Cluster headache primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sabeeh Islam, MBBS[2]


The drug of choice for primary prevention of cluster headache is Verapamil. Other agents that can be used also include glucocorticoids, topiramate and lithium.

Primary Prevention


  • Mostly used for episodic and chronic cluster headache.[1][2][3]
  • Usually starts with a dose of 240 mg and can be titrated upto 480 mg to 960 mg , depending upon the tolerance Dose is usually increased by 80mg every 10-14 days.[4][5]
  • An EKG is recommended before starting the treatment as Verapamil can cause EKG changes such as heart block and bradycardia, with a total daily dose of 480mg.
  • Side effects include: edema, gastrointestinal discomfort, constipation, dull headache, and gingival hyperplasia


  • Several open label studies have shown that glucocorticoids have reduced the frequency of cluster headaches[6][7]
  • Prednisone 30 mg daily or a higher dose can be used
  • Dexamethasone 8 mg daily in two divided doses


  • Topiramate is generally used as an add on therapy or combination therapy with Verapamil to prevent high dose use of verapamil and long term glucocorticoid therapy.[8][9]


  • Lithium is generally used for chronic cluster headaches when the first line agents are ineffective.[10][11]
  • There is very limited data about the efficacy and effectiveness of lithium.


  • Galcanezumab is generally used for prevention of episodic cluster headaches.[12]
  • Dose: 300 mg at the onset of cluster headache and later on once every month.

Greater occipital nerve blocks:

  • Refractory chronic cluster headaches sometimes respond temporarily to local glucocorticoid injection or greater occipital nerve block.[13][14][15][16][17]




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  2. Gabai IJ, Spierings EL (March 1989). "Prophylactic treatment of cluster headache with verapamil". Headache. 29 (3): 167–8. doi:10.1111/j.1526-4610.1989.hed2903167.x. PMID 2708046.
  3. Matharu MS, Boes CJ, Goadsby PJ (2003). "Management of trigeminal autonomic cephalgias and hemicrania continua". Drugs. 63 (16): 1637–77. doi:10.2165/00003495-200363160-00002. PMID 12904085.
  4. Cohen AS, Matharu MS, Goadsby PJ (August 2007). "Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy". Neurology. 69 (7): 668–75. doi:10.1212/01.wnl.0000267319.18123.d3. PMID 17698788.
  5. Lanteri-Minet M, Silhol F, Piano V, Donnet A (April 2011). "Cardiac safety in cluster headache patients using the very high dose of verapamil (≥720 mg/day)". J Headache Pain. 12 (2): 173–6. doi:10.1007/s10194-010-0289-x. PMC 3072493. PMID 21258839.
  6. Ekbom K, Hardebo JE (2002). "Cluster headache: aetiology, diagnosis and management". Drugs. 62 (1): 61–9. doi:10.2165/00003495-200262010-00003. PMID 11790156.
  7. Dodick DW, Capobianco DJ (February 2001). "Treatment and management of cluster headache". Curr Pain Headache Rep. 5 (1): 83–91. doi:10.1007/s11916-001-0015-0. PMID 11252143.
  8. Förderreuther S, Mayer M, Straube A (April 2002). "Treatment of cluster headache with topiramate: effects and side-effects in five patients". Cephalalgia. 22 (3): 186–9. doi:10.1046/j.1468-2982.2002.00339.x. PMID 12047455.
  9. Leone M, Dodick D, Rigamonti A, D'Amico D, Grazzi L, Mea E, Bussone G (December 2003). "Topiramate in cluster headache prophylaxis: an open trial". Cephalalgia. 23 (10): 1001–2. doi:10.1046/j.1468-2982.2003.00665.x. PMID 14984235.
  10. Steiner TJ, Hering R, Couturier EG, Davies PT, Whitmarsh TE (October 1997). "Double-blind placebo-controlled trial of lithium in episodic cluster headache". Cephalalgia. 17 (6): 673–5. doi:10.1046/j.1468-2982.1997.1706673.x. PMID 9350389.
  11. Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, Manzoni GC, Nappi G (June 1990). "Double blind comparison of lithium and verapamil in cluster headache prophylaxis". Headache. 30 (7): 411–7. doi:10.1111/j.1526-4610.1990.hed3007411.x. PMID 2205598.
  12. Goadsby PJ, Dodick DW, Leone M, Bardos JN, Oakes TM, Millen BA, Zhou C, Dowsett SA, Aurora SK, Ahn AH, Yang JY, Conley RR, Martinez JM (July 2019). "Trial of Galcanezumab in Prevention of Episodic Cluster Headache". N. Engl. J. Med. 381 (2): 132–141. doi:10.1056/NEJMoa1813440. PMID 31291515.
  13. Peres MF, Stiles MA, Siow HC, Rozen TD, Young WB, Silberstein SD (September 2002). "Greater occipital nerve blockade for cluster headache". Cephalalgia. 22 (7): 520–2. doi:10.1046/j.1468-2982.2002.00410.x. PMID 12230593.
  14. Leroux E, Valade D, Taifas I, Vicaut E, Chagnon M, Roos C, Ducros A (October 2011). "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. 10 (10): 891–7. doi:10.1016/S1474-4422(11)70186-7. PMID 21903477.
  15. Ambrosini A, Vandenheede M, Rossi P, Aloj F, Sauli E, Pierelli F, Schoenen J (November 2005). "Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study". Pain. 118 (1–2): 92–6. doi:10.1016/j.pain.2005.07.015. PMID 16202532.
  16. Gantenbein AR, Lutz NJ, Riederer F, Sándor PS (June 2012). "Efficacy and safety of 121 injections of the greater occipital nerve in episodic and chronic cluster headache". Cephalalgia. 32 (8): 630–4. doi:10.1177/0333102412443335. PMID 22623755.
  17. Lambru G, Abu Bakar N, Stahlhut L, McCulloch S, Miller S, Shanahan P, Matharu MS (February 2014). "Greater occipital nerve blocks in chronic cluster headache: a prospective open-label study". Eur. J. Neurol. 21 (2): 338–43. doi:10.1111/ene.12321. PMID 24313966.
  18. Matharu M (February 2010). "Cluster headache". BMJ Clin Evid. 2010. PMC 2907610. PMID 21718584.
  19. Hering R, Kuritzky A (September 1989). "Sodium valproate in the treatment of cluster headache: an open clinical trial". Cephalalgia. 9 (3): 195–8. doi:10.1046/j.1468-2982.1989.0903195.x. PMID 2507161.
  20. Sicuteri F, Fusco BM, Marabini S, Campagnolo V, Maggi CA, Geppetti P, Fanciullacci M (1989). "Beneficial effect of capsaicin application to the nasal mucosa in cluster headache". Clin J Pain. 5 (1): 49–53. doi:10.1097/00002508-198903000-00010. PMID 2520386.
  21. Fusco BM, Marabini S, Maggi CA, Fiore G, Geppetti P (December 1994). "Preventative effect of repeated nasal applications of capsaicin in cluster headache". Pain. 59 (3): 321–5. doi:10.1016/0304-3959(94)90017-5. PMID 7708405.
  22. Loder E (January 2002). "Naratriptan in the prophylaxis of cluster headache". Headache. 42 (1): 56–7. doi:10.1046/j.1526-4610.2002.02014.x. PMID 12005276.
  23. Mulder LJ, Spierings EL (December 2002). "Naratriptan in the preventive treatment of cluster headache". Cephalalgia. 22 (10): 815–7. doi:10.1046/j.1468-2982.2002.00424.x. PMID 12485208.
  24. Dodick DW, Rozen TD, Goadsby PJ, Silberstein SD (November 2000). "Cluster headache". Cephalalgia. 20 (9): 787–803. doi:10.1046/j.1468-2982.2000.00118.x. PMID 11167909.
  25. Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G (November 1996). "Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups". Cephalalgia. 16 (7): 494–6. doi:10.1046/j.1468-2982.1996.1607494.x. PMID 8933994.
  26. Pringsheim T, Magnoux E, Dobson CF, Hamel E, Aubé M (September 2002). "Melatonin as adjunctive therapy in the prophylaxis of cluster headache: a pilot study". Headache. 42 (8): 787–92. doi:10.1046/j.1526-4610.2002.02181.x. PMID 12390642.
  27. Antonaci F, Costa A, Ghirmai S, Sances G, Sjaastad O, Nappi G (April 2003). "Parenteral indomethacin (the INDOTEST) in cluster headache". Cephalalgia. 23 (3): 193–6. doi:10.1046/j.1468-2982.2003.00495.x. PMID 12662186.
  28. Prakash S, Shah ND, Chavda BV (August 2010). "Cluster headache responsive to indomethacin: Case reports and a critical review of the literature". Cephalalgia. 30 (8): 975–82. doi:10.1177/0333102409357642. PMID 20656709.

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