In a joint report published in April 2012 by the American Academy of Neurology (AAN) and the American Headache Society (AHS), researchers concluded that a proprietary extract of butterbur (Petasites hybridis, Asteraceae) root is effective in reducing the frequency of episodic migraines.¹ The finding, published in the journal Neurology, was part of the organizations’ updated evidence-based treatment guidelines, which specifically examined the efficacy of what they term “complementary treatments” and non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen.

“Non-prescriptive treatments are important for many patients,” said Frederick Freitag, MD, a co-author of the new guidelines and medical director of The Headache Center of Baylor Health Care System in Dallas, Texas (email, July 25, 2012). “As with any treatment for migraine, appropriate discussion with the patient’s clinician regarding choices and subsequent monitoring for safety and efficacy can be very beneficial.”

To assess the effectiveness of non-prescription treatments, a panel of headache and methodology experts conducted a literature review of migraine prevention studies from June 1999 through May 2007. Treatments were considered to have established efficacy if two or more supporting Class 1 human clinical trials existed in the literature. According to its website, Neurology defines a Class 1 trial as a “randomized, controlled clinical trial of the intervention of interest with masked or objective outcome assessment, in a representative population.”²

Only 2 studies of butterbur extracts for migraine prevention met the criteria for inclusion, each of which compared placebo treatment to various dosages of the butterbur root extract supplement Petadolex^®(Linpharma Inc., Orlando, FL; manufactured in Germany by Weber & Weber), which has been commercially available in Europe for more than 25 years. It has been available in the United States as a dietary supplement since 1999 (V. Gallichio, email, August 14, 2012).

Both studies concluded that certain doses of Petadolex were significantly more effective than placebo. “Petadolex brand of butterbur root is a reasonable alternative to prescriptive medication and when properly prescribed and monitored can be a very effective and safe preventative treatment for migraine,” said Dr. Freitag.

Although this is not the first case of an American medical organization recommending a specific herbal treatment option for an illness or disorder, it does not happen frequently due to the amount and type of research required for such recommendations. In its clinical practice guidelines, the American Urological Association notes positive outcomes of studies using saw palmetto (Serenoa repens, Arecaceae) berry extract and stinging nettle (Urtica dioica, Urticaceae) for the treatment of benign prostatic hyperplasia (BPH), but it does not offer an endorsement of these herbal options, describing the quality, size, and length of available studies as “suboptimal.”³ Saw palmetto, however, is described as a secondary recommended treatment (“Grade B”) for patients with BPH by the American Association of Clinical Endocrinologists in their medical guidelines for the clinical use of dietary supplements and nutraceuticals.⁴

In its 2009 review of evidence-based clinical practice guidelines, the Society for Integrative Oncology explains why complementary therapies, including herbal medicine, are often not formally recommended by medical organizations, despite promising research. “A gap exists between the current level of scientific evidence and what we need to know to provide evidence-based advice, but rigorous scientific research is ongoing,” the authors wrote in the report.5 “A demonstrably favorable risk/benefit profile is essential for the use of complementary therapies, as it is for any form of medicine. The advantages of a rigid, evidence-based approach based on reductionism, however, do not translate easily into the holistic approach required for complex health issues.”

The National Center for Complementary and Alternative Medicine (NCCAM) has compiled a list of clinical practice guidelines from a variety of medical organizations on its website, which includes botanicals with varying levels of supporting evidence. The list is available at http://nccam.nih.gov/health/providers/clinicalpractice.htm.

In their 2001 paper in Alternative Medicine Review — one of the studies included in the recent migraine prevention literature review — researchers Werner Grossman and Hanns Schmidramsl explained Petadolex’s presumed mechanism of action.⁶ “Petadolex is an extract of the rhizome from Petasites hybridus, and petasine and isopetasine are the main components,” they wrote. “It has been shown that petasine and isopetasine are strong vasodilatory substances, whereby this effect on smooth muscle preparations in vitro is equivalent to papaverine.” (Papaverine is a medication prescribed for migraines in adults and children, derived from the opium poppy [Papaver somniferum, Papaveraceae].)

The etiology of migraines, which are 3 times more common in women, is still contested. Once thought to be primarily related to cranial vasculature, new theories — including genetic predisposition, hyperexcitable neurons (particularly the trigeminal nerve), and inflammation — have emerged in recent years.⁷

In addition to its use for migraine prevention, butterbur root has been used traditionally for pain management, anxiety, fever, and gastrointestinal conditions. In its “Herbs at a Glance” factsheet published in March 2012, NCCAM noted the well-known fact that the butterbur plant contains chemicals known as pyrrolizidine alkaloids (PAs), which have been shown to cause liver damage.8 NCCAM cautions consumers to use only butterbur products labeled as PA-free. European regulatory agencies allow butterbur root and aerial parts preparations to be marketed only if the daily dosages stay within a very low prescribed maximum level of PAs. For example, the German Commission E monograph (under the common name Petasites Root in the English translation) states that the daily dose of butterbur root preparations must not exceed 1 mcg of PAs.⁹

Accordingly, Petadolex supplements are processed in a manner that reduces PAs to undetectable levels. As stated on the company’s website, “Petadolex is manufactured by a patented method for extracting the beneficial liquid of the butterbur plant without the PAs. This purification process guarantees that Petadolex is free of detectable PAs.”¹⁰

In addition to butterbur root extracts, experts involved in the recent Neurology report reviewed studies on antihistamines, Co-Q10, estrogen, hyperbaric oxygen, magnesium, and MIG-99, a supercritical carbon dioxide-extract of the herb feverfew (Tanacetum parthenium, Asteraceae) that is no longer being manufactured (V. Gallichio, email, August 14, 2012).1 A single Class 1 study and 2 Class 2 studies on MIG-99 and migraine prevention were available in the time period reviewed by the authors, which was enough evidence to label feverfew extract a “Level B” treatment (medications that are “probably effective”).

While Petadolex has been shown to be effective in reducing episodic migraines, more research is needed on other formulations of butterbur, as well as other herbs that may offer relief to migraine sufferers. Revised guidelines for acute migraine treatment, separate from preventative treatment, are currently in development.

—Tyler Smith

References

1. Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012:78;1346-1353. Available at: www.neurology.org/content/78/17/1346.full. Accessed August 3, 2012.
2. Levels of evidence. Neurology website. Available at: . Accessed August 3, 2012.
3. Results of the treatment outcomes analyses. American Urological Association Education and Research, Inc. website. Available at: www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines/main-reports/bph-management/chap_3_ResultsTreatment OutcomesAnalyses.pdf. Accessed September 17, 2012.
4. Brett EM, Chausmer AB, Dickey RA, Wallach S. American Association of Clinical Endocrinologists: medical guidelines for the clinical use of dietary supplements and nutraceuticals. Endocrine Practice. 2003;9(5):430. Available at: www.aace.com/files/nutraceuticals-2003.pdf. Accessed September 17, 2012.
5. Deng GE, Frenkel M, Cohen L, et al. Evidence-based clinical practice guidelines for integrative oncology: complementary therapies and botanicals. Journal of the Society for Integrative Oncology. 2009;7(3):87. Available at: www.integrativeonc.org/index.php?option=com_rubberdoc&view=doc&id=39&format=raw. Accessed September 17, 2012.
6. Grossmann W, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Alt Med Rev. 2001;6(3):303-310. Available at: www.thorne.com/media/alternative_ medicine_review/2001/Volume_6/Number_3/Petasites_Migraine.pdf. Accessed August 3, 2012.
7. Evans RW, Evans ER. Expert opinion: what causes migraine: which physician explanation do patients prefer and understand? Headache. 2009;49:1536-1540. Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2009.01562.x/abstract. Accessed August 3, 2012.
8. Butterbur. Herbs at a Glance. The National Center for Complementary and Alternative Medicine website. Available at: http://ncaam.nih.gov/health/butterbur. Accessed August 3, 2012.
9. Blumenthal M, Busse WR, Goldberg A, et al. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston, MA: Integrative Medicine Communications; 1998.
10. FAQs. Petadolex website. Available at: www.petadolex.com/Faqs.aspx. Accessed August 7, 2012.