Feverfew (Tanacetum parthenium) and Migraine: evidence and sources

Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted. Studies were identified through electronic database searches on Medline (Pubmed), Cochrane Library, Scopus, and CINAHL. Nineteen studies were identified examining the effects on migraine of feverfew, butterbur, curcumin, menthol/peppermint oil, coriander, citron, Damask rose, chamomile, and lavender. Overall, findings on the efficacy of feverfew were mixed and there was positive, albeit limited evidence for butterbur. There were positive, preliminary findings on curcumin, citron, and coriander as a prophylactic treatment for migraine, and the use of menthol and chamomile as an acute treatment. However, the risk of bias was high for many studies. The results of this systematic review suggest that several herbal medicines, via their multifactorial physiological influences, present as potential options to enhance the treatment of migraine. However, further high-quality research is essential to examine their efficacy and safety as a treatment for migraine.

Background This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Feverfew for preventing migraine' (2004, Issue 1). Feverfew (Tanacetum parthenium L.) extract is a herbal remedy, which has been used for preventing attacks of migraine. Objectives To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew monopreparations versus placebo for preventing migraine. Search methods For this updated version of the review we searched CENTRAL, MEDLINE, EMBASE and AMED to January 2015. We contacted manufacturers of feverfew and checked the bibliographies of identified articles for further trials. Selection criteria We included randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew monopreparations for preventing migraine in patients of any age. We included trials using clinical outcome measures, while we excluded trials focusing exclusively on physiological parameters. There were no restrictions regarding the language of publication. Data collection and analysis We systematically extracted data on patients, interventions, methods, outcome measures, results and adverse events. We assessed risk of bias using the Cochrane 'Risk of bias' tool and evaluated methodological quality using the Oxford Quality Scale developed by Jadad and colleagues. Two review authors (BW and MHP for this update, MHP and EE for the original version) independently selected studies, assessed methodological quality and extracted data. We resolved disagreements concerning evaluation of individual trials through discussion. Main results We identified one new study for this update, resulting in six trials (561 patients) meeting the inclusion criteria. Five of the six trials reported on the main outcome, migraine frequency. Although five of the trials were generally of good methodological quality, all studies were either of unclear or high risk of bias with regards to sample size. Pooled analysis of the results was not possible due to the lack of common outcome measures and heterogeneity between studies in terms of participants, interventions and designs.The most recent trial added to this version of the review is rigorous and larger (n = 218), using a stable feverfew extract at a dose determined by a previous dose-finding trial. It reports that feverfew reduced migraine frequency by 1.9 attacks from 4.8 to 2.9 and placebo by 1.3 from to 4.8 to 3.5 per month, resulting in a difference in effect between feverfew and placebo of 0.6 attacks per month. For the secondary outcome measures intensity and duration of migraine attacks, incidence and severity of nausea and vomiting, and global assessment no statistically significant differences were reported. Results of previous trials are not convincing: three trials reporting positive effects of feverfew are all of small sample size (17 to 60 participants), while two rigorous trials (n = 50, 147) did not find significant differences between feverfew and placebo. Only mild and transient adverse events, most commonly gastrointestinal complaints and mouth ulcers, were reported in the included trials. Authors' conclusions Since the last version of this review, one larger rigorous study has been included, reporting a difference in effect between feverfew and placebo of 0.6 attacks per month. This adds some positive evidence to the mixed and inconclusive findings of the previous review. However, this constitutes low quality evidence, which needs to be confirmed in larger rigorous trials with stable feverfew extracts and clearly defined migraine populations before firm conclusions can be drawn. It appears from the data reviewed that feverfew is not associated with any major safety concerns.

Feverfew was already known at the beginning of our era. In folk medicine, infusions from the leaves of Tanacetum parthenium were used in rheumatism, fever, and in migraine, menstrual pain, toothaches also digestive troubles, cough, or parasitic diseases. It has been proved that the biological activity of the plants resultsfrom the presence of the chemical compounds with different structures, including the the sesquiterpene lactones, which include partenolid, determining the antimigraine properties of plants. Research up to date on preclinical and clinical nature demonstrate the efficacy of plants in the prevention of migraine attacks. Based on the results can also conclude that the use of feverfew is safe and recorded side effects are mild and transient.

Feverfew (Tanacetum parthenium L.) (Asteraceae) is a medicinal plant traditionally used for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomach aches, toothaches, insect bites, infertility, and problems with menstruation and labor during childbirth. The feverfew herb has a long history of use in traditional and folk medicine, especially among Greek and early European herbalists. Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting. The plant contains a large number of natural products, but the active principles probably include one or more of the sesquiterpene lactones known to be present, including parthenolide. Other potentially active constituents include flavonoid glycosides and pinenes. It has multiple pharmacologic properties, such as anticancer, anti-inflammatory, cardiotonic, antispasmodic, an emmenagogue, and as an enema for worms. In this review, we have explored the various dimensions of the feverfew plant and compiled its vast pharmacologic applications to comprehend and synthesize the subject of its potential image of multipurpose medicinal agent. The plant is widely cultivated to large regions of the world and its importance as a medicinal plant is growing substantially with increasing and stronger reports in support of its multifarious therapeutic uses.

Objective Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often advocated for the prevention of migraine. The aims of this systematic review are to update the evidence from rigorous clinical trials for or against the efficacy of feverfew for migraine prevention and to provide a safety profile of this herbal remedy. Design Literature searches were performed using the following databases: Medline, Embase, Biosis, CISCOM and the Cochrane Library (all from their inception to December 1999). Only randomized, placebo-controlled, double-blind trials of feverfew mono-preparations for the prevention of migraine in human subjects were included. All articles were read by two independent reviewers. Data were extracted in a pre-defined, standardized fashion. The methodological quality of the trials was evaluated by the Jadad score. For the assessment of safety issues, major reference texts were also consulted. Results Six trials met the inclusion/exclusion criteria. The majority favour feverfew over placebo. Yet important caveats exist. The data also suggest that feverfew is associated with only mild and transient adverse effects and few other safety concerns. Conclusions Feverfew is likely to be effective in the prevention of migraine. There are no major safety problems.

Background Feverfew (Tanacetum parthenium L.) is a popular herbal remedy for migraine. Objectives To systematically review the evidence for or against the efficacy of feverfew versus placebo for the prevention of migraine. Search strategy Electronic literature searches were performed using the databases CISCOM (Research Council for Complementary Medicine, London, UK), MEDLINE, EMBASE, Biosis and the Cochrane Library (each from its inception to April 1998). Manufacturers were contacted and the bibliographies of identified articles checked for further trials. Selection criteria Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. No restrictions regarding the language of publication were imposed. Data collection and analysis Data on patients, interventions, methods, outcomes and results were extracted in a pre-defined, standardised manner. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Both data extraction and the assessment of methodological quality were performed independently by two reviewers. Main results Four trials met the inclusion criteria. The majority of these trials suggested beneficial effects of feverfew compared with placebo. However, the trial with the highest methodological quality, which was also among the largest, found no significant difference between feverfew and placebo. Reviewer's conclusions The efficacy of feverfew for the prevention of migraine has not been established beyond reasonable doubt.

Tanacetum parthenium (TP) is a member of the Asteracee family long used empirically as a herbal remedy for migraine. So far, however, clinical trials have failed to prove consistently the effectiveness of TP extracts in preventing migraine attacks, probably as a consequence of the uncertainty as regards the active principle. In this study, the biological effects of different TP extracts and purified parthenolide were tested in an animal model of migraine based on the quantification of neuronal activation induced by nitroglycerin. The extract enriched in parthenolide significantly reduced nitroglycerin-induced Fos expression in the nucleus trigeminalis caudalis. Purified parthenolide inhibited nitroglycerin-induced neuronal activation in additional brain nuclei and, significantly, the activity of nuclear factor-kappaB. These findings strongly suggest that parthenolide is the component responsible for the biological activity of TP as regards its antimigraine effect and provide important information for future controlled clinical trials.

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.

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-HT(2A/2C) receptors; T. parthenium failed to recognise 5-HT(1D) 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 300 mg plus S. alba 300 mg (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 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.