Feverfew (Tanacetum parthenium) as a tool for helping with Migraine

This systematic review of 19 randomised controlled trials of single-ingredient herbal migraine treatments examined feverfew (Tanacetum parthenium) among others, finding mixed evidence for feverfew and identifying herbal medicines as potential options to enhance migraine treatment.

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.

This review of feverfew (Tanacetum parthenium) summarises its traditional use in rheumatism, fever, migraine and menstrual pain and the preclinical and clinical evidence that its sesquiterpene lactone parthenolide underlies its safe and effective prevention of migraine attacks.

This review of feverfew (Tanacetum parthenium) documents its traditional uses (fever, migraine, rheumatoid arthritis, menstrual problems), its sesquiterpene-lactone (parthenolide) and flavonoid constituents, and its anticancer, anti-inflammatory, antispasmodic and emmenagogue pharmacology.

This systematic review of six randomised double-blind placebo-controlled trials found that the majority favour feverfew (Tanacetum parthenium) over placebo for migraine prevention, with only mild transient adverse effects, concluding feverfew is likely effective and safe for migraine prophylaxis.

This Cochrane systematic review of four randomised placebo-controlled trials found that most suggested beneficial effects of feverfew (Tanacetum parthenium) for migraine prevention, though the highest-quality trial found no significant difference, concluding efficacy is not 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.

In a double-blind multicentre randomised placebo-controlled dose-response study of the feverfew CO2-extract MIG-99 (n=147), a predefined subgroup with frequent migraine showed a dose-dependent reduction in attack frequency, with 6.25 mg three times daily giving the most favourable benefit-risk ratio and tolerability comparable to placebo.

In a prospective open-label study of 12 migraine patients, a combination of Tanacetum parthenium (feverfew) and Salix alba (white willow) reduced migraine attack frequency by ~62%, intensity by ~63% and duration by ~76% over 12 weeks, with good tolerability and improved quality of life.