The Efficacy and Safety of Tanacetum Parthenium (Feverfew) in Migraine Prophylaxis—a Double-Blind, Multicentre, Randomized Placebo-Controlled Dose-Response Study

Abstract

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.

The Effect of Feverfew Cultivated in Iran for the Prophylactic Treatment of Migraine: A Randomized Placebo-controlled Clinical Trial

“…In some previous clinical trials, the effect of feverfew as a migraine prophylaxis was studied (10,11). In one study in Germany, the results indicated that the extract of feverfew with a dosage of three capsules of 6.25 mg per day reduced the migraine attacks per month (11).…”

“…In one study in Germany, the results indicated that the extract of feverfew with a dosage of three capsules of 6.25 mg per day reduced the migraine attacks per month (11). In a clinical trial, 72 migraine patients received dried feverfew leaves (82 mg) or placebo per day for four months.…”

“…There are a number of clinical trials demonstrated efficacy and safety of feverfew in migraine prophylaxis. Studies showed a good effect of feverfew in the prophylactic treatment of migraine while there is no report of serious side effects in clinical trials (10)(11)(12). According to previous investigations the active compounds of feverfew are sesquiterpene lactones principally parthenolide.…”

Development of enteric coated tablets from spray dried extract of feverfew (Tanacetum parthenium L: )

“…Nowadays it is a recommended therapeutic treatment for migraine prophylaxis (Khan et al, 2003). Although the pathophysiology of migraine is not yet fully understood, its symptoms are reported by 15% of females and 6% of males in the adult age, from 35 to 45 years (Pfaffenrath, 2002). Clinical trials have demonstrated the high effectiveness of feverfew against headache and other symptoms linked to migraine (Palevith, 1997).…”

A proposal for the quality control of Tanacetum parthenium (feverfew) and its hydroalcoholic extract

“…The commonly used feverfew extracts trigger the release of serotonin (5-HT) from platelets, thus inducing a wide variety of aggregation agents (Pfaffenrath et al, 2002). The effi cacy of the extract in migraine prophylaxis was also assessed in randomized, placebo-controlled, double-blind and cross-over clinical studies (Gruenwald et al, 2000).…”