Date Last Updated: 27/10/04

Feverfew for the prevention and treatment of migraine

Overview

A migraine is a severe headache that can last up to 24 hours. Feverfew is a plant often used in herbal medicine for preventing and treating migraines. This evidence summary identified three systematic reviews and six clinical trials (that included between 17-147 people - a total of 363 people) on the use of feverfew for migraines. All three reviews concluded that overall feverfew does not help in the prevention or treatment of migraines. In the two most well-designed trials feverfew had no effect on the majority of symptoms associated with migraine. There is some evidence that the number of migraine attacks decreases as the dose of feverfew increases, but only for those people that experience more than four migraine attacks per month. The poorer quality trials found that feverfew reduced the frequency of migraine, the occurrence of nausea and vomiting associated with migraine, and the severity of nausea, vomiting, pain and sensitivity to light and noise associated with migraine. Mild but reversible side effects (such as mouth ulceration, stomach complaints or contact allergy to the plant) can occur with feverfew. No serious side effects have been reported.

Background

Migraine
A migraine is an episodic headache, typically occurring on one side of the head¹, which lasts between 6-24 hours². Migraines are sometimes preceded by an aura (a warning or sensation experienced before the start of a migraine headache)². Symptoms of a migraine include severe headache and/or temporary visual, neurological, or gastrointestinal disturbances³. The aim of a preventive treatment for migraine is to prevent or reduce the frequency of new migraine attacks from occurring, to improve response to acute medications, to improve patient function, and to reduce disability from the condition⁴.

Feverfew
Feverfew (Tanacetum parthenium L) is a perennial herb growing to about 14-45 cm in height⁵. It is commonly found in gardens and along roadsides in New Zealand. The stem is upright, hairy, branching and finely furrowed. Leaves are feather-like, yellow-green, aromatic, toothless, hairless, and divided into broad lobed segments. Daisy-like flowers are white with yellow centres^{5, 6}. Feverfew is also referred to as Altamisa, Bachelor's Buttons, Motherherb, Featherfew, Chamomile Grande, Featherfoil, Febrifuge Plant, Midsummer Daisy, Mutterkraut, Nosebleed, Santa Maria, Wild Chamomile, Wild Quinine, or Chrysanthemum parthenium^{2, 6}. Feverfew has a long history of traditional use, particularly for conditions associated with fevers, inflammatory conditions, psoriasis, toothache, insect bites, rheumatism, asthma and stomach ache⁷. More recently it has been used as a remedy for preventing and treating migraines.

The pharmacological properties of feverfew have been extensively investigated but remain unclear. Parthenolide seems to be considered the main active ingredient⁸, although other constituents may also play a role^{9, 10}. Pure parthenolide as a preventive treatment for migraine has yet to be tested in a clinical trial. Commercially available preparations of feverfew (in the form of tablets or capsules taken orally) are usually made up of dried leaf, but can also include stem and flower heads.

The level of parthenolide and other compounds in feverfew preparations has been reported to vary significantly. Some feverfew products have been found to contain little or no active compounds, while in many preparations that do contain active ingredients, the concentration is unknown. The quantity of active compounds in individual plants, plant parts, and fresh and dried preparations is known to vary greatly. For people that chose to use feverfew for the management of migraine, the Canadian Health Protection Branch of the Canadian government currently recommends a dosage of 125 mg of feverfew per day, with each dosage unit containing at least 0.2% parthenolide¹¹.

Feverfew can be obtained as an “over the counter” product from health food shops, supermarkets, pharmacies, etc. A medical herbalist may also prescribe feverfew. The practice of herbal medicine is not currently regulated by legislation in New Zealand, however many herbal medicine practitioners are affiliated with a self-regulated professional body (such as the New Zealand Association of Medical Herbalists).

Evidence reviewed in this summary

Efficacy information

Systematic reviews: Three systematic reviews on this topic were identified for this evidence summary^{7, 8, 12}. The first review⁸ included five clinical trials (one of which was an abstract¹³). The second review⁷ is an update of the first and included six clinical trials (two of which were abstracts^{13, 14}). The third review is by the Cochrane Collaboration, with the most recent update conducted on the 18th November 2003¹². This review included the same four clinical trials as the first review, but not the abstract. The reviews only searched five databases so some trials may have been missed.
Clinical trials: The above reviews identified six double-blind, randomised, placebo-controlled trials, involving between 17-147 people - a total of 363 people^{9, 13-18}. One of the trials was only reported as an abstract¹³, and another trial was initially available only as an abstract¹⁴ (and was included in the second review mentioned above), but has recently been published in full¹⁸. No clinical trials of feverfew for migraine are known to be currently underway see (http://www.controlled-trials.com).
Case-control studies/Cohort studies/Case studies: Given the extensive coverage of the above systematic reviews, no case-control, cohort or case studies were assessed for this evidence summary.

Safety information

Systematic reviews/Clinical trials: The above three systematic reviews^{7, 8, 12} reported information on side effects associated with the use of feverfew for the prevention and treatment of migraine. However, only three^15,16,18 of the six trials^{9, 13-18} identified by the reviews provided actual data on side effects.
Other studies: Given the comprehensive information provided by the above studies, no further information on side effects was sought.

Evidence on efficacy

Evidence on the use of feverfew for the prevention and treatment of migraines is available from three reviews^{7, 8, 12} (summarizing results from six trials^{9, 13-18}). All three reviews stated that overall there is insufficient evidence to conclude that feverfew has any effect on the prevention or treatment of migraine. Three trials on feverfew for migraine used poor scientific methods^15-17, and four trials did not use a standard feverfew preparation, involved less than 100 people, and had differing treatment periods^{9, 15-17}. Results from the individual trials are given below:

The most recent and largest trial published (147 participants), was reasonably well-conducted in terms of scientific validity, and ran for 12 weeks¹⁸. This trial found no clear difference in outcomes between feverfew and placebo, for three different doses of feverfew. The outcomes assessed included total number of migraine attacks in the last 28 days of treatment, total and average duration and intensity of migraine, overall migraine severity, number of days with accompanying migraine symptoms, number of missed working days due to migraine, mean duration of confinement to bed due to migraine, mean duration of a single attack, and type and amount of additionally taken medications for the treatment of migraine attacks.
The above trial reported that in a subgroup of 49 people who experienced more than four migraine attacks per month, the frequency of migraine attacks decreased as the dose of feverfew increased¹⁸.
Another reasonably well-conducted but small trial (50 participants) reported no clear difference in the frequency and severity of headache, between the feverfew and placebo group⁹.
Three trials (with between 17-72 participants) are considered to be of poor scientific quality^15-17. These trials found that feverfew:
- Had no effect on the duration of migraine attacks or migraine severity¹⁶
- Reduced the occurrence of nausea and vomiting associated with migraine^{15, 16}
- Reduced the severity of nausea, vomiting, pain, sensitivity to light, and sensitivity to noise associated with migraine¹⁷
- Reduced the number of migraine attacks^{15, 16}

Evidence on safety

Findings from the three systematic reviews^{7, 8, 12} and three clinical trials^15,16,18 reviewed for this summary, indicate that:

Side effects associated with the use of feverfew have been reported. For instance, in one trial, four of the eight patients taking feverfew experienced a side effect¹⁵. In comparison all nine people taking the placebo reported side effects. In another trial, 134 side effects were reported by 52 (35%) of the 147 patients that were included in the safety analysis¹⁸.
Reported side effects tend to be mild and reversible, and include mouth ulceration or inflammation, mild stomach complaints, and contact allergy to the plant⁷.
Some people also experience “post-feverfew syndrome” which includes headache, tension, tiredness and nervousness¹⁵.

Cited references

To find out more about any of the references listed below go to the "About page" of this website and read the section titled "How can referenced articles be obtained."

Gawel MJ. The use of feverfew in the prophylaxis of migraine attacks. Today's Therapeutic Trends 1995;13(2):79-86.
Ernst E, Pilter M, Stevinson C, White A. The desktop guide to Complementary and Alternative Medicine: an evidence-based approach. London: Mosby; 2001.
Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia. 2002;22(7):491-512.
Silberstein SD, Freitag FG. Preventive treatment of migraine. Neurology 2003;60(7):S38-S44.
Berry M. Feverfew. Pharmaceutical Journal 1994;253(6818):806-808.
Awang DVC. Herbal Medicine: Feverfew. Canadian Pharmaceutical Journal 1989;122(5):266-270.
Ernst E, Pittler MH. The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutrition. 2000;3(4A):509-514.
Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalalgia. 1998;18(10):704-708.
de Weerdt CJ, de Bootsma HPR, Hendriks H. Herbal medicines in migraine prevention. Randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine 1996;3(3):225-230.
Brown AMG, Edwards CM, Davey MR, Power JB, Lowe KC. Pharmacological activity of feverfew (Tanacetum parthenium (L) Schultz-Bip): Assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence in-vitro. Journal of Pharmacy and Pharmacology 1997;49(5):558-561.
Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. American Journal of Health-System Pharmacy. 1999;56(2):125-138; quiz 139-141.
Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine. Cochrane Database of Systematic Reviews 2002;1.
Kuritzky A, Elhacham Y, Yerushalmi Z, Hering R. Feverfew in the treatment of migraine - its effect on serotonin uptake and platelet activity. Neurology 1994;44(4):A201-A201.
Pfaffenrath V, Fischer M, Friede M, Heinneicke V, Zepelin H. Clinical dose-response study for the investigation of efficacy and tolerability of Tanacetum parthenium in migraine prophylaxis. In: Proceedings of Deutscher Schmerzkongress; 1999.
Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. British Medical Journal Clinical Research Ed. 1985;291(6495):569-573.
Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet. 1988;2(8604):189-192.
Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytotherapy Research 1997;11(7):508-511.
Pfaffenrath V, Diener HC, Fischer M, Friede M, Henneicke-von Zepelin HH, Investigators. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia. 2002;22(7):523-532.

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