"Natural" or Alternative Medications for Migraine Prevention

Randolph W. Evans, MD; Frederick R. Taylor, MD


Headache. 2006;46(6):1012-1018. 

In This Article


Petasites hybridus, known commonly as butterbur, is a perennial shrub which grows wild on German riverbanks. Nonextracted plant parts are carcinogenic, hepatotoxic, lung toxic, and may cause coagulopathy. The German Health Authority (Commission E) certifies the brand name Petadolex from Weber and Weber GmbH & Co as nontoxic. Petadolex is a patented, standardized CO2 rhizome root extraction of Petasites marketed in Europe since 1992. Petadolex very recently has been marketed as a component in at least 1 combination product, which also contains several other ingredients discussed in this article. Despite a recent positive trial published in Neurology, due to the limited total number of subjects studied, neither the long-term safety nor the efficacy of Petadolex can be considered unequivocally established (Grade B evidence).

The 2 RCTs investigating Petadolex represent a thin evidence base. In the smaller study, 60 subjects were treated with placebo or Petadolex 100 mg per day for 12 weeks.[21,22] According to investigators, "the frequency of migraine attacks decreased by a maximum of 60% compared to the baseline… .and was significant (P< .05) compared to placebo." Due to major shortcomings of the original analysis and to comply with regulatory requirements, the data were independently reanalyzed.[23] In this reanalysis, the responder rate (≥50% reduction in migraine frequency) was 45% in the Petadolex group and 15% in the placebo group. In a study of 245 subjects, Lipton et al reported decreased monthly migraine frequency after 4 months and a detectable treatment effect at 1 month; a double-blind, placebo-controlled 3-arm, parallel-group dose-ranging design was used.[24] The migraine attack frequency in the Petasites (Petadolex) 75 mg bid cohort was reduced 48% versus 26% for placebo; 68% of the Petadolex subjects had ≥50% reduction in migraine frequency compared with 49% of those on placebo. Petadolex 50 mg bid was not found to be statistically superior to placebo. The TG for ≥50% reduction in migraine frequency for the 150 mg Petadolex was 19%. Studies of amitriptyline, propranolol, and timolol (the latter 2, FDA approved for migraine prophylaxis) have revealed TGs of 21%, 24%, and 20%, respectively, for ≥50% reduction in headache attacks, albeit using less rigorous methodology and analyses.[25,26]

The Petadolex RCT adverse event profile compared favorably with placebo except for excess eructions (burping) in both active treatment arms. Long-term safety data are limited, as the average duration of use is estimated to be 3 months; shorter term safety appears to have been adequately evaluated, with an estimated more than 450,000 patients treated and >75,000 patient years of exposure as of 2003.[27] Although some concerns remain, it would seem fair to state that Petadolex may be the best safety tested herbal to date for the treatment of headache with CAM.[28,29] It should be noted, however, that due to lack of data, such affirmation for other Petasites preparations currently must be withheld.


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