Skip to main content
SpringerLink
Log in

Tanacetum parthenium and Salix alba (Mig-RL®) Combination in Migraine Prophylaxis

A Prospective, Open-Label Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background: Tanacetum parthenium (feverfew) has been used traditionally to treat migraine, and although its mechanism of action is not fully understood, serotonin 5-HT receptor blocking effects have been suggested. T. parthenium and Salix alba (white willow) either alone or in combination (Mig-RL®) were recently shown to inhibit binding to 5-HT2A/2C receptors; T. parthenium failed to recognise 5-HT1D receptors, whereas S. alba or the combination did. It was hypothesised that S. alba in combination with T. parthenium may provide superior migraine prophylactic activity compared with T. parthenium alone.

Methods: A prospective, open-label study was performed in 12 patients diagnosed with migraine without aura. Twelve weeks’ treatment with T. parthenium 300mg plus S. alba 300mg (Mig-RL®) twice daily was administered to determine the effects of therapy on migraine attack frequency (primary efficacy criterion), intensity and duration (secondary efficacy criteria), and quality of life, together with tolerability for patients.

Results: Attack frequency was reduced by 57.2% at 6 weeks (p < 0.029) and by 61.7% at 12 weeks (p < 0.025) in nine of ten patients, with 70% patients having a reduction of at least 50%. Attack intensity was reduced by 38.7% at 6 weeks (p < 0.005) and by 62.6% at 12 weeks (p < 0.004) in ten of ten patients, with 70% of patients having a reduction of at least 50%. Attack duration decreased by 67.2% at 6 weeks (p < 0.001) and by 76.2% at 12 weeks (p < 0.001) in ten of ten patients. Two patients were excluded for reasons unrelated to treatment. Self-assessed general health, physical performance, memory and anxiety also improved by the end of the study. Mig-RL® treatment was well tolerated and no adverse events occurred.

Conclusion: The remarkable efficacy of Mig-RL® in not only reducing the frequency of migraine attacks but also their pain intensity and duration in this trial warrants further investigation of this therapy in a double-blind, randomised, placebo-controlled investigation involving a larger patient population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2
Fig. 3
Table II
Table III

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Silberstein SD, Lipton RB, Dalessio DJ. Overview, diagnosis and classification of headache. In: Silberstein SD, Lipton RB, Dalessio DJ, editors. Wolff’s headache and other head pain. 7th ed. New York: Oxford University Press, 2001: 6–26

    Google Scholar 

  2. Goadsby PJ, Lipton RB, Ferrari MD. Migraine—current understanding and treatment. N Engl J Med 2002; 346(4): 257–70

    Article  PubMed  CAS  Google Scholar 

  3. Lipton RB, Diamond S, Reed M, et al. Migraine diagnosis and treatment: results from the American Migraine Study: II. Headache 2001; 41(7): 638–45

    Article  PubMed  CAS  Google Scholar 

  4. Ferrari MD, Goadsby PJ, Roon KI, et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002; 22(8): 633–58

    Article  PubMed  CAS  Google Scholar 

  5. Massiou H, Bousser MG. Prophylactic drug treatment of migraine. Rev Neurol (Paris) 2005; 161(6–7): 681–4

    Article  CAS  Google Scholar 

  6. Diener HC, Limmroth V. Advances in pharmacological treatment of migraine. Expert Opin Investig Drugs 2001; 10(10): 1831–45

    Article  PubMed  CAS  Google Scholar 

  7. Pietrobon D, Striessnig J. Neurobiology of migraine. Nat Rev Neurosci 2003; 4(5): 386–98

    Article  PubMed  CAS  Google Scholar 

  8. Waeber C, Moskowitz MA. Therapeutic implications of central and peripheral neurologic mechanisms in migraine. Neurology 2003; 61(8 Suppl. 4): S9–S20

    Article  PubMed  Google Scholar 

  9. Goadsby PJ. Can we develop neurally acting drugs for the treatment of migraine? Nat Rev Drug Discov 2005; 4(9): 741–50

    Article  PubMed  CAS  Google Scholar 

  10. Welch KM. Contemporary concepts of migraine pathogenesis. Neurology 2003; 61(8 Suppl. 4): S2–8

    Article  PubMed  CAS  Google Scholar 

  11. Welch KM. Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention. Headache 2005; 45Suppl. 1: S25–32

    Article  PubMed  Google Scholar 

  12. Humphrey PP, Feniuk W, Perren MJ, et al. Serotonin and migraine. Ann N Y Acad Sci 1990; 600: 587–600

    Article  PubMed  CAS  Google Scholar 

  13. Humphrey PP. 5-Hydroxytryptamine and the pathophysiology of migraine. J Neurol 1991; 238Suppl. 1: S38–44

    Article  PubMed  Google Scholar 

  14. Lance JW. 5-Hydroxytryptamine and its role in migraine. Eur Neurol 1991; 31(5): 279–81

    Article  PubMed  CAS  Google Scholar 

  15. Sicuteri F, Testi A, Anselmi B. Biochemical investigations in headache: increase in the hydroxyindoleacetic acid excretion during migraine attacks. Int Arch Allerg 1961; 19: 55–8

    Article  CAS  Google Scholar 

  16. Hamel E, Saxena PR. 5-Hydroxytryptamine involvement in migraines. In: Olesen J, Tfelt-Hansen P, Welch KMA, et al., editors. The headaches. Chap. 29. 3rd ed. Pennsylvania: Lippincott Williams & Wilkins, 2006: 275–280

    Google Scholar 

  17. Feniuk W, Humphrey PP, Perren MJ, et al. Rationale for the use of 5-HT1-like agonists in the treatment of migraine. J Neurol 1991; 238Suppl. 1: S57–61

    Article  PubMed  Google Scholar 

  18. John GW, Goadsby PJ. Triptan signal transduction. In: Olesen J, Tfelt-Hansen P, Welch KMA, et al., editors. The headaches. Chap. 21. 3rd ed. Pennsylvania: Lippincott Williams & Wilkins, 2006: 203–211

    Google Scholar 

  19. Tfelt-Hansen P, DeVries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs 2000; 60(6): 1259–87

    Article  PubMed  CAS  Google Scholar 

  20. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia 2002; 22(7): 491–512

    Article  PubMed  CAS  Google Scholar 

  21. Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2004; (1): CD002286; 1-10

  22. Barsby RW, Salan U, Knight DW, et al. Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon ses-quiterpene lactone content. Planta Med 1993; 59(1): 20–5

    Article  PubMed  CAS  Google Scholar 

  23. Bejar E. Parthenolide inhibits the contractile responses of rat stomach fundus to fenfluramine and dextroamphetamine but not serotonin. J Ethnopharmacol 1996; 50(1): 1–12

    Article  PubMed  CAS  Google Scholar 

  24. Mittra S, Datta A, Singh SK, et al. 5-Hydroxytryptamine-inhibiting property of feverfew: role of parthenolide content. Acta Pharmacol Sin 2000; 21(12): 1106–14

    PubMed  CAS  Google Scholar 

  25. Weber JT, O’Connor MF, Hayataka K, et al. Activity of parthenolide at 5HT2A receptors. J Nat Prod 1997; 60(6): 651–3

    Article  PubMed  CAS  Google Scholar 

  26. Shrivastava R, John GW. Ligand binding study of the interaction of Tanacetum parthenium and Salix alba with 5-HT receptors associated with headache. 2006 (Submitted for publication)

  27. Headache Classification Committee of the International Headache Society. ICHD-II. Cephalalgia 2004; 24Suppl. 1: 1–160

    Google Scholar 

  28. Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988; II(8604): 189–92

    Article  Google Scholar 

  29. Diener HC, Pfaffenrath V, Schnitter J, et al. Efficacy and safety of 6.25mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention: a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia 2005; 25(11): 1031–41

    Article  PubMed  CAS  Google Scholar 

  30. Johnson ES, Kadam NP, Hylands DM, et al. Efficacy of feverfew as prophylactic treatment of migraine. BMJ 1985; 291(6495): 569–73

    Article  PubMed  CAS  Google Scholar 

  31. DeWeerdt CJ, Bootsma HPR, Hendricks H. Herbal medicines in migraine prevention: randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine 1996; 3: 225–30

    Article  PubMed  Google Scholar 

  32. Pfaffenrath V, Diener HC, Fischer M, et al. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis: a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia 2002; 22(7): 523–32

    Article  PubMed  CAS  Google Scholar 

  33. Diener HC. Placebo and headache [abstract]. Cephalalgia 2005; 25: 841

    Article  Google Scholar 

  34. Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytother Res 1997; 11: 508–11

    Article  Google Scholar 

  35. Khayyal MT, El-Ghazaly MA, Abdallah DM, et al. Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract. Arzneimittel Forschung 2005; 55(11): 677–87

    PubMed  CAS  Google Scholar 

  36. Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. J Pharm Pharmacol 1990; 42(8): 553–7

    Article  PubMed  CAS  Google Scholar 

  37. Reuter U, Chiarugi A, Bolay H, et al. Nuclear factor-kappaB as a molecular target for migraine therapy. Ann Neurol 2002; 51(4): 507–16

    Article  PubMed  CAS  Google Scholar 

  38. Kwok BH, Koh B, Ndubuisi MI, et al. The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 2001; 8(8): 759–66

    Article  PubMed  CAS  Google Scholar 

  39. Tassorelli C, Greco R, Morazzoni P, et al. Parthenolide is the component of Tanacetum parthenium that inhibits nitroglycerin-induced Fos activation: studies in an animal model of migraine. Cephalalgia 2005; 25(8): 612–21

    Article  PubMed  CAS  Google Scholar 

  40. Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 2004; 55(1): 19–26

    Article  PubMed  CAS  Google Scholar 

  41. Tfelt-Hansen P, Block G, Dahlof C, et al. Guidelines for controlled trials of drugs in migraine, 2nd ed. Cephalalgia 2000; 20(9): 765–86

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The study was sponsored by the Naturveda — Vitro-Bio Research Institute. Dr J.C. Pechadre received an honorarium for this work from The Vitro-Bio Research Institute. This paper is dedicated to Dr Pechadre’s memory.

The other authors have no potential conflicts of interest that are directly relevant to the contents of this study.

Author information

Authors and Affiliations

  1. Naturveda - Vitro-Bio Research Institute, ZAC de Lavaur, 63500, Issoire, France

    R. Shrivastava &  G. W. John

  2. Department of Neurology, EEG and Functional NS Exploration, Hotel Dieu, Clermont Ferrand, France

    J. C. Pechadre

Authors
  1. R. Shrivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. C. Pechadre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. W. John
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. W. John.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shrivastava, R., Pechadre, J.C. & John, G.W. Tanacetum parthenium and Salix alba (Mig-RL®) Combination in Migraine Prophylaxis. Clin. Drug Investig. 26, 287–296 (2006). https://doi.org/10.2165/00044011-200626050-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200626050-00006

Keywords

Search

Navigation