Prophylactic Treatment With Atorvastatin for Episodic Migraine.

Summary

The main objective of this study is to see whether the favorable preventative effect of Atorvastatin 40mg per day in episodic migraine, that was found previously in three smaller randomized controlled cross-over studies, can be confirmed in a larger, multicenter, randomized controlled parallel group study. In addition it will be investigated whether 1) there is an effect of a daily dose of 20mg Atorvastatin, 2) whether the favorable side effect profile, seen in previous studies, can be confirmed, and whether it is even better with the smaller dose, and 3) estimating the cost of Atorvastatin treatment, considering cost of medicine, cost of acute attack medicine, and cost of lost worktime.

Timeline

Start

2024-05-01

Primary completion

2028-12-31

Completion

2029-02-28

Publications

• Background Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z; Lifting The Burden: the Global Campaign against Headache. Migraine remains second among the world's causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020 Dec 2;21(1):137. doi: 10.1186/s10194-020-01208-0. No abstract available.
• Background Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022 Apr 12;23(1):34. doi: 10.1186/s10194-022-01402-2.
• Background Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sandor PS; European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009 Sep;16(9):968-81. doi: 10.1111/j.1468-1331.2009.02748.x.
• Background Langohr HD, Gerber WD, Koletzki E, Mayer K, Schroth G. Clomipramine and metoprolol in migraine prophylaxis--a double-blind crossover study. Headache. 1985 Mar;25(2):107-13. doi: 10.1111/j.1526-4610.1985.hed2502107.x. No abstract available.
• Background Ziegler DK, Hurwitz A, Hassanein RS, Kodanaz HA, Preskorn SH, Mason J. Migraine prophylaxis. A comparison of propranolol and amitriptyline. Arch Neurol. 1987 May;44(5):486-9. doi: 10.1001/archneur.1987.00520170016015.
• Background Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003 Jan 1;289(1):65-9. doi: 10.1001/jama.289.1.65.
• Background Stovner LJ, Linde M, Gravdahl GB, Tronvik E, Aamodt AH, Sand T, Hagen K. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2014 Jun;34(7):523-32. doi: 10.1177/0333102413515348. Epub 2013 Dec 11.
• Background Mei D, Capuano A, Vollono C, Evangelista M, Ferraro D, Tonali P, Di Trapani G. Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study. Neurol Sci. 2004 Dec;25(5):245-50. doi: 10.1007/s10072-004-0350-0.
• Background Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D; MIGR-002 Study Group. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004 Feb 25;291(8):965-73. doi: 10.1001/jama.291.8.965.
• Background Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B. Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Clin Neurol Neurosurg. 2004 Dec;107(1):44-8. doi: 10.1016/j.clineuro.2004.03.004.
• Background Couch JR; Amitriptyline Versus Placebo Study Group. Amitriptyline in the prophylactic treatment of migraine and chronic daily headache. Headache. 2011 Jan;51(1):33-51. doi: 10.1111/j.1526-4610.2010.01800.x. Epub 2010 Nov 10.
• Background Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, Martelletti P. Correction to: European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 2019 May 23;20(1):58. doi: 10.1186/s10194-019-0972-5.
• Background Katsarava Z, Mania M, Lampl C, Herberhold J, Steiner TJ. Poor medical care for people with migraine in Europe - evidence from the Eurolight study. J Headache Pain. 2018 Feb 1;19(1):10. doi: 10.1186/s10194-018-0839-1.
• Background Buettner C, Nir RR, Bertisch SM, Bernstein C, Schain A, Mittleman MA, Burstein R. Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Ann Neurol. 2015 Dec;78(6):970-81. doi: 10.1002/ana.24534. Epub 2015 Nov 13.
• Background Hesami O, Sistanizad M, Asadollahzade E, Johari MS, Beladi-Moghadam N, Mazhabdar-Ghashghai H. Comparing the Effects of Atorvastatin With Sodium Valproate (Divalproex) on Frequency and Intensity of Frequent Migraine Headaches: A Double-blind Randomized Controlled Study. Clin Neuropharmacol. 2018 May/Jun;41(3):94-97. doi: 10.1097/WNF.0000000000000280.
• Background Ganji R, Majdinasab N, Hesam S, Rostami N, Sayyah M, Sahebnasagh A. Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial. J Pharm Health Care Sci. 2021 Apr 1;7(1):12. doi: 10.1186/s40780-021-00198-8.
• Background Sherafat A, Sahebnasagh A, Rahmany R, Mohammadi F, Saghafi F. The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial. Neurol Res. 2022 Apr;44(4):311-317. doi: 10.1080/01616412.2021.1981105. Epub 2022 Jan 17.
• Background Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res. 1992 Nov;33(11):1569-82. No abstract available.
• Background Musial J, Undas A, Gajewski P, Jankowski M, Sydor W, Szczeklik A. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int J Cardiol. 2001 Feb;77(2-3):247-53. doi: 10.1016/s0167-5273(00)00439-3.
• Background Yanuck D, Mihos CG, Santana O. Mechanisms and clinical evidence of the pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in central nervous system disorders: a comprehensive review. Int J Neurosci. 2012 Nov;122(11):619-29. doi: 10.3109/00207454.2012.704455. Epub 2012 Aug 14.
• Background Zhou Q, Liao JK. Pleiotropic effects of statins. - Basic research and clinical perspectives -. Circ J. 2010 May;74(5):818-26. doi: 10.1253/circj.cj-10-0110. Epub 2010 Apr 15.
• Background Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials. J Affect Disord. 2016 Aug;200:235-42. doi: 10.1016/j.jad.2016.04.047. Epub 2016 Apr 27.
• Background Millar PJ, Floras JS. Statins and the autonomic nervous system. Clin Sci (Lond). 2014 Mar;126(6):401-15. doi: 10.1042/CS20130332.
• Background Lennernas H. Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. doi: 10.2165/00003088-200342130-00005.
• Background Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. doi: 10.1016/s0002-9149(03)00530-7.
• Background Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Houle TT, Hoek TCVD, Martinelli D, Terwindt GM; International Headache Society Clinical Trials Committee. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults. Cephalalgia. 2020 Sep;40(10):1026-1044. doi: 10.1177/0333102420941839. Epub 2020 Jul 28.
• Background Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
• Background Bhatt A. Protocol deviation and violation. Perspect Clin Res. 2012 Jul;3(3):117. doi: 10.4103/2229-3485.100663. No abstract available.
• Background Buettner C, Burstein R. Association of statin use and risk for severe headache or migraine by serum vitamin D status: a cross-sectional population-based study. Cephalalgia. 2015 Aug;35(9):757-66. doi: 10.1177/0333102414559733. Epub 2014 Nov 25.
• Background Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. 2014 Apr;21(4):464-74. doi: 10.1177/2047487314525531. Epub 2014 Mar 12.
• Background Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P; ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017 Jun 24;389(10088):2473-2481. doi: 10.1016/S0140-6736(17)31075-9. Epub 2017 May 2.
• Background Jenssen AB, Stovner LJ, Tronvik E, Sand T, Helde G, Gravdahl GB, Hagen K. The crossover design for migraine preventives: an analyses of four randomized placebo-controlled trials. J Headache Pain. 2019 Dec 27;20(1):119. doi: 10.1186/s10194-019-1067-z.

Drugs

Indications