An Extract of Petasites hybridus is Effective in the Prophylaxis of Migraine

Alternative Medicine Review, June, 2001 by Werner Grossmann, Hanns Schmidramsl

ABSTRACT

OBJECTIVE: Migraine is still an unsolved problem. This clinical trial investigates the efficacy and tolerance of Petasites hybridus in the prophylaxis of migraine. METHODS: A randomized, group-parallel, placebo-controlled, double-blind clinical study was carried out with a special [CO.sub.2] extract from the rhizome of Petasites hybridus. Following a four-week run-in phase, 60 patients received either the special Petasites hybridus extract Petadolex or placebo at a dosage of two capsules (each capsule contains 25 mg) twice daily over 12 weeks. Outcome variables included the frequency, intensity and duration of migraine attacks as well as any accompanying symptoms. RESULTS: The frequency of migraine attacks decreased by a maximum of 60 percent compared to the baseline. This reduction in migraine attacks with Petadolex was significant (p [is less than] 0.05) compared to placebo. No adverse events were reported. Petasites was exceptionally well tolerated. CONCLUSIONS: The results suggest that migraine patients can benefit from prophylactic treatment with this special extract. The combination of high efficacy and excellent tolerance emphasizes the particular value that Petasites hybridus has for the prophylactic treatment of migraine.

(Altern Med Rev 2001;6(3):303-310

Introduction

The pathophysiology of migraine is still an unsolved problem. In the past, a so-called vascular hypothesis and a neurogenic hypothesis dominated. For Thomas Willis,[1] the basis of migraine was a disturbance of cerebral circulation.[1] Liveing,[2] on the other hand, considered the vascular component to be of secondary importance.[2] He associated this painful phenomenon with an epileptiform activity or "nerve storms." In 1938, Wolff and co-workers formulated the vascular hypothesis by proposing that migraine headache is caused by vasodilatation of the extracranial vessels, whereas neurological symptoms result from intracranial vasoconstriction.[3]

In the last years, new data brought these two hypotheses into discussion, suggesting that migraine headache develops primarily from yet unidentified metabolic or neurophysiological events, closely associated with the distribution of trigeminal nerve fibres innervating meningeal vessels, on the one hand, and leading to an increased activity of the serotonergic raphe nuclei in the brain stem, on the other hand.[4] In a further step, a vasoconstrictive/vasodilatory process does indeed take place, but it remains unclear whether the process takes place at the same time and in the same vessel.[5-7] The increased serotonergic activity and maximal vasodilatation lead to a process in which a large number of different substances are involved, e.g. [PGE.sub.2], polypeptide neurotransmitters, albumin, as well as endorphin, histamine, substance P, arachidonic acid, extravasation of lymphocytes and so on.[8,9]

Altogether, this results in a sterile neurogenic inflammation -- a process that gives us today a much better understanding of different metabolic disturbances. In the case of migraine, neurogenic inflammation stimulates the pain-mediating C fibers, which then project the increased activity back to the trigeminal nerve system. What emerges from this picture is that vasoconstriction and neurogenic inflammation are two main steps in the generation of migraine headache.

Petasites hybridus is a remedy that can be traced back about 900 years, and has been used safely and effectively in modern medicine since the middle of the century. Its pain-relieving effect has been demonstrated in clinical reports of patients receiving the preparation for several weeks.[10-16]

Petadolex is an extract of the rhizome from Petasites hybridus, and petasine and isopetasine are the main components.[17] It has been shown that petasine and isopetasine are strong vasodilatory substances, whereby this effect on smooth muscle preparations in vitro is equivalent to papaverine.[18,19] Even more important may be the finding from pharmacological studies that both components exert a highly potent anti-inflammatory effect through inhibition of leukotriene synthesis.[20,21] These clinical and experimental findings served as the pharmacological basis of the present clinical study to confirm the efficacy and tolerability of Petasites hybridus in the prophylaxis of migraine with and without aura.

Methods and Patients

The trial was conducted as a randomized, group-parallel, placebo-controlled, double-blind clinical study. It consisted of a four-week run-in phase with no trial medication, followed by a 12-week therapy phase during which either Petasites hybridus (Petadolex, Weber & Weber GmbH & Co. KG, Germany) or placebo was administered at a dosage of two capsules twice daily. Each capsule of the trial drag contained 25 mg of a [CO.sub.2] extract from the rhizome of Petasites hybridus. The extraction method achieves a reduction in the quantity of pyrrolizidine alkaloids to below the detection limit. This meets the requirement of the German Health Authority; i.e., the BfArM (Bundesinstitut fur Arzneimittel und Medizinprodukte).[22]