Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 8165  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
  » Next article
  » Previous article 
  » Table of Contents
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (297 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  Abstract
 »  Introduction
 »  Materials and Me...
 »  Results
 »  Discussion
 »  References
 »  Article Tables

 Article Access Statistics
    PDF Downloaded151    
    Comments [Add]    
    Cited by others 12    

Recommend this journal


Year : 2010  |  Volume : 58  |  Issue : 2  |  Page : 284-287

Topiramate in prevention of cluster headache in the Taiwanese

1 Neuroscience & Psychiatry Research Lab, Changhua Christian Hospital, Changhua; and Department of Pediatrics, Kuang-Tein General Hospital, Taipei, Taiwan
2 Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
3 Neurologial Institute, Taipei Veterans General Hospital, Taipei, Taiwan
4 Department of Neurology, National Cheng-Kung University Hospital, Tainan, Taiwan
5 Neuroscience & Psychiatry Research Lab, Changhua Christian Hospital, Changhua; Department of Neurology, Changhua Christian Hospital, Changhua; and Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan

Date of Acceptance01-Feb-2010
Date of Web Publication26-May-2010

Correspondence Address:
H M Wu
Department of Neurology, Changhua Christian Hospital, 135 Nanxiao St. Changhua City, Changhua
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.63784

Rights and Permissions

 » Abstract 

Topiramate could potentially effective as prophylaxis for cluster headache, but the experience remains limited in Asians. We performed an open-label clinical study to evaluate the efficacy of topiramate in the tolerable dosage to prevent cluster headache. We studied patients who fulfilled the criteria of episodic or chronic cluster headaches (International Classification of Headache Disorders second edition) prospectively. Headache severity was assessed using a verbal rating scale (excruciating, severe, moderate, mild, and no headache). Treatment was started with a topiramate dose of 50 mg twice daily and was increased by 50-100 mg a day every 3 to 7 days as tolerated to a maximal daily dosage of 400 mg. Of the 12 patients with episodic cluster headache, nine patients had remission of headache at a mean daily dosage of 273 mg (range 100-400 mg ), and the patient with chronic cluster headache had remission at a daily dosage of 400 mg. The adverse effects included: paresthesia (84%), slow speech (54%), and dizziness (46%), but were tolerated by most patients. Two patients discontinued topiramate due to adverse events and one due to lack of efficacy. This open-label study suggests that topiramate is effective in the treatment of cluster headache in Taiwanese patients.

Keywords: Anticonvulsant, cluster headache, chronic cluster headache, topiramate

How to cite this article:
Huang W Y, Lo M C, Wang S J, Tsai J J, Wu H M. Topiramate in prevention of cluster headache in the Taiwanese. Neurol India 2010;58:284-7

How to cite this URL:
Huang W Y, Lo M C, Wang S J, Tsai J J, Wu H M. Topiramate in prevention of cluster headache in the Taiwanese. Neurol India [serial online] 2010 [cited 2022 Aug 14];58:284-7. Available from: https://www.neurologyindia.com/text.asp?2010/58/2/284/63784

 » Introduction Top

Cluster headache is one of the most severe forms of head pain and is distinct from other forms of headache in terms of clinical features and management. [1] Cluster headache is characterized by periodicity, typically one or two cluster periods a year, with each one lasting two to three months. [2],[3] The sufferers usually experience moderate to severe disability, which may lead to decreased productivity and job loss. Recently, a few clinical studies have shown the effectiveness of topiramate in the prophylaxis of cluster headache, [4],[5],[6],[7],[8] however, the experience in Asians is still limited. We performed an open-label trial to evaluate the efficacy of topiramate at the tolerable dose in the prevention of cluster headache.

 » Materials and Methods Top

Thirteen patients who fulfilled the criteria of episodic (n=12) or chronic (n=1) cluster headache of the International Classification of Headache Disorders second edition (ICHD-II) [2] were studied prospectively. In all the patients demographic data, medical history, and headache profile were recorded. Non-contrast magnetic resonance imaging (MRI) of brain was normal in all the patients. The patient with chronic cluster headache and three patients with episodic cluster headache were being treated with traditional preventive treatment such as non-steroid anti-inflammatory drug and verapamil, but with no effect. Topiramate treatment started at a dosage of 50 mg twice daily. The daily dose was increased by 50-100 mg every three to seven days as tolerated, with a maximum dose of 400 mg/day. Headache severity was assessed using a five-point verbal rating scale (excruciating, severe, moderate, mild, and no headache). [9] All participants were trained on how to rate their pain and record headache diaries. Remission was defined as having no headache for at least three days. After a remission period of over two weeks, the daily dose was reduced by 50 mg every three to seven days in patients with episodic cluster headache. The Hospital Ethics Committee has approved the study according to the Helsinki rules and informed consent was obtained from each subject.

 » Results Top

Thirteen patients (two women and eleven men) fulfilling the ICHD-II criteria for episodic cluster headache (Cases 1-12) or chronic cluster headache (Case 13) were enrolled in this study. Mean age at onset of cluster headache was 34.7 years (range 25-52) and the mean age at initiation of topiramate treatment was 39 years (range 30-58). The mean duration of cluster headache period prior to topiramate treatment was 17.6 days (range 8-30 days) for the patients with episodic cluster headache and eight years for the patient with chronic cluster headache.

The clinical features and the response to treated with topiramate are summarized in [Table 1]. Of the 12 patients with episodic cluster headaches, nine patients experienced headache remission with topiramate therapy at a mean daily dosage of 273 mg (standard deviation (SD) ± 127, range 100-400). At the start of the study, of the nine patients with episodic headaches, eight patients rated their headaches as excruciating degree and the other one as severe. Topiramate significantly shortened the cluster period in these nine patients, and reduced the initial intensity of headache from excruciating to severe in a mean period of 4.3 days (SD 1.7, range 2-6), to moderate in 5.8 days (SD 2.6, range 2-10), and to mild in 7.4 days (SD 2.6, range 4-13). The mean period for remission was 10.7 days (SD 3.9, range 6-18), representing a reduction in the duration of 15% to 85% (median 51%) [Table 1]. Adverse effects were often mild to moderate but tolerable and included: paresthesia (84%), slow speech (54%), and dizziness (46%). Two patients discontinued the topiramate treatment due to adverse effects (Case 10 and 11), and one due to lack of efficacy (Case 12). After a remission period of more than two weeks, topiramate was gradually tapered. Case 9 had recurrence of headaches 16 days after completely discontinuing topiramate. The recurrent headaches remitted within three to four days after re-administration of topiramate in the previous dosage. The other eight patients had no relapse of cluster headache during a 3-month follow-up after withdrawal of topiramate therapy.

Case 13 was a 33-year-old woman, who suffered from attacks of stabbing pain in the periorbital region with ipsilateral lacrimation, nasal stuffiness, and conjunctiva injection for eight years, fulfilling the criteria for chronic cluster headache. She used to experience up to seven attacks a day, each lasting 60-120 minutes. Triptans and hyperbaric oxygen therapy were ineffective. High doses of steroid, verapamil (240 mg/day), lithium (900 mg/day) and other aggressive treatments including gabapentin (2400 mg/day), valproate (3000 mg/day), and imipramine (75 mg/day) had all failed to reduce the frequency of headaches. After topiramate treatment in a dosage of 400mg/day, there was rapid reduction in her headaches and had complete remission of headaches. Six months later, she discontinued the topiamate treatment, but had recurrence of headaches a week after the total withdrawal. However, the recurrent headaches remitted again within three to four days after re-administration of topiramate. Two years after topiramate therapy, she suffered from flank pain and renal stone of the right kidney was diagnosed.

 » Discussion Top

The present study suggests that topiramate is effective in the prevention of episodic and chronic cluster headache. Wheeler and Carrazana were the first to report remission of cluster headaches in nine of the ten patients within one to three weeks at a low dose of topiramate (50 to 125 mg/day). [4] In a recent open-label trial, of the 26 patients, 15 (58%) patients had headache remission within 1 to 28 days after topiramate treatment at doses ranging from 25 to 200 mg/day. [6] Another study reported no significant change in headache frequency with topiramate at 50 to 250 mg/day, with the daily number of attacks reduced by > 50% in just seven (21%) patients. [7] The effect of topiramate at low dosage in the prevention of cluster headache seems varied. Patients suffering from cluster headaches consistently report it as the most severe pain they have ever experienced. Immediate and optimal therapy is therefore urgently needed to alleviate headache intensity and prevent a cluster attack. Therefore, we decided to start with 50 mg twice daily of topiramate and rapidly titrate upwards depending on the tolerability. In the present study, we observed that 10 (77%) of 13 patients responded well to topiramate therapy and the cluster durations were reduced to approximately half of the previous usual cluster durations.

Chronic cluster headache accounts for 10-21% of all cluster headaches, [3],[10],[11] but is rare in the Taiwanese and Asians, [12] with Case 13 in the present series being the first case of chronic cluster headache ever reported in Taiwan. [13] Interestingly, she did not have a good response to topiramate treatment until the dose was reached 400 mg/day. In addition, when topiramate was withdrawn, her headache recurred within a few days. A similar observation has been reported in three patients with chronic cluster headache who had no response to topiramate 200 mg/day. [8] Though limited, these observations suggest that higher doses of topiramate may be beneficial to some patients with chronic cluster headache, who have no response at a low dose.

Oral bioavailability of topiramate is greater than 80%, and increases in the serum concentration are linearly dose-related at doses of 200-800 mg. [14] The incidence of adverse events may increase with an increasing dosage. Most adverse effects are related to the central nervous system. However, in studies relative to topiramate in partial epilepsy, most adverse effects of topiramate were not clearly dose-related, and there was no correlation between the topiramate dosage and the frequency of side effects leading to discontinuation across higher doses (200-1000 mg/day). [15],[16] In addition, the adverse-effect profile of topiramate in Taiwanese was different from that in whites. [15],[16],[17]

Topiramate is metabolized in the liver by the P450 microsome enzymes, such as CYP3A4. [18] The activity of the metabolic enzymes is mainly dependent on genetic, physiologic, and environmental effects. For instance, inter-ethnic and inter-individual difference in the distribution and frequency of metabolic enzyme variant alleles is often responsible for the development of a significant number of adverse drug reactions. [19],[20],[21],[22],[23] These genetic and environmental factors may explain why frequency of adverse effects is not related to the dose of topiramate, and the incidence is different between different populations. The incidence of adverse events was high, but tolerable in our patients. It seems our patients could endure higher dose of topiramate. Although slow titration is likely to alleviate occurrence of the adverse events, individual response may vary widely. Our study suggests that the tolerably rapid titration may be possible in certain patients with excruciating cluster headache for the additional benefits. Paresthesia was the first appearance of adverse effects, and occurred frequently in our patients, which is consistent with previous reports of topiramate therapy for cluster headache and migraine, [6],[24] but higher than that observed in patients with epilepsy who were treated with topiramate. [15],[16],[17] While the underlying mechanism remains unclear, it is possible that the activities of carbonic anhydrase are inhibited by rapid titration to high doses of topiramate [25] or this enzyme in the patients with cluster attack becomes more efficient to react with topiramate.

In conclusion, our study supports that topiramate is effective in the prevention of cluster headache. Since cluster headache is a very severe form of headache, our results suggest that a prompt dosage of topiramate upwards according to tolerability may be possible to offer immediate and additional benefits for both chronic and episodic cluster headache.

 » References Top

1.Leroux E, Ducros A. Cluster headache. Orphanet J Rare Dis 2008;3:20.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.The International Classification of Headache Disorders Cephalalgia. Cephalalgia 2004;24:S9-160.  Back to cited text no. 2      
3.Bahra A, May A, Goadsby PJ. Cluster headache: A prospective clinical study with diagnostic implications. Neurology 2002;58:354-61.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Wheeler SD, Carrazana EJ. Topiramate-treated cluster headache. Neurology 1999;13:234-6.  Back to cited text no. 4      
5.Forderreuther S, Mayer M, Straube A. Treatment of cluster headache with topiramate: Effects and side-effects in five patients. Cephalalgia 2002;22:186-9.  Back to cited text no. 5      
6.Lainez MJ, Pascual J, Pascual AM, Santonja JM, Ponz A, Salvador A. A Topiramate in the prophylactic treatment of cluster headache. Headache 2003;43:784-9.  Back to cited text no. 6      
7.Leone M, Dodick D, Rigamonti A, D'Amico D, Grazzi L, Mea E, et al. Topiramate in cluster headache prophylaxis: An open trial. Cephalalgia 2003;23:1001-2.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Mathew NT, Kailasam J, Meadors L. Prophylaxis of migraine, transformed migraine, and cluster headache with topiramate. Headache 2002;42:79-803.  Back to cited text no. 8      
9.Evans RW, Mathew NT. Handbook of headache. Philadelphia: Lippincott Williams and Wilkins: 2004.  Back to cited text no. 9      
10.Dodick DW, Rozen TD, Goadsby PJ, Silberstein SD. Cluster headache. Cephalalgia 2000;20:787-803.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Torelli P, Cologno D, Cademartiri C, Manzoni GC. Possible predictive factors in the evolution of episodic to chronic cluster headache. Headache 2000;40:798-808.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Lin KH, Wang PJ, Fuh JL, Lu SR, Chung CT, Tsou HK, et al. Cluster headache in the Taiwanese: A clinic-based study. Cephalalgia 2004;24:631-8.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Huang WY, Wu HM. Topiramate in the prevention of chronic cluster headache: A case report. Tuang Tien Med J 2006;1:39-43.  Back to cited text no. 13      
14.Bourgeois BF. Important pharmacokinetic properties of antiepileptic drugs. Epilepsia 1995;36:S1-7.  Back to cited text no. 14      
15.Privitera M, Fincham R, Penry J, Reife R, Kramer L, Pledger G, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Neurology 1996;46:1678-83.  Back to cited text no. 15  [PUBMED]    
16.Faught E, Wilder BJ, Ramsay RE, Reife RA, Kramer LD, Pledger GW, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Neurology 1996;46:1684-90.  Back to cited text no. 16  [PUBMED]    
17.Yen DJ, Yu HY, Guo YC, Chen C, Yiu CH, Su MS. A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy. Epilepsia 2000;41:1162-6.  Back to cited text no. 17  [PUBMED]    
18.Nallani SC, Glauser TA, Hariparsad N, Setchell K, Buckley DJ, Buckley AR, et al. Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia 2003;44:1521-8.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.Krishna DR, Shekar MS. Cytochrome P450 3A: Genetic polymorphisms and inter-ethnic differences. Methods Find Exp Clin Pharmacol 2005;27:559-67.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Hsieh KP, Lin YY, Cheng CL, Lai ML, Lin MS, Siest JP, et al. Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos 2001;29:268-73.   Back to cited text no. 20  [PUBMED]  [FULLTEXT]  
21.Du J, Xing Q, Xu L, Xu M, Shu A, Shi Y, et al. Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population. Pharmacogenomics 2006;7:831-41.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005;352:2211-21.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]  
23.Al Omari A, Murry DJ. Pharmacogenetics of the cytochrome P450 enzyme system: Review of current knowledge and clinical significance. J Pharm Prac 2007;20:206-18.  Back to cited text no. 23      
24.Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, et al. Topiramate for migraine prevention: A randomized controlled trial. JAMA 2004;291:965-73.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]  
25.Waugh J, Goa KL. Topiramate as monotherapy in newly diagnosed epilepsy. CNS Drugs 2003;17:985-92.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]  


  [Table 1]

This article has been cited by
1 Recent advances in the diagnosis and management of cluster headache
Emmanuelle A D Schindler, Mark J Burish
BMJ. 2022; : e059577
[Pubmed] | [DOI]
2 Cluster Headache Pathophysiology—A Disorder of Network Excitability?
Heiko Pohl, Peter S. Sandor, Lars Michels, Andreas R. Gantenbein
Clinical and Translational Neuroscience. 2021; 5(2): 16
[Pubmed] | [DOI]
3 Cluster headache pathophysiology — insights from current and emerging treatments
Diana Y. Wei, Peter J. Goadsby
Nature Reviews Neurology. 2021; 17(5): 308
[Pubmed] | [DOI]
4 Cluster headache: state of the art of pharmacological treatments and therapeutic perspectives
Pierre Courault, Geneviève Demarquay, Luc Zimmer, Sophie Lancelot
Fundamental & Clinical Pharmacology. 2021; 35(3): 595
[Pubmed] | [DOI]
5 Galcanezumab for the prevention of cluster headache
Luca Giani, Alberto Proietti Cecchini, Massimo Leone
Expert Opinion on Biological Therapy. 2020; 20(10): 1133
[Pubmed] | [DOI]
6 Chronic Cluster Headache Update and East–West Comparisons: Focusing on Clinical Features, Pathophysiology, and Management
Chia-Lin Tsai, Guan-Yu Lin, Sheng-Kai Wu, Fu-Chi Yang, Shuu-Jiun Wang
Current Pain and Headache Reports. 2020; 24(11)
[Pubmed] | [DOI]
7 Pharmacotherapy for Cluster Headache
Roemer B. Brandt, Patty G. G. Doesborg, Joost Haan, Michel D. Ferrari, Rolf Fronczek
CNS Drugs. 2020; 34(2): 171
[Pubmed] | [DOI]
8 Cluster headache
Arne May,Todd J. Schwedt,Delphine Magis,Patricia Pozo-Rosich,Stefan Evers,Shuu-Jiun Wang
Nature Reviews Disease Primers. 2018; 4: 18006
[Pubmed] | [DOI]
9 HPTLC Method for Estimation of Topiramate in Solubility Studies, Diffusion Studies, Plasma, Brain Homogenate and Pharmaceutical Formulation
Vijaykumar K. Parmar,Rajesh H. Parikh,Ravish J. Patel
Journal of Chromatographic Science. 2016; 54(7): 1105
[Pubmed] | [DOI]
10 Effect of topiramate on hippocampus-dependent spatial memory in rats
Boguslawa Pietrzak,Agnieszka Konopka,Jakub Wojcieszak
Pharmacological Reports. 2013; 65(5): 1152
[Pubmed] | [DOI]
11 Interdisciplinary management of headache disorders
Andrea L. Nicol,Nancy Hammond,Shamsha Velani Doran
Techniques in Regional Anesthesia and Pain Management. 2013; 17(4): 174
[Pubmed] | [DOI]
12 Cluster Headache
Charly Gaul, Hans-Christoph Diener, Oliver M. Müller
Deutsches Aerzteblatt Online. 2011;
[Pubmed] | [DOI]


Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow