Feverfew for Prevention of Migraine
By Harley Goldberg, DO
April 1999; Volume 2: 41-43
Is there something more you can do for your migraine patient? Is there another alternative to the prophylactic drugs? Enough evidence exists to say "Yes, migraine sufferers may want to consider feverfew."
Botany
Feverfew has had numerous botanical names, including Tanacetum parthenium, aka chrysanthemum parthenium, pyrethrum parthenium, matricaria parthenium, and leucanthemum parthenium. A member of the daisy family Asteraceae (previously Compositae), feverfew is a short perennial that grows in fields and meadows and along roadsides. The round, daisy-like flowers have yellow disks and 10-20 white-toothed rays. The leaf is generally used in herbal preparations, although some formulations include all aerial parts.
History
Feverfew has been grown in gardens in Europe for centuries. Currently feverfew is a popular herbal remedy for prevention and treatment of migraine. In traditional and folk use, feverfew is touted for multiple ailments. Its use as a febrifuge (that which reduces fever) gave rise to the common name feverfew.1 Nicholas Culpeper, the famous early 17th century physician, claimed its virtues "to strengthen and cleanse the womb, expels the afterbirth, and does a woman all the good she can desire of an herb." He also noted feverfew’s usefulness to promote menstruation, for cough and chest colds, for "melancholy or heaviness, and sadness of spirits," for vertigo and headache, and against excess opium use.2 Other traditional uses include colic, flatulence, general indigestion, expelling worms, hysteria, and suppressed urine,3 as well as a topical application for insect bites and a general purpose insect repellent when planted around a house or garden.4
Pharmacology
Feverfew is rich in sesquiterpene lactones, and of these, especially parthenolides, although there is debate as to whether the parthenolide content has any bearing on clinical efficacy.5 In animal experiments, feverfew inhibits prostaglandin, thromboxane, and leukotriene synthesis; it also impedes platelet aggregation and histamine release. It reduces serotonin release from thrombocytes and polymorphonuclear leukocytes.6,7
Mechanism of Action
The precise mechanism by which feverfew may prevent migraine headaches is not clear. Although there is in vitro evidence of inhibition of prostaglandin synthesis, neither the leaf extracts nor the whole plant act as cyclooxygenase inhibitors in the arachidonic acid cascade, the mechanism of salicylates.
Clinical Trials
There are two randomized, placebo-controlled trials of feverfew for prevention of migraine. In one London clinic, Johnson et al enrolled patients with a diagnosis of common or classic migraine, a history of at least two years duration, not more than eight attacks per month, and self-prescribed continuous daily use of feverfew for at least three months.8 Seventeen of 20 patients agreed to participate.
Patients were randomized to receive 50 mg of dried feverfew or placebo for six periods of four weeks. The authors were fastidious in the preparation of equivalent feverfew capsules, using leaves harvested in a single batch from the same garden. The contents of both active and placebo bottles were sprinkled with 1-2 mg of feverfew powder so that opening both active and placebo capsules gave identical smells. Patients reported symptoms on diary cards, grading severity and duration. Use of usual drug treatment for acute attacks was also recorded. The group taking placebo showed significant increase in migraine attacks, while the group using feverfew showed no significant change in frequency or severity of attacks. Two patients in the placebo group discontinued the study before completion because their symptoms increased.
Murphy et al conducted a prospective randomized, double-blind, placebo-controlled trial of feverfew for migraine prophylaxis.9 Seventy-two patients who reported at least two years duration of at least one migraine per month were randomized to receive feverfew powdered leaves standardized to anti-secretory activity as measured by C-serotonin release from human platelets (70-114 mg feverfew equivalent standardized to 2.19 mcg parthenolide). After a one-month placebo run, patients were randomized to feverfew or placebo. At four months and without a washout period, patients were crossed over to four months of the opposite arm.
There was a 24% reduction in the number of attacks during feverfew treatment, but no significant change in the duration of individual attacks. There was a significant reduction in associated nausea and vomiting and a nonsignificant trend toward reduction in attack severity. Global assessments of efficacy were measured by visual analogue scale ("worst ever" to "best ever") as well as A ("much worse") to E ("much better"). Both assessments showed that feverfew was better than placebo.
It should be noted that these studies are at times cited as support for feverfew treatment of migraine, but neither study involves an arm of active treatment for acute attacks. Also of note is that routine hematological and blood chemistry, urine analysis, blood pressure, and pulse revealed no abnormalities in either clinical trial described above.
Although pharmacological studies, case reports, and essays exist, other good clinical trials could not be located. A thorough review of efficacy and safety is available from the U.S. Pharmacopoeia.7
Dosage/Formulation
Recommended dosage is 50 mg dried leaf or 2-3 fresh leaves per day. The leaves and above ground parts can be used. Although the most common standardization is to parthenolide content, there is evidence that this measure does not translate into any meaningful clinical effect.5 Feverfew is available as dried powder in capsules and is sometimes prepared as an infusion, using between 50 mg and 1.2 g of leaf powder, taken internally. (See Table 1 for price comparison of feverfew preparations.)
| Table 1 | ||
| Price comparison of feverfew preparations_______________________________________________ | ||
| Manufacturer | Per Capsule Formulation | Price/Count |
| Twinlab | 125 mg feverfew | $18.50/ 100 capsules |
| Nutritional Dynamics | 250 mg feverfew leaf standardized to 0.7% parthenolide | $11.95/ 60 capsules |
| Nature’s Herbs | 384 mg feverfew leaves | $10.79/ 100 capsules |
| The Vitamin Shoppe | 250 mg feverfew leaf extract standardized to 0.7% parthenolide | $9.95/ 60 capsules |
| Cardiovascular Research Ltd. | 125 mg specially prepared fraction of feverfew | $7.95/ 60 capsules |
| Natrol | 380 mg powdered feverfew | $5.50/ 90 capsules |
|
Source: Online mail-order firms __________________________________________________________________________________ |
||
Adverse Effects
Occasional mouth ulcerations have been reported with the use of fresh leaves, but have not been reported with the use of dried leaves in capsules. When asked specifically about mouth ulcerations, those in the Murphy et al treatment group reported this effect less often than the placebo group.9 Other reported adverse effects include contact dermatitis,10,11 palpitations, indigestion, colicky abdominal pain, weight gain, and inflammation of the lips, mouth, and tongue. Adverse effects reported at or below the frequency of placebo include dizziness, light-headedness, slightly heavier periods, heartburn, skin rash, and diarrhea.8,9
Abrupt discontinuation of feverfew after several years of use has led to the recurrence of incapacitating migraine.8 Feverfew is reputed to be an abortifacient and is documented to modify menstrual flow, cause abortion in cattle, and induce uterine contraction in a pregnant woman at term.12
Contraindications
Feverfew is contraindicated in individuals with known hypersensitivity to other members of the Asteraceae family, such as chamomile, ragweed, and yarrow. Feverfew is contraindicated during pregnancy. There is no information on feverfew excretion in breast milk.
Herb-Drug Interaction
Feverfew has been reported to inhibit platelet aggregation and increase fibrinolytic activity. Therefore, it is prudent for patients on anticoagulant and antiplatelet agents to avoid this herb until safety studies are available.
Recommendation
Evidence from two limited clinical trials suggests that feverfew, taken daily from three to eight months, can be effectively and safely used in migraine prophylaxis. As there is no comparison to traditional medications for migraine prophylaxis, no conclusion can be drawn for relative effectiveness. Feverfew is contraindicated in pregnancy and in patients with known hypersensitivity to related plants. Patients on antithrombotic and antiplatelet agents should also avoid feverfew. There are no data for use in children.
Dr. Goldberg is Coordinator of Complementary Medicine at The Permanente Medical Group in Oakland, CA.
References
1. Grieve M. A Modern Herbal. New York, NY: Dover; 1931:309-310.
2. Culpeper N. Culpeper’s Complete Herbal. London: Foulsham;139-141.
3. Hutchens AR. Indian Herbology of North America. Ontario: Merco; 1973:125-126.
4. An herbal encyclopedia. In: Hylton WH, ed. Rodale Herb Book. Emmaus, PA: Rodale Press; 1974:440-444.
5. Awang D. Prescribing therapeutic feverfew. Intern Med 1998;1:11-13.
6. DerMarderosian A. Feverfew. In: The Review of Natural Products, Facts and Comparisons. 1994.
7. Feverfew. Botanical Monograph Series. USP; 1997.
8. Johnson ES, et al. Efficacy of feverfew as prophylactic treatment of migraine, Br Med J 1985;291:569-573.
9. Murphy JJ, et al. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988;2:189-192.
10. Guin JD, Skidmore G. Compositae dermatitis in childhood. Arch Dermatol 1987;123:500-502.
11. Hausen BM, Osmundsen PE. Contact allergy to parthenolide in Tanacetum parthenium (L.) Schula-Bip. (feverfew, Asteraceae) and cross-reactions to related sesquiterpene lactone containing Compositae species. Acta Derm Venereol (Stockh)1983;63:308-314.
12. Newall CA, et al. Feverfew in Herbal Medicines. London: The Pharmaceutical Press; 1996:119-121.
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