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

R. Shrivastava; J.C. Pechadre; G.W. John

Disclosures

Clin Drug Invest. 2006;26(5):287-296. 

In This Article

Abstract and Introduction

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.

Headache is one of the most common human medical complaints. During a given 12-month period most people will experience a headache.[1] The overall prevalence of migraine is 11%: 6% among men and 15–18% among women,[2] but an estimated 50% of all migraineurs are not even diagnosed.[3] Despite major recent advances in our understanding of migraine pathophysiology, migraine treatment is far from being satisfactory. Less than half the patients who are treated with a serotonin 5-HT1B/1D receptor agonist (triptan) drug become free of pain 2 hours later.[4] In patients with more than two migraine attacks per month, current prophylactic treatment reduces the number of attacks by up to 50%, but in only half the patients.[5] Moreover, undesirable effects encountered with prophylactic drugs are largely responsible for the high rates of treatment discontinuation.[5] There is still no effective prophylactic drug available that has specifically been developed for migraine.[2,5,6] Clearly, therefore, more effective and better tolerated prophylactic treatments for migraine are required.

Migraine is best understood as a primary disorder of the brain[2] and trigeminovascular system activation is now widely accepted as being involved in the nociceptive process by central sensitisation, sensory neuropeptide release and vasodilatation of cranial blood vessels.[2,7,8] However, the initial events that actually trigger trigeminovascular activation are not well understood.[8,9,10,11] Serotonin has been consistently implicated in migraine,[12,13,14,15,16] which is suggestive too of a role for its receptors. In particular, 5-HT1B and 5-HT1D receptors are considered to be the main molecular targets of sumatriptan and congeners in acute treatment,[17,18,19] whereas 5-HT2A and 5-HT2C receptors are targeted by 5-HT antagonists, such as methysergide, oxetorone, pizotifen and cypro-heptadine, which are used in migraine prophylaxis.[5,6,14,20]

Tanacetum parthenium (feverfew) has traditionally been used as a well tolerated prophylactic treatment for migraine, but its clinical effectiveness remains to be fully established,[20,21] suggesting that T. parthenium alone may be insufficient to provide conclusive benefit. The mechanism of action of T. parthenium is not well understood, but 5-HT-receptor-blocking properties have been reported,[22,23,24,25] and inhibition of binding to 5-HT2A and 5-HT2C receptors, and to a lesser extent 5-HT1B receptors,[26] has been suggested to play a role. In the same study, T. parthenium did not recognise 5-HT1D receptors.[26] Interestingly, Salix alba (white willow), which has been traditionally used to relieve various pains including headache, was shown to strongly inhibit binding to 5-HT2A and 5-HT2C receptors in similar fashion to T. parthenium.[26] However, in marked contrast to T. parthenium, S. alba interacted strongly with 5-HT1D receptors,[26] and combination of the two plant extracts consolidated activity at 5-HT2A and 5-HT2C receptors whilst maintaining activity at 5-HT1D receptors.[26] The possibility is thus raised that combining T. parthenium with S. alba may provide more effective migraine prophylaxis than T. parthenium alone. A prospective, open-label study was therefore carried out to evaluate the efficacy of 12 weeks' treatment with standardised T. parthenium and S. alba extracts in combination (Mig-RL®; Naturveda – Vitro-Bio Research Institute, Issoire, France)1 on attack frequency (primary efficacy criterion), pain intensity and duration (secondary efficacy criteria) in 12 patients diagnosed as having migraine without aura.

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