Intravenous methylprednisolone in patients with episodic cluster headache non-responders to oral steroids: results from an observational, interventional, single-center study

Submitted: 15 January 2024
Accepted: 19 May 2024
Published: 18 June 2024
Abstract Views: 496
PDF: 176
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


Background: Verapamil is the drug of choice in the prophylaxis of episodic cluster headache (ECH), and oral corticosteroids are frequently prescribed as concurrent bridging therapy. Approximately 25% of the patients do not respond to oral treatment. The aim of this study was to assess safety and efficacy of high dose intravenous methylprednisolone (MPD) in ECH patients who had not responded to combined oral therapy with prednisone and verapamil.
Methods: Forty-four ECH patients – non responders to oral therapy – were treated with intravenous MPD (500 mg/day for 5 days) and verapamil during cluster headache active periods. No serious adverse event was reported.
Results: After 5 days of intravenous therapy, the 24-hour frequency of cluster headache attacks significantly decreased. Sixty-eight percent of patients became headache-free, and 25% experienced a reduction of more than 50% in daily attacks. No clinical benefit was reported in the remaining three patients.
Conclusions: Our study shows that intravenous MPD is a safe, effective, and reproducible treatment for ECH patients not responding to oral therapy.



PlumX Metrics


Download data is not yet available.


Russell MB. Epidemiology and genetics of cluster headache. Lancet Neurol 2004;3:279-283. DOI:
Gaul C, Finken J, Biermann J, Mostardt S, Diener HC, Müller O, et al. Treatment costs and indirect costs of cluster headache: a health economics analysis. Cephalalgia 2011;31:1664-72. DOI:
Sarchielli P, Granella F, Prudenzano MP, Pini LA, Guidetti V, Bono G, et al. Italian guidelines for primary headaches: 2012 revised version. J Headache Pain 2012;13:S31-70.
May A, Leone M, Afra J, Linde M, Sándor PS, Evers S, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol 2006;13: 1066-77. DOI:
Robbins MS, Starling AJ, Pringsheim T, Becker WJ, Schwedt TJ. Treatment of cluster headache: the American Headache Society Evidence‐Based Guidelines. Headache 2016;56:1093-106. DOI:
Evers S. Pharmacotherapy of cluster headache. Expert Opin Pharmacother 2010;11:2121-7. DOI:
Leone M, D’Amico D, Frediani F, Moschiano F, Grazzi L, Attanasio A, Bussone G. Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo. Neurology 2000;54:1382-5. DOI:
May A, Schwedt TJ, Magis D, Pozo‐Rosich P, Evers S, Wang SJ. Cluster headache. Nat Rev Dis Primers 2018;4:18006. DOI:
Ambrosini A, Vandenheede M, Rossi P, Aloj F, Sauli E, Pierelli F, et al. Suboccipital injection with a mixture of rapid- and longacting steroids in cluster headache: a double-blind placebocontrolled study. Pain 2005;118:92-6. DOI:
Leroux E, Valade D, Taifas I, Vicaut É, Chagnon M, Roos C, et al. Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2011;10:891-7. DOI:
Obermann M, Nägel S, Ose C, Sonuc N, Scherag A, Storch P, et al. Safety and efficacy of prednisone versus placebo in shortterm prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial. Lancet Neurol 2021;20:29-37. DOI:
Cianchetti C, Zudeas A, Marchei F. High-dose intravenous methylprednisolone in cluster headache. J Neurol Neurosurg Psych 1998;64:418. DOI:
Mir P, Alberca R, Navarro A, Montes E, Martínez E, Franco E, et al. Prophylactic treatment of episodic cluster headache with intravenous bolus of methylprednisolone. Neurol Sci 2003;24:318-21. DOI:
Antonaci F, Costa A, Candeloro E, Sjaastad O, Nappi G. Single high-dose steroid treatment in episodic cluster headache. Cephalalgia 2005;25:290-5. DOI:
Zanchin G, Disco C, Mainardi F, Mampreso E, Lisotto C, Maggioni F. High-dose of methylprednisolone and verapamil in chronic cluster headache: a case report. J Headache Pain 2012; 13:S26.
Kawada S, Kashihara K, Imamura T, Ohno O. High-dose intravenous methylprednisolone for the prophylactic treatment of cluster headache. Springerplus 2013;2:156. DOI:
May A, Evers S, Goadsby PJ, Leone M, Manzoni GC, Pascual J, et al. European Academy of Neurology guidelines on the treatment of cluster headache. Eur J Neurol 2023;30:2955-79. DOI:
Ramamoorthy S, Cidlowski JA. Corticosteroids. Rheum Dis Clin N Am 2016;42:15-31. DOI:
Klehmet J, Staudt M, Ulm L, Unterwalder N, Meisel A, Meisel C. Circulating lymphocyte and T memory subsets in
glucocorticosteroid versus IVIG treated patients with CIDP. J Neuroimmunol 2015;283:17-22.
Neeb L, Anders L, Euskirchen P, et al. Corticosteroids alter CGRP and melatonin release in cluster headache episodes. Cephalalgia 2015;35:317-326. DOI:
Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004;24:160.
Olesen, J. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1-211. DOI:

How to Cite

Rubino E, Roveta F, Marcinnò A, Ferrandes F, Piella EM, Rainero I. Intravenous methylprednisolone in patients with episodic cluster headache non-responders to oral steroids: results from an observational, interventional, single-center study. Confinia Cephalal [Internet]. 2024 Jun. 18 [cited 2024 Jul. 25];34(1). Available from: