Physician guidelines 1 suggests that the usefulness of methysergide is now limited due to its serious side effect profile. The typical dosage of methysergide was 4-8 mg daily, divided into 2-4 doses, but treatment required careful monitoring with drug holidays to reduce the risk of fibrotic complications.

Key Considerations

  • Methysergide is contraindicated in patients with peripheral vascular disease, coronary artery disease, hypertension, peptic ulcer disease, fibrotic disorders, and pregnancy.
  • Newer migraine preventive medications with better safety profiles, such as CGRP antagonists, beta-blockers, anticonvulsants, and certain antidepressants, have largely replaced methysergide in clinical practice.
  • If methysergide is considered, it should only be used under close specialist supervision.

Alternative Treatments

  • CGRP antagonists, beta-blockers, anticonvulsants, and certain antidepressants are preferred for migraine prevention due to their better safety profiles.
  • Feverfew, an herbal remedy, has shown promise in reducing migraine frequency and severity, but more research is needed to confirm its efficacy 1.
  • Magnesium and vitamin B2 (riboflavin) supplements have also shown benefits in some studies, but the evidence is not yet conclusive.

From the FDA Drug Label

Dihydroergotamine mesylate, 5-HT1 agonists (e. g., sumatriptan), ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other. The FDA drug label does not answer the question about methysergide use in general, it only mentions a contraindication related to its concurrent use with other specific medications.

  • Contraindications for methysergide use are not explicitly stated in the provided label, except for the interaction with dihydroergotamine mesylate and other medications.
  • No direct information is available about the use of methysergide alone 2.

From the Research

Methysergide Use

  • Methysergide is a semisynthetic ergot alkaloid ergometrine derivative used for migraine prophylaxis as a specific serotonin (5HT) receptor antagonist 3.
  • It is not just a 5HT2 antagonist, but also a 5HT1 agonist, and has been shown to be effective in open and controlled studies 3.
  • Methysergide may be more effective in resistant cases with a high attack frequency and may act synergistically with ergotamine and dihydroergotamine (DHE) for breakthrough attacks 3.

Contraindications and Side Effects

  • Contraindications for methysergide use include pregnancy, peripheral vascular disorders, severe arteriosclerosis, coronary artery disease, severe hypertension, thrombophlebitis or cellulitis of the legs, peptic ulcer disease, fibrotic disorders, lung diseases, collagen disease, liver or renal function impairment, valvular heart disease, debilitation, or serious infection 3.
  • Methysergide can induce retroperitoneal fibrosis and pleural and heart valve fibrosis with an estimated incidence of 1 in 5,000 treated patients 3.
  • Psychiatric side effects, such as impaired concentration and thought projection, severe anxiety, and depression, have also been reported during methysergide treatment 4.

Clinical Use and Availability

  • Despite safety concerns, a survey among members of the International Headache Society found that 71.3% of respondents had ever prescribed methysergide and 79.8% would prescribe it if it were to become available 5.
  • The survey revealed that respondents used methysergide more in cluster headache than migraine, and reserved it for use in refractory patients 5.
  • The International Headache Society supports the continued availability of methysergide as a unique treatment option for specific populations for which there are no alternatives 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Methysergide.

Cephalalgia : an international journal of headache, 1998

Research

Psychiatric side effects during methysergide treatment.

Journal of neurology, neurosurgery, and psychiatry, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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