Cluster headache therapies: pharmacology and mode of action

References

• Headache classification committee of the International Headache Society (IHS). The international classification of headache disorders. Cephalalgia. 2018;38:1–211. 3rd edition.
   PubMed Web of Science ®Google Scholar
• Dodick D, Rozen T, Goadsby P, et al. Cluster headache. Cephalalgia. 2000;20:787–803.
   PubMed Web of Science ®Google Scholar
• Obermann M, Holle D, Naegel S, et al. Pharmacotherapy options for cluster headache. Expert Opin Pharmacother. 2015;16:1177–1184.
   PubMed Web of Science ®Google Scholar
• Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381:132–141.
   PubMed Web of Science ®Google Scholar
• Manzoni GC, Terzano MG, Bono G, et al. Cluster headache — clinical findings in 180 patients. Cephalalgia. 1983;3:21–30.
   PubMed Web of Science ®Google Scholar
• Martins IP, Gouveia RG, Parreira E. Cluster headache without autonomic symptoms: why is it different? Headache. 2005;45:190–195.
   PubMedGoogle Scholar
• Favier I, Van Vliet JA, Roon KI, et al. Trigeminal autonomic cephalgias due to structural lesions: A review of 31 cases. Arch Neurol. 2007;64:25–31.
   PubMedGoogle Scholar
• Fischera M, Marziniak M, Gralow I, et al. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia. 2008;28:614–618.
   PubMed Web of Science ®Google Scholar
• Ekbom K, Svensson DA, Träff H, et al. Age at onset and sex ratio in cluster headache: observations over three decades. Cephalalgia. 2002;22:94–100.
   PubMed Web of Science ®Google Scholar
• Bahra A, May A, Goadsby PJ. Cluster headache: A prospective clinical study with diagnostic implications. Neurology. 2002;58:354–361.
   PubMed Web of Science ®Google Scholar
• May A, Schwedt TJ, Magis D, et al. Cluster headache. Nat Rev Dis Prim. 2018;4:18006.
   Web of Science ®Google Scholar
• Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol. 2018;17:75–83.
   PubMed Web of Science ®Google Scholar
• Mason RT, Peterfreund RA, Sawchenko PE, et al. Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells. Nature. 1984;308:653–655.
   PubMed Web of Science ®Google Scholar
• Longmore J, Shaw D, Smith D, et al. Differential distribution of 5HT(1D)- and 5HT(1B)-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs. Cephalalgia. 1997;17:833–842.
   PubMed Web of Science ®Google Scholar
• Hou M, Kanje M, Longmore J, et al. 5-HT1B and 5-HT1D receptors in the human trigeminal ganglion: co-localization with calcitonin gene-related peptide, substance P and nitric oxide synthase. Brain Res. 2001;909:112–120.
   PubMed Web of Science ®Google Scholar
• Classey JD, Bartsch T, Goadsby PJ. Distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor expression in rat trigeminal and dorsal root ganglia neurons: relevance to the selective anti-migraine effect of triptans. Brain Res. 2010;1361:76–85.
   PubMed Web of Science ®Google Scholar
• May A, Goadsby PJ. The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab. 1999;19:115–127.
   PubMed Web of Science ®Google Scholar
• Lambert GA, Goadsby PJ, Zagami AS, et al. Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat. Brain Res. 1988;453:143–149.
   PubMed Web of Science ®Google Scholar
• Suzuki N, Hardebo JE, Kahrstrom J, et al. Effect on cortical blood flow of electrical stimulation of trigeminal cerebrovascular nerve fibres in the rat. Acta Physiol Scand. 1990;138:307–315.
   PubMedGoogle Scholar
• Goadsby PJ, Knight YE, Hoskin KL, et al. Stimulation of an intracranial trigeminally-innervated structure selectively increases cerebral blood flow. Brain Res. 1997;751:247–252.
   PubMed Web of Science ®Google Scholar
• Spencer SE, Sawyer WB, Wada H, et al. CNS projections to the pterygopalatine parasympathetic preganglionic neurons in the rat: a retrograde transneuronal viral cell body labeling study. Brain Res. 1990;534:149–169.
   PubMed Web of Science ®Google Scholar
• Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache nEuropeptide changes and effects of acute attacks therapies. Brain. 1994;117:427–434.
   PubMed Web of Science ®Google Scholar
• Fanciullacci M, Alessandri M, Figini M, et al. Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain. 1995;60:119–123.
   PubMed Web of Science ®Google Scholar
• Ottosson A, Edvinsson L. Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia. 1997;17:166–174.
   PubMed Web of Science ®Google Scholar
• Goadsby PJ. Pathophysiology of cluster headache: A trigeminal autonomic cephalgia. Lancet Neurol. 2002;1:251–257.
   PubMed Web of Science ®Google Scholar
• Edvardsson B. Symptomatic cluster headache: A review of 63 cases. Springerplus. 2014;3:1–8.
   PubMedGoogle Scholar
• Leone M, Bussone G. A review of hormonal findings in cluster headache. Evidence for hypothalamic involvement. Cephalalgia. 1993;13:309–317.
   PubMed Web of Science ®Google Scholar
• Leone M, Lucini V, Damico D, et al. Abnormal 24hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache. Headache Q. 1999;10:157.
   Google Scholar
• Waldenlind E, Gustafsson SA, Ekbom K, et al. Circadian secretion of cortisol and melatonin in cluster headache during active cluster periods and remission. J Neurol Neurosurg Psychiatry. 1987;50:207–213.
   PubMed Web of Science ®Google Scholar
• Waldenlind E, Ekbom K, Wetterberg L, et al. Lowered circannual urinary melatonin concentrations in episodic cluster headache. Cephalalgia. 1994;14:199–204.
   PubMed Web of Science ®Google Scholar
• Barloese M, Jennum P, Lund N, et al. Reduced CSF hypocretin-1 levels are associated with cluster headache. Cephalalgia. 2015;35:869–876.
   PubMed Web of Science ®Google Scholar
• May A, Bahra A, Büchel C, et al. Hypothalamic activation in cluster headache attacks. Lancet. 1998;352:275–278.
   PubMed Web of Science ®Google Scholar
• Schoenen J, Di Clemente L, Vandenheede M, et al. Hypothalamic stimulation in chronic cluster headache: A pilot study of efficacy and mode of action. Brain. 2005;128:940–947.
   PubMed Web of Science ®Google Scholar
• Leone M, Franzini A, Broggi G, et al. Hypothalamic stimulation for intractable cluster headache: long-term experience. Neurology. 2006;67:150–152.
   PubMed Web of Science ®Google Scholar
• Leone M, Proietti Cecchini A. Deep brain stimulation in headache. Cephalalgia. 2016;36:1143–1148.
   PubMed Web of Science ®Google Scholar
• Vyas DB, Ho AL, Dadey DY, et al. Deep brain stimulation for chronic cluster headache: a review. Neuromodulation. 2019;22:388–397.
   PubMed Web of Science ®Google Scholar
• Leone M, Franzini A, Broggi G, et al. Acute hypothalamic stimulation and ongoing cluster headache attacks. Neurology. 2006;67:1844–1845.
   PubMed Web of Science ®Google Scholar
• Vollesen ALH, Snoer A, Beske RP, et al. Effect of infusion of calcitonin gene-related peptide on cluster headache attacks: a randomized clinical trial. JAMA Neurol. 2018;75:1187–1197.
   PubMed Web of Science ®Google Scholar
• Zagami AS, Edvinsson L, Goadsby PJ. Pituitary adenylate cyclase activating polypeptide and migraine. Ann Clin Transl Neurol. 2014;1:1036–1040.
   PubMed Web of Science ®Google Scholar
• Tuka B, Szabó N, Tóth E, et al. Release of PACAP-38 in episodic cluster headache patients - An exploratory study. J Headache Pain. 2016;17:69.
   Web of Science ®Google Scholar
• Uddman R, Tajti J, Hou M, et al. Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2. Cephalalgia. 2002;22:112–116.
   PubMed Web of Science ®Google Scholar
• Csati A, Tajti J, Kuris A, et al. Distribution of vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, nitric oxide synthase, and their receptors in human and rat sphenopalatine ganglion. Neuroscience. 2012;202:158–168.
   PubMed Web of Science ®Google Scholar
• Robert C, Bourgeais L, Arreto CD, et al. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci. 2013;33:8827–8840.
   PubMed Web of Science ®Google Scholar
• Lambru G, Chan C, Matharu M. Post-traumatic cluster headache: a clinical phenotype study of 16 patients. J Headache Pain. 2013;14:46.
   Web of Science ®Google Scholar
• Robbins MS, Starling AJ, Pringsheim TM, et al. Treatment of cluster headache: the american headache society evidence-based guidelines. Headache. 2016;56:1093–1106.
   PubMed Web of Science ®Google Scholar
• May A, Leone M, Áfra J, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol. 2006;13:1066–1077.
   PubMed Web of Science ®Google Scholar
• Kawamura J, Meyer JS, Terayama Y, et al. Cerebral hyperemia during spontaneous cluster headaches with excessive cerebral vasoconstriction to hyperoxia. Headache J Head Face Pain. 1991;31:222–227.
   PubMed Web of Science ®Google Scholar
• Drummond PD, Anthony M. Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache J Head Face Pain. 1985;25:070–074.
   PubMed Web of Science ®Google Scholar
• Schuh-Hofer S, Siekmann W, Offenhauser N, et al. Effect of hyperoxia on neurogenic plasma protein extravasation in the rat dura mater. Headache. 2006;46:1545–1551.
   PubMed Web of Science ®Google Scholar
• Akerman S, Holland PR, Lasalandra MP, et al. Oxygen inhibits neuronal activation in the trigeminocervical complex after stimulation of trigeminal autonomic reflex, but not during direct dural activation of trigeminal afferents: harold g. wolff lecture award winner. Headache. 2009;49:1131–1143.
   PubMed Web of Science ®Google Scholar
• Jürgens TP, Schulte LH, May A. Oxygen treatment is effective in migraine with autonomic symptoms. Cephalalgia. 2013;33:65–67.
   PubMed Web of Science ®Google Scholar
• Evers S, Rapoport A. The use of oxygen in cluster headache treatment worldwide – A survey of the international headache society (IHS). Cephalalgia. 2017;37:396–398.
   PubMed Web of Science ®Google Scholar
• Pearson SM, Burish MJ, Shapiro RE, et al. Effectiveness of oxygen and other acute treatments for cluster headache: results from the cluster headache questionnaire, an international survey. Headache. 2019;59:235–249.
   PubMed Web of Science ®Google Scholar
• Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: A randomized trial. JAMA. 2009;302:2451–2457.
   PubMed Web of Science ®Google Scholar
• Kudrow L. Response of cluster headache attacks to oxygen inhalation. Headache J Head Face Pain. 1981;21:1–4.
   PubMed Web of Science ®Google Scholar
• Dirkx THT, Haane DYP, Koehler PJ. Oxygen treatment for cluster headache attacks at different flow rates: A double-blind, randomized, crossover study. J Headache Pain. 2018;19:94.
   Web of Science ®Google Scholar
• Rozen TD. High oxygen flow rates for cluster headache. Neurology. 2004;63:593.
   PubMed Web of Science ®Google Scholar
• Petersen AS, Barloese MCJ, Lund NLT, et al. Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study. Cephalalgia. 2017;37:214–224.
   PubMed Web of Science ®Google Scholar
• Goadsby PJ. The pharmacology of headache. Prog Neurobiol. 2000;62:509–525.
   PubMed Web of Science ®Google Scholar
• Longmore J, Razzaque Z, Shaw D, et al. Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT(1B)-receptors. Br J Clin Pharmacol. 1998;46:577–582.
   PubMed Web of Science ®Google Scholar
• Nilsson T, Longmore J, Shaw D, et al. Contractile 5-HT(1B) receptors in human cerebral arteries: pharmacological characterization and localization with immunocytochemistry. Br J Pharmacol. 1999;128:1133–1140.
   PubMed Web of Science ®Google Scholar
• Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol. 1993;33:48–56.
   PubMed Web of Science ®Google Scholar
• Buzzi MG, Moskowitz MA. Evidence for 5-HT1B/1D receptors mediating the antimigraine effect of sumatriptan and dihydroergotamine. Cephalalgia. 1991;11:165–168.
   PubMed Web of Science ®Google Scholar
• Johnson KW, Schaus JM, Durkin MM, et al. 5-HT(1F) receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Neuroreport. 1997;8:2237–2240.
   PubMed Web of Science ®Google Scholar
• Bartsch T, Knight YE, Goadsby PJ. Activation of 5-HT1B/1D receptor in the periaqueductal gray inhibits nociception. Ann Neurol. 2004;56:371–381.
   PubMed Web of Science ®Google Scholar
• Hoskin KL, Goadsby PJ. Comparison of more and less lipophilic serotonin (5HT(1B/1D)) agonists in a model of trigeminovascular nociception in cat. Exp Neurol. 1998;150:45–51.
   PubMed Web of Science ®Google Scholar
• Pascual J, Muñoz P. Correlation between lipophilicity and triptan outcomes. Headache. 2005;45:3–6.
   PubMed Web of Science ®Google Scholar
• Tfelt-Hansen PC. Does sumatriptan cross the blood-brain barrier in animals and man? J Headache Pain. 2010;11:5–12.
   PubMed Web of Science ®Google Scholar
• The sumatriptan cluster headache study group. Treatment of acute cluster headache with sumatriptan. N Engl J Med. 1991;325:322–326.
   PubMed Web of Science ®Google Scholar
• Ekbom K, Monstad I, Prusinski A, et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. Acta Neurol Scand. 1993;88:63–69.
   PubMed Web of Science ®Google Scholar
• Law S, Derry S, Moore RA. Triptans for acute cluster headache. Cochrane Database Syst Rev. 2013;2013(7):CD008042.
   Web of Science ®Google Scholar
• Van Vliet JA, Bahra A, Martin V, et al. Intranasal sumatriptan in cluster headache: randomized placebo-controlled double-blind study. Neurology. 2003;60:630–633.
   PubMed Web of Science ®Google Scholar
• Rapoport AM, Mathew NT, Silberstein SD, et al. Zolmitriptan nasal spray in the acute treatment of cluster headache: A double-blind study. Neurology. 2007;69:821–826.
   PubMed Web of Science ®Google Scholar
• Cittadini E, May A, Straube A, et al. Effectiveness of intranasal zolmitriptan in acute cluster headache: A randomized, placebo-controlled, double-blind crossover study. Arch Neurol. 2006;63:1537–1542.
   PubMed Web of Science ®Google Scholar
• Göbel H, Lindner V, Heinze A, et al. Acute therapy for cluster headache with sumatriptan: findings of a one- year long-term study. Neurology. 1998;51:908–911.
   PubMed Web of Science ®Google Scholar
• Nelson DL, Phebus LA, Johnson KW, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia. 2010;30:1159–1169.
   PubMed Web of Science ®Google Scholar
• Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, et al. Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan. Br J Pharmacol. 2019;176:4681–4695.
   PubMed Web of Science ®Google Scholar
• Labastida-Ramírez A, Rubio-Beltrán E, Haanes KA, et al. Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system. Pain. 2020;161:1092–1099.
   PubMed Web of Science ®Google Scholar
• Pageler L, Limmroth V. Oral triptans in the preventive management of cluster headache. Curr Pain Headache Rep. 2012;16:180–184.
   PubMed Web of Science ®Google Scholar
• Catterall WA. Molecular mechanisms of gating and drug block of sodium channels. Novartis Found Symp. 2002;241:206–225.
   PubMed Web of Science ®Google Scholar
• Kittrelle JP, Grouse DS, Seybold ME. Cluster headache: local anesthetic abortive agents. Arch Neurol. 1985;42:496–498.
   PubMedGoogle Scholar
• Robbins L. Intranasal lidocaine for cluster headache. Headache J Head Face Pain. 1995;35:83–84.
   PubMed Web of Science ®Google Scholar
• Costa A, Pucci E, Antonaci F, et al. The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache. Cephalalgia. 2000;20:85–91.
   PubMed Web of Science ®Google Scholar
• Morgan A, Jessop V. Bet 2: should intranasal lidocaine be used in patients with acute cluster headache? Emerg Med J. 2013;30:769–770.
   PubMed Web of Science ®Google Scholar
• Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache J Head Face Pain. 2003;43:144–166.
   PubMed Web of Science ®Google Scholar
• Dahlöf C, Maassen Van Den Brink A. Dihydroergotamine, ergotamine, methysergide and sumatriptan - Basic science in relation to migraine treatment. Headache. 2012;52:707–714.
   PubMed Web of Science ®Google Scholar
• Ekbom KA. Ergotamine tartrate orally in Horton’s “histaminic cephalgia” (also called Harris’s “ciliary neuralgia”): A new method of treatment. Acta Psychiatr Scand. 1947;22:105–113.
   Google Scholar
• Silberstein SD, Shrewsbury SB, Hoekman J. Dihydroergotamine (DHE) – then and now: a narrative review. Headache. 2020;60:40–57.
   PubMed Web of Science ®Google Scholar
• Andersson PG, Jespersen LT. Dihydroergotamine nasal spray in the treatment of attacks of cluster headache. A double-blind trial versus placebo. Cephalalgia. 1986;6:51–54.
   PubMed Web of Science ®Google Scholar
• Mather PJ, Silberstein SD, Schulman EA, et al. The treatment of cluster headache with repetitive intravenous dihydroergotamine. Headache J Head Face Pain. 1991;31:525–532.
   PubMed Web of Science ®Google Scholar
• Magnoux E, Zlotnik G. Outpatient intravenous dihydroergotamine for refractory cluster headache. Headache. 2004;44:249–255.
   PubMed Web of Science ®Google Scholar
• Nagy AJ, Gandhi S, Bhola R, et al. Intravenous dihydroergotamine for inpatient management of refractory primary headaches. Neurology. 2011;77:1827–1832.
   PubMed Web of Science ®Google Scholar
• Lipton RB. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache. 1997;37(Suppl 1):S33–41.
   PubMed Web of Science ®Google Scholar
• Saper JR, Silberstein S. Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine. Headache J Head Face Pain. 2006;46:S171–S181.
   PubMed Web of Science ®Google Scholar
• Harris AG. Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. Gut. 1994;35:1–4.
   Web of Science ®Google Scholar
• Hofland LJ, Lamberts SWJ. Somatostatin receptors and disease: role of receptor subtypes. Baillieres Clin Endocrinol Metab. 1996;10:163–176.
   PubMed Web of Science ®Google Scholar
• Bereiter DA. Morphine and somatostatin analogue reduce c-fos expression in trigeminal subnucleus caudalis produced by corneal stimulation in the rat. Neuroscience. 1997;77:863–874.
   PubMed Web of Science ®Google Scholar
• Bartsch T, Levy MJ, Knight YE, et al. Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus. Pain. 2005;117:30–39.
   PubMed Web of Science ®Google Scholar
• Chapman V, Dickenson AH. The effects of sandostatin and somatostatin on nociceptive transmission in the dorsal horn of the rat spinal cord. Neuropeptides. 1992;23:147–152.
   PubMed Web of Science ®Google Scholar
• Helyes Z, Pintér E, Németh J, et al. Anti-inflammatory effect of synthetic somatostatin analogues in the rat. Br J Pharmacol. 2001;134:1571–1579.
   PubMed Web of Science ®Google Scholar
• Fassler JE, O’Dorisio TM, Mekhjian HS, et al. Octreotide inhibits increases in short-circuit current induced in rat colon by VIP, substance P, serotonin and aminophylline. Regul Pept. 1990;29:189–197.
   PubMedGoogle Scholar
• Sicuteri F, Geppetti P, Marabini S, et al. Pain relief by somatostatin in attacks of cluster headache. Pain. 1984;18:359–365.
   PubMed Web of Science ®Google Scholar
• Matharu MS, Levy MJ, Meeran K, et al. Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Ann Neurol. 2004;56:488–494.
   PubMed Web of Science ®Google Scholar
• Safety and efficacy study of som230 s.c. in cluster headache - study results - clinicalTrials.gov. [ cited 2020 Mar 1]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT02619617
   Google Scholar
• Striessnig J, Pinggera A, Kaur G, et al. L-type Ca2+ channels in heart and brain. Wiley Interdiscip Rev Membr Transp Signal. 2014;3:15–38.
   PubMedGoogle Scholar
• Petersen AS, Barloese MCJ, Snoer A, et al. Verapamil and cluster headache: still a mystery. a narrative review of efficacy, mechanisms and perspectives. Headache. 2019;59:1198–1211.
   PubMed Web of Science ®Google Scholar
• Akerman S, Williamson DJ, Goadsby PJ. Voltage-dependent calcium channels are involved in neurogenic dural vasodilatation via a presynaptic transmitter release mechanism. Br J Pharmacol. 2003;140:558–566.
   PubMed Web of Science ®Google Scholar
• Amrutkar DV, Ploug KB, Olesen J, et al. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system. Neuroscience. 2011;172:510–517.
   PubMed Web of Science ®Google Scholar
• Leone M, D’Amico D, Frediani F, et al. Verapamil in the prophylaxis of episodic cluster headache: A double- blind study versus placebo. Neurology. 2000;54:1382–1385.
   PubMed Web of Science ®Google Scholar
• Hardebo JE. How Cluster Headache is Explained as an Intracavernous Inflammatory Process Lesioning Sympathetic Fibers. Headache J Head Face Pain. 1994;34:125–131.
   PubMed Web of Science ®Google Scholar
• Hannerz J. Orbital phlebography and signs of inflammation in episodic and chronic cluster headache. Headache J Head Face Pain. 1991;31:540–542.
   PubMed Web of Science ®Google Scholar
• Neeb L, Hellen P, Hoffmann J, et al. Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells. J Headache Pain. 2016;17:1–6.
   Web of Science ®Google Scholar
• Neeb L, Anders L, Euskirchen P, et al. Corticosteroids alter CGRP and melatonin release in cluster headache episodes. Cephalalgia. 2015;35:317–326.
   PubMed Web of Science ®Google Scholar
• Couch JR, Ziegler DK. Prednisone therapy for cluster headache. Headache J Head Face Pain. 1978;18:219–221.
   PubMed Web of Science ®Google Scholar
• Mir P, Alberca R, Navarro A, et al. Prophylactic treatment of episodic cluster headache with intravenous bolus of methylprednisolone. Neurol Sci. 2003;24:318–321.
   PubMed Web of Science ®Google Scholar
• Ekbom K. Lithium in the treatment of chronic cluster headache. Headache J Head Face Pain. 1977;17:39–40.
   PubMed Web of Science ®Google Scholar
• Kudrow L. Lithium prophylaxis for chronic cluster headache. Headache J Head Face Pain. 1977;17:15–18.
   PubMed Web of Science ®Google Scholar
• Alda M. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry Nature Publish Group. 2015;20:661–670.
   Google Scholar
• Steiner TJ, Hering R, Couturier EGM, et al. Double-blind placebo-controlled trial of lithium in episodic cluster headache. Cephalalgia. 1997;17:673–675.
   PubMed Web of Science ®Google Scholar
• Nugent AC, Carlson PJ, Bain EE, et al. Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression. J Psychopharmacol. 2013;27:894–902.
   PubMed Web of Science ®Google Scholar
• Blier P, De Montigny C, Tardif D. Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT1A receptors without altering 5‐HT autoreceptor sensitivity: an electrophysiological study in the rat brain. Synapse. 1987;1:225–232.
   PubMed Web of Science ®Google Scholar
• Redrobe JP, Bourin M. Evidence of the activity of lithium on 5-HT(1B) receptors in the mouse forced swimming test: comparison with carbamazepine and sodium valproate. Psychopharmacology (Berl). 1999;141:370–377.
   PubMed Web of Science ®Google Scholar
• Klemfuss H. Rhythms and the pharmacology of lithium. Pharmacol Ther. 1992;56:53–78.
   PubMed Web of Science ®Google Scholar
• Chazot G, Claustrat B, Brun J, et al. Effects on the patterns of melatonin and cortisol in cluster headache of a single administration of lithium at 7.00 p.m. daily over one week: A preliminary report. Pharmacopsychiatry. 1987;20:222–223.
   PubMed Web of Science ®Google Scholar
• Ekbom K. Lithium for cluster headache: review of the literature and preliminary results of long‐term treatment. Headache J Head Face Pain. 1981;21:132–139.
   PubMed Web of Science ®Google Scholar
• Stochino ME, Deidda A, Asuni C, et al. Evaluation of lithium response in episodic cluster headache: A retrospective case series. Headache. 2012;52:1171–1175.
   PubMed Web of Science ®Google Scholar
• Bussone G, Leone M, Peccarisi C, et al. Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache J Head Face Pain. 1990;30:411–417.
   PubMed Web of Science ®Google Scholar
• Ashkenazi A, Schwedt T. Cluster headache-acute and prophylactic therapy. Headache. 2011;51:272–286.
   PubMed Web of Science ®Google Scholar
• Shank RP, Maryanoff BE. Molecular pharmacodynamics, clinical therapeutics, and pharmacokinetics of topiramate. CNS Neurosci Ther. 2008;14:120–142.
   PubMed Web of Science ®Google Scholar
• Hoffmann J, Akerman S, Goadsby PJ. Efficacy and mechanism of anticonvulsant drugs in migraine. Expert Rev Clin Pharmacol. 2014;7:191–201.
   PubMed Web of Science ®Google Scholar
• Storer RJ, Goadsby PJ. Topiramate inhibits trigeminovascular neurons in the cat. Cephalalgia. 2004;24:1049–1056.
   PubMed Web of Science ®Google Scholar
• Storer RJ, Goadsby PJ. Topiramate is likely to act outside of the trigeminocervical complex. Cephalalgia. 2013;33:291–300.
   PubMed Web of Science ®Google Scholar
• Durham PL, Niemann C, Cady R. Repression of stimulated calcitonin gene-related peptide secretion by topiramate. Headache. 2006;46:1291–1295.
   PubMed Web of Science ®Google Scholar
• Wheeler SD, Carrazana EJ. Topiramate-treated cluster headache. Neurology. 1999;53:234–236.
   PubMed Web of Science ®Google Scholar
• Láinez MJA, Pascual J, Pascual AM, et al. Topiramate in the prophylactic treatment of cluster headache. Headache. 2003;43:784–789.
   PubMed Web of Science ®Google Scholar
• Leone M, Dodick D, Rigamonti A, et al. Topiramate in cluster headache prophylaxis: an open trial. Cephalalgia. 2003;23:1001–1002.
   PubMed Web of Science ®Google Scholar
• Hering R, Kuritzky A. Sodium valproate in the treatment of cluster headache: an open clinical trial. Cephalalgia. 1989;9:195–198.
   PubMed Web of Science ®Google Scholar
• El Amrani M, Massiou H, Bousser MG. A negative trial of sodium valproate in cluster headache: methodological issues. Cephalalgia. 2002;22:205–208.
   PubMed Web of Science ®Google Scholar
• Leandri M, Luzzani M, Cruccu G, et al. Drug-resistant cluster headache responding to gabapentin: A pilot study. Cephalalgia. 2001;21:744–746.
   PubMed Web of Science ®Google Scholar
• Schuh-Hofer S, Israel H, Neeb L, et al. The use of gabapentin in chronic cluster headache patients refractory to first-line therapy. Eur J Neurol. 2007;14:694–696.
   PubMed Web of Science ®Google Scholar
• Vuković V, Lovrencić-Huzjan A, Budisić M, et al. Gabapentin in the prophylaxis of cluster headache: an observational open label study. Acta Clin Croat. 2009;48:311–314.
   PubMed Web of Science ®Google Scholar
• Sharma SK, Vij AS, Sharma M. Mechanisms and clinical uses of capsaicin. Eur J Pharmacol. 2013;720:55–62.
   PubMed Web of Science ®Google Scholar
• Sałat K, Jakubowska A, Kulig K. Zucapsaicin for the treatment of neuropathic pain. Expert Opin Investig Drugs. 2014;23:1433–1440.
   PubMed Web of Science ®Google Scholar
• Marks DR, Rapoport A, Padla D, et al. A double-blind placebo-controlled trial of intranasal capsaicin for cluster headache. Cephalalgia. 1993;13:114–116.
   PubMed Web of Science ®Google Scholar
• Saper JR, Klapper J, Mathew NT, et al. Intranasal civamide for the treatment of episodic cluster headaches. Arch Neurol. 2002;59:990–994.
   PubMed Web of Science ®Google Scholar
• Intranasal civamide for episodic cluster headache - full text view - clinicaltrials.gov. [ cited 2020 Feb 4]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00069082
   Google Scholar
• Speight TM, Avery GS. Pizotifen(BC-105): a review of its pharmacological properties and its therapeutic efficacy in vascular headaches. Drugs. 1972;3:159–203. [cited 2020 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4403890
   PubMed Web of Science ®Google Scholar
• Ekbom K. Prophylactic treatment of cluster headache with a new serotonin antagonist, BC 105. Acta Neurol Scand. 1969;45:601–610.
   PubMed Web of Science ®Google Scholar
• Reppert SM, Perlow MJ, Ungerleider LG, et al. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey. J Neurosci. 1981;1:1414–1425.
   PubMed Web of Science ®Google Scholar
• Bedrosian TA, Herring KL, Walton JC, et al. Evidence for feedback control of pineal melatonin secretion. Neurosci Lett. 2013;542:123–125.
   PubMed Web of Science ®Google Scholar
• Pringsheim T, Magnoux E, Dobson CF, et al. Melatonin as adjunctive therapy in the prophylaxis of cluster headache: A pilot study. Headache. 2002;42:787–792.
   PubMed Web of Science ®Google Scholar
• Golombek DA, PéVet P, Cardinali DP. Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev. 1996;20:403–412.
   PubMed Web of Science ®Google Scholar
• Leone M, D’Amico D, Moschiano F, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16:494–496.
   PubMed Web of Science ®Google Scholar
• Silberstein SD. Methysergide. Cephalalgia. 1998;18:421–435.
   PubMed Web of Science ®Google Scholar
• Bartsch T. Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain. 2002;125:1496–1509.
   PubMed Web of Science ®Google Scholar
• Bartsch T, Goadsby PJ. Increased responses in trigeminocervical nociceptive neurons to cervical input after stimulation of the dura mater. Brain. 2003;126:1801–1813.
   PubMed Web of Science ®Google Scholar
• Ambrosini A, Vandenheede M, Rossi P, et al. Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: A double-blind placebo-controlled study. Pain. 2005;118:92–96.
   PubMed Web of Science ®Google Scholar
• Leroux E, Valade D, Taifas I, 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;10:891–897.
   PubMed Web of Science ®Google Scholar
• Ramachandran R, Yaksh TL. Therapeutic use of botulinum toxin in migraine: mechanisms of action. Br J Pharmacol. 2014;171:4177–4192.
   PubMed Web of Science ®Google Scholar
• Meng J, Wang J, Lawrence G, et al. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cell Sci. 2007;120:2864–2874.
   PubMed Web of Science ®Google Scholar
• Lackovic Z, Filipovic B, Matak I, et al. Activity of botulinum toxin type A in cranial dura: implications for treatment of migraine and other headaches. Br J Pharmacol. 2016;173:279–291.
   PubMed Web of Science ®Google Scholar
• Sostak P, Krause P, Förderreuther S, et al. Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain. 2007;8:236–241.
   PubMed Web of Science ®Google Scholar
• Lampl C, Rudolph M, Bräutigam E. OnabotulinumtoxinA in the treatment of refractory chronic cluster headache. J Headache Pain. 2018;19:45.
   Web of Science ®Google Scholar
• Bratbak DF, Nordgård S, Stovner LJ, et al. Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic cluster headache. Cephalalgia. 2015;36:503–509.
   PubMed Web of Science ®Google Scholar
• Raffaelli B, Reuter U. The biology of monoclonal antibodies: focus on calcitonin gene-related peptide for prophylactic migraine therapy. Neurotherapeutics. 2018;15:324–335. [cited 2020 May 5]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29616494
   PubMed Web of Science ®Google Scholar
• Dodick DW, Goadsby PJ, Lucas C, et al. Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: results from 3-month double-blind treatment. Cephalalgia. 2020;0:033310242090532.
   Web of Science ®Google Scholar
• A Study Comparing the efficacy and safety of fremanezumab (TEV-48125) for the prevention of chronic cluster headache (CCH) - full text view - clinicaltrials.gov. [ cited 2020 Feb 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02964338
   Google Scholar
• A study to evaluate the efficacy and safety of TEV-48125 (Fremanezumab) for the prevention of Episodic Cluster Headache (ECH) - full text view - clinicaltrials.gov. [ cited 2020 Feb 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02945046
   Google Scholar
• Snoer A, Vollesen ALH, Beske RP, et al. Calcitonin-gene related peptide and disease activity in cluster headache. Cephalalgia. 2019;39:575–584.
   PubMed Web of Science ®Google Scholar