BTG - New Treatment Strategies for Migraine Prevention

BTG - New Treatment Strategies for Migraine Prevention

Alan Rapoport, Christina Sun
Published: US Neurological Disease report 2006 - In association with BTG
download article

| More
dots

Migraine is a common neurological disorder that affects 18% of women and 6% of men in the US.1 Those migraineurs who suffer frequent headaches that interfere with routine activities generally require treatment with a daily preventive agent in addition to abortive drugs. Beta-blockers, calcium-channel blockers, antidepressants, and anti-epileptics comprise the major drug groups used in migraine prevention. Currently, however, only four drugs are approved for use as migraine preventive agents in the US—timolol, propranolol, divalproex sodium, and topiramate. In recent years, many other medications and supplements have emerged as effective, tolerable options for migraine prevention. The aim of this article is to provide an overview of the newer, less frequently prescribed agents for migraine prevention. The reader should bear in mind that some of them still require further investigation with larger, double-blind, placebocontrolled studies.

Triptans
The triptans—sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan and eletriptan— revolutionized the acute treatment of migraine when they became available over a decade ago. They are used at headache onset, and are available in several forms. All are available as tablets, while two— zolmitriptan and rizatriptan—are also available in orally dissolvable tablets. Sumatriptan has an injectable form, and sumatriptan and zolmitriptan are available as nasal sprays.

Though these drugs have been traditionally used as acute migraine medications, recent studies have suggested that the triptans can be used in the preventive treatment of headaches refractory to conventional first-line therapies. Rapoport et al.2 initially published a retrospective review of patients with transformed migraine using naratriptan preventively for extended periods of time, and found that there was a statistically significant reduction in the frequency of headache days at two months, six months, and one year after treatment was initiated. Some of these patients have remained on daily naratriptan for seven years without adverse events. Since the retrospective nature of the study limited the generalization of those results, Sheftell et al.3 conducted a prospective study assessing the efficacy, safety, and tolerability of naratriptan in the prevention of transformed migraine in patients refractory to traditional therapies. The intent-to-treat population comprised 30 subjects, who received naratriptan 2.5mg twice-daily for three months.A significant reduction in headache frequency was obtained at one, two, and three months. No serious adverse events were reported, and no significant changes were observed in blood pressure, heart rate, electrocardiograms or ophthalmologic exams.

Anti-epileptics

Topiramate
In recent years, topiramate, an anti-epileptic drug, has emerged as an effective choice for migraine prevention, and in 2004 it was approved by the US Food and Drug Administration (FDA) for that use.The exact mechanism by which topiramate works to prevent migraine is unknown. However, it is known to have multiple mechanisms of action, several of which may be involved in decreasing migraine frequency. Topiramate enhances the inhibitory effects of gamma-aminobutyric acid, blocks the excitatory effect of glutamate, blocks sodium channels, limiting repetitive firing, reduces calcium channel activity, and inhibits carbonic anhydrase.4,5

The efficacy of topiramate in migraine prevention has been shown in more patients in controlled trials than any other migraine preventive agent. Following a number of open-label and small controlled studies 6–9, several large, double-blind, placebo-controlled trials established that topiramate is effective as migraine preventive therapy. The recommended daily dose of topiramate for migraine prevention is 100mg, in two divided doses. Titration to target dose involves initiating the drug at 25mg at night and increasing by 25mg weekly until the target dose of 50mg twice daily, or the maximum-tolerated dose, is reached. At recommended doses, topiramate is generally well tolerated, although several potential adverse events must be discussed with the patient, such as cognitive dysfunction, paresthesias and weight loss.4,10,11

Levetiracetam
Levetiracetam (LEV) is an anti-epileptic drug whose mechanism of action is not fully understood. Its efficacy in migraine prevention may be related to a possible effect on cortical spreading depression, which is an early pathophysiological process in a migraine attack.12 Open-label trials have demonstrated the efficacy of LEV in the prevention of refractory migraine.13,14 A recent study by Rapoport et al.15 found a significant reduction in monthly headache frequency in patients on daily LEV after one, two, and three months. The minimally effective dose appears to be 1,500mg, and most patients need 2,000–2,500mg daily. No serious adverse events were reported.

123next ›last »
References:
  1. Lipton R B, Stewart W F, Diamond S et al., Prevalence and burden of migraine in the United States: data from the American Migraine Study II , Headache (2001);41: pp. 646 657.
  2. Rapoport A M, Bigal M E,Volcy M et al., Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases , Headache (2003);43: pp. 482 489.
  3. Sheftell F D, Rapoport A M,Tepper S J, Bigal M E, Naratriptan in the preventive treatment of refractory transformed migraine: a prospective pilot study , Headache (2005);45: pp.1,400 1,406.
  4. Silberstein S D, Neto W, Schmitt J, Jacobs D for the MIGR-001 Study Group, Topiramate in migraine prevention: results of a large, controlled trial , Arch Neurol (2004);61: pp. 490 495.
  5. Shank R P, Gardocki J F, Streeter A J, Maryanoff B E, An overview of the preclinical aspects of TPM: pharmacology, pharmacokinetics, and mechanism of action , Epilepsia (2000);41: pp. S3 S9.
  6. Shuaib A,Ahmed F, Muratoglu M, Kochanski P, Topiramate in migraine prophylaxis; a pilot study , Cephalalgia (1999);19: pp. 379 380 (abstract).
  7. Edward K R, Glantz M J, Shea P et al., A double-blind, randomized trial of topiramate versus placebo in the prophylactic treatment of migraine headache with and without aura, Cephalalgia (2000);20: p. 316.
  8. Potter D L, Hart D E, Calder C S, Storey J R, A double-blind, randomized, placebo-controlled, parallel study to determine the efficacy of topiramate in the prophylactic treatment of migraine , Neurology (2000);54: p. A15 (abstract).
  9. Storey J R, Calder C S, Hart D E, Potter D L, Topiramate in migraine prevention: a double-blind, placebo-controlled study , Headache (2001);41: pp. 968 975.
  10. Brandes J L, Saper J P, Diamond M et al., Topiramate for migraine prevention: a randomized controlled trial , JAMA (2004); 291: pp. 965 973.
  11. Diener H C,Tfelt-Hansen P, Dahlof C et al., for 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: pp. 943 950.
  12. Rapoport A M, Bigal M E, Migraine preventive therapy: current and emerging treatment options , Neurol Sci (2005);26: pp. S111 S120.
  13. Krusz J C, Levetiracetam as prophylaxis for resistant headaches , Cephalalgia (2001);21: p.373 (Abstract).
  14. Drake M E, Greathouse N I,Armentbright A D, Renner J B, Levetiracetam for preventive treatment of migraine , Cephalalgia (2001);21: p.373 (abstract).
  15. Rapoport A M, Sheftell F D, Tepper S J, Bigal M E, Levetiracetam for preventive treatment of transformed migraine , Headache (in press).
  16. Kruscz J C, Zonisamide in the treatment of headache disorders , Cephalalgia (2001);21: p. 374 (abstract).
  17. Drake M E, Greathouse N I, Armentbright A D et al., Preventive treatment of migraine with zonisamide , Cephalalgia (2001);21: p. 374 (abstract).
  18. Shneker B F,McAuley J W, Pregabalin: a new neruomodulator with broad therapeutic indications , Ann Pharmacother (2005); 39: pp. 2,029 2,037.
  19. Chronicle E, Mulleners W, Anticonvulsant drugs for migraine prophylaxis , Cochrane Database Syst Rev (2004);3: CD 003226.
  20. Mathew N T, Rapoport A, Saper J et al., Efficacy of gabapentin in migraine prophylaxis , Headache (2001);41: pp. 119 128.
  21. Tronvik E, Stovner L J, Helde G et al., Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial , JAMA (2003);289: pp. 65 69.
  22. Grossman M, Schmidrams H, An extract of Petasites hybridus is effective in the prophylaxis of migraine , Int J Clin Pharmacol Ther (2000);38: pp. 430 435.
  23. Eaton J, Butterbur, herbal help for migraine , Natural Pharmacy (1998);2: pp. 23 24.
  24. Sheftell F, Rapoport A,Weeks R et al., Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers , Headache (2000);40: pp. 158 164.
  25. Lipton R B, Gobel H, Einhaupl K M, Wilks K, Mauskop A, Petasites hybridus root (butterbur) is an effective preventive treatment for migraine , Neurology (2004);63: pp. 2,240 2,244.
  26. Welch K M A, Ramadan N M, Mitochondria, magnesium and migraine , J Neurol Sci (1995);134: pp. 9 14.
  27. Jain A A C, Sethi N C, Balbar P K, A clinical electroencephalographic and trace element study with special reference to zinc, copper and magnesium I serum and cerebrospinal fluid in cases of migraine , J Neurol Suppl (1985);232: p. 161.
  28. Schoenen J, Sianard-Gainko J, Lenaerts M, Blood magnesium levels in migraine , Cephalalgia (1991);111: pp. 97 99.
  29. Sarchielli P, Coata G, Firenze C et al., Serum and salivary magnesium levels in migraine and tension type headache: results in a group of adult patients , Cephalalgia (1992);12: pp. 21 27.
  30. Ramadan N M, Halvorson H,Vande-Linde A, Low brain magnesium in migraine , Headache (1989);29: pp. 590 593.
  31. Peikert A,Wilimzig C, Kone-Voland R, Prophylaxis of migraine with oral magnesium: results from a prospective, multicenter, placebo-controlled and double-blind randomized study , Cephalalgia (1996);16: pp. 257 263.
  32. Pfaffenrath V, Ostreich W, Haase W, Magnesium in the prophylaxis of migraine a double-blind, placebo-controlled study , Cephalalgia (1996);16: pp. 436 440.
  33. Facchinetti F, Sances G, Borella P et al., Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium , Headache (1991);31: pp. 298 230.
  34. Mauskop A,Altura B T, Cracco R Q,Altura B M, Deficiency in serum ionized magnesium but not total magnesium in patients with migraines. Possible role of ICa2+/Mg2+ ratio , Headache (1993);33: pp. 135 138.
  35. Bigal M, Rapoport A M, Sheftell F, Tepper S J, New migraine preventive options: an update with pathophysiological considerations , Rev Hosp Clin Fac Med Sao Paulo (2002);57: pp. 293 298.
  36. Bresolin N, Martinelli P, Barbiroli B et al., Muscle mitochondrial deletion and 31P NMR spectroscopy alterations in migraine patients , J Neurol Sci (1991);104: pp. 182 189.
  37. Montagna P, Cortelli P, Barbiroli B, Magnetic resonance spectroscopy studies in migraine , Cephalalgia (1994);14: pp. 184 193.
  38. Rozen T D, Oshinsky M L, Gebeline C A et al., Open label trial of coenzyme Q10 as a migraine preventive , Cephalalgia (2002);22: pp. 137 141.
  39. Sandor P S, DiClemente L, Coppola G et al., Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial , Neurology (2005);64: pp. 713 715.
  40. Binder W J, Brin M F, Blitzer A et al., Botulinum toxin type A (BOTOX®) for treatment of migraine headaches: an open-label study , Otolaryngol Head Neck Surg (2000);123: pp. 669 676.
  41. Zwart J A, Bovim G, Sand T, Sjaastad O, Tension headache: botulinum toxin paralysis of temporal muscles , Headache (1994);34: pp. 458 462.
  42. Relja M A, Treatment of tension-type headache by local injection of botulinum toxin , Eur J Neurol (1997);4 (Suppl 2): pp. 71 72.
  43. Silberstein S D, Mathew N, Saper J, Jenkins S, Migraine clinical research group: botulinum toxin type A as a migraine preventive treatment , Headache (2000);40: pp. 445 450.
  44. Tepper S J, Bigal M E, Sheftell F D, Rapoport A M, Botulinum neurotoxin type A in the preventive treatment of refractory headache: a review of 100 consecutive cases , Headache (2004);44: pp. 794 800.
  45. Blumenfeld A M, Binder W, Silberstein S D, Blitzer A, Procedures for administering botulinum toxin type A for migraine and tension-type headache , Headache (2003);43: pp. 884 891.
  46. Sheftell F D, Rapoport A M,Walker B et al., Leukotriene antagonists in the prophylaxis of migraine: a potential role for a new class of agents , Headache (1999);39: p. 381.

Copyright® 2012 Touch Group PLC. All rights reserved.
Touch Neurology is for informational purposes and should not be considered medical advice, diagnosis or treatment recommendations.