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J Headache Pain. 2008 February; 9(1): 37–41.
Published online 2008 January 23. doi:  10.1007/s10194-008-0002-5
PMCID: PMC3476175

The effect of sodium valproate on chronic daily headache and its subgroups


The objective of the study was to assess the efficacy and tolerability of sodium valproate (VPA) on chronic daily headache (CDH) in a prospective, double-blind, randomized, placebo-controlled trial. Seventy patients were included in the study. Twenty-nine had chronic migraine (CM) and 41 had chronic tension-type headache (CTTH). VPA and placebo were applied for 3 months to 40 and 30 patients, respectively. Visual analog scale (VAS) and pain frequency (PF) were used for evaluation. VPA decreased the maximum pain VAS levels (MaxVAS) and PF at the end of the study (P = 0.028 and P = 0.000, respectively), but did not change general pain VAS (GnVAS) levels (P = 0.198). In CM patients, the decreases in MaxVAS, GnVAS and PF parameters were more in VPA treated patients (P = 0.006, P = 0.03, and P = 0.000, respectively). VPA treatment caused more reduction in PF than placebo in the CTTH subgroup (P = 0.000). VPA is effective in the prophylactic treatment of CDH by reducing MaxVAS levels and PF. It was more effective in CM than in CTTH.

Keywords: Chronic daily headache, Chronic migraine, Chronic tension type headache, Sodium valproate

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Selected References

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1. Schwartz TH, Karpitskiy VV, Sohn RS. Intravenous valproate sodium in the treatment of daily headache. Headache. 2002;42(6):519–522. doi: 10.1046/j.1526-4610.2002.02127.x. [PubMed] [Cross Ref]
2. Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headache: a field study of revised IHS criteria. Neurology. 1996;47:871–875. [PubMed]
3. Freitag FG, Diamond S, Diamond ML, Urban GJ. Divalproex in the long-term treatment of chronic daily headache. Headache. 2001;41:271–278. doi: 10.1046/j.1526-4610.2001.111006271.x. [PubMed] [Cross Ref]
4. Sorensen KV. Valproate: a new drug in migraine prophylaxis. Acta Neurol Scand. 1988;78:346–348. doi: 10.1111/j.1600-0404.1988.tb03667.x. [PubMed] [Cross Ref]
5. Hering R, Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia. 1992;12(2):81–84. doi: 10.1046/j.1468-2982.1992.1202081.x. [PubMed] [Cross Ref]
6. Hering R, Kuritzky A. Sodium valproate in the treatment of cluster headache: an open clinical trial. Cephalalgia. 1989;9:195–198. doi: 10.1046/j.1468-2982.1989.0903195.x. [PubMed] [Cross Ref]
7. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study. Neurology. 1994;44(4):647–651. [PubMed]
8. Freitag FG, Collins SD, Carlson HA, Goldstein J, Saper J, Silberstein S, Mathew N, Winner PK, Deaton R, Sommerville Depakote K; ER, Migraine Study Group A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;11(58):1652–1659. [PubMed]
9. Taylor K, Goldstein J. High-dose versus low-dose valproic acid as a prophylactic medication. Headache. 1996;36(8):514–515. doi: 10.1046/j.1526-4610.1996.3608514.x. [PubMed] [Cross Ref]
10. Klapper J. Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia. 1997;17:103–108. doi: 10.1046/j.1468-2982.1997.1702103.x. [PubMed] [Cross Ref]
11. Hering R, Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia. 1992;12:81–84. doi: 10.1046/j.1468-2982.1992.1202081.x. [PubMed] [Cross Ref]
12. Kaniecki RG. A comparison of divalproex with propanolol and placebo for the prophylaxis of migraine without aura. Arch Neurol. 1997;54:1141–1145. [PubMed]
13. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo controlled crossover study. Neurology. 1994;44:647–651. [PubMed]
14. Silberstein SD, Neto W, Schmitt J, Jacobs D, MIGR-001 Study Group Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–495. doi: 10.1001/archneur.61.4.490. [PubMed] [Cross Ref]
15. Brandes JL, Saper JR, Diamond M, et al MIGR-002 Study Group (2004) Topiramate for migraine prevention: a randomized controlled trial. JAMA 291:965–973 [PubMed]
16. Diener HC, Tfelt-Hansen P, Dahlof C, Lainez MJ, Sandrini G, Wang SJ, Neto W, Vijapurkar U, Doyle A, Jacobs D, The MIGR-003 Study Group Topiramate in migraine prophylaxis: results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943–950. doi: 10.1007/s00415-004-0464-6. [PubMed] [Cross Ref]
17. Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41:119–128. doi: 10.1046/j.1526-4610.2001.111006119.x. [PubMed] [Cross Ref]
18. Pascual J, Lainez MJ, Dodick D, Hering-Hanit R. Antiepileptic drugs for the treatment of chronic and episodic cluster headache. Headache. 2007;47(1):81–89. doi: 10.1111/j.1526-4610.2007.00653.x. [PubMed] [Cross Ref]
19. Mathew NT. The prophylactic treatment of chronic daily headache. Headache. 2006;46(10):1552–1564. doi: 10.1111/j.1526-4610.2006.00621.x. [PubMed] [Cross Ref]
20. Silberstein SD. Chronic daily headache. JAOA. 2005;105(4 Suppl 2):23S–29S. [PubMed]
21. Mathew NT, Ali S. Valproate in the treatment of persistent chronic daily headache. An open label study. Headache. 1991;31(2):71–74. doi: 10.1111/j.1526-4610.1991.hed3102071.x. [PubMed] [Cross Ref]
22. Rothrock JF. Management of chronic daily headache utilizing a uniform treatment pathway. Headache. 1999;39:650–653. doi: 10.1046/j.1526-4610.1999.3909650.x. [PubMed] [Cross Ref]
23. Vijayan N, Spillane T. Valproic acid treatment of chronic daily headache. Headache. 1995;35:540–543. doi: 10.1111/j.1526-4610.1995.hed3509540.x. [PubMed] [Cross Ref]
24. Lenaerts M, Bastings E, Sianard J, Schoenen J. Sodium valproate in severe migraine and tension-type headache: an open study of long-term efficacy and correlation with blood levels. Acta Neurol Belg. 1996;96(2):126–129. [PubMed]
25. Rothrock JF, Mendizabal JE. An analysis of the “carry-over effect” following successful short-term treatment of transformed migraine with divalproex sodium. Headache. 2000;40(1):17–19. doi: 10.1046/j.1526-4610.2000.00002.x. [PubMed] [Cross Ref]

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