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|Date: March 15, 2005||HC# 020251-276|
Re: Standardized Extract of Butterbur Root (Petadolex) Prevents Migraines in Multi-center Clinical Trial
Lipton R, Govel H, Einhaupl K. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
Migraine headaches vary in intensity and duration. Many migraine sufferers describe a debilitating pain made worse with light, sound, and movement, and some experience nausea and vomiting. Basically, there are two types of migraines: those with and without aura. Aura is defined as symptoms of the nervous system (usually visual) that precede a migraine and are usually followed by the headache within one hour. These symptoms may include visual disturbances such as flashing lights, bright spots, blurry vision, or blind spots. Aura may also involve auditory, sensory, or motor symptoms. Headache normally follows aura symptoms either directly or within one hour. A warning sign that occurs much more frequently is the "prodrome phase." Prodrome is experienced by approximately 30% of people with migraines,1 and it occurs within hours or up to days before a migraine attack. Many physical and psychological symptoms are associated with prodrome. These symptoms may vary among migraine sufferers but they usually remain consistent for a particular individual. A migraine sufferer may experience changes in mood, behavior, energy level, and appetite.
This randomized, double-blind, three-arm, parallel-group, placebo-controlled trial investigated the efficacy of butterbur (Petasites hybridus (L.); Asteraceae) root extract (Petadolex®, Weber and Weber GmbH & Co. KG, Germany) for the prevention of migraine headaches. Petadolex is a special extract of butterbur root that is standardized to contain at least 15% petasin and isopetasin and contains no detectable levels of hepatotoxic pyrrolizidine alkaloids (PAs). It is important that only butterbur extracts with the Pas removed be ingested, since the Pas in butterbur are toxic to the liver. Petadolex contains les than 0.01 ppm PAs.
The trial lasted 20 weeks, with an initial 4-week baseline phase followed by a 16-week treatment phase. Researchers initially enrolled 245 migraine patients in the run-in phase; 229 patients (ages 18-65 years, mean age 42 years) with a history of 2 to 6 migraine headaches per month in the 3 months prior to treatment, and at least 2 headaches during the 4-week baseline phase were randomized to each of the 3 treatment arms. Excluded from the trial were people with nonmigraine headaches lasting greater than 6 days per month in the 3 months prior to the study, people who had received prophylactic migraine treatment in the 3 months prior to the study, women who were at risk of getting pregnant, and women who were breastfeeding. Patients in the two treatment arms received either a 50 mg or 75 mg Petadolex tablet twice a day; patients in the third arm received a matching placebo.
The primary outcome measure was the change in the frequency of migraine attacks over the 4-month treatment period. Secondary endpoints included the reduction in migraine attack frequency per month; number of therapy responders (reduction of at least 50% in attack frequency compared to baseline); patient use of rescue medications; adverse events; and laboratory measures of safety, including bilirubin and the liver enzymes SGOT (serum glutamic-oxaloacetic transaminase), SGPT (serum glutamic-pyruvic transaminase), and GGT (gamma glutamyl transpeptidase).
Overall, 202 patients completed the clinical trial according to the study protocol. Supplementation with 150 mg/day of Petadolex significantly reduced the average number of monthly migraines compared to placebo (–45% in the 150 mg/day treatment group vs. –28% in the placebo group, p = 0.005). Patients taking 100 mg/day had a non-significant 32% decrease in number of attacks compared to placebo (p = 0.43). Those taking 150 mg of butterbur had a significantly greater reduction in migraine occurrence compared to those taking 100 mg of butterbur (–45% vs. –32%, p = 0.04). Frequency of migraines was significantly reduced compared to baseline in the 150 mg group compared to placebo after 1, 3, and 4 months of treatment (–38% vs. –19% at one month, respectively [p = 0.02]; –58% vs. –26% after 3 months, respectively [p = 0.001]; –51% vs. –32% after 4 months, respectively [p = 0.02]). Although patients taking 100 mg had a 42% decrease in number of attacks per month at 3 months, the difference was statistically not significant compared to placebo.
No consistent pattern of treatment effect in any group on attack duration or intensity was detected. Treatment with 150 mg resulted in a greater than 50% reduction in migraines per month over baseline after 1, 2, 3, and 4 months in a significant percentage of patients compared to placebo (54% vs. 33% after 1 month, respectively; 60% vs .43% after 2 months, respectively; 71% vs. 52% after 3 months, respectively; 68% vs. 49% after 4 months, respectively; p < 0.05 at all time periods).
Adverse events were deemed to be mild or moderate. Frequency of adverse events was comparable in all groups; however, significantly more volunteers taking either 150 mg or 100 mg of butterbur experienced burping than in the placebo group (p value not reported).
This trial demonstrates the safety and efficacy of 150 mg/day of the Petadolex butterbur root extract in preventing migraine headaches. The authors note the efficacy attained with 150 mg/day butterbur is comparable to the observed benefits from prescription medications (e.g., propranolol, metoprolol, flunarizine, valproic acid, topiramate and gabapentin), while the safety of butterbur appears superior to these drugs.
—John Neustadt, ND4
1Kelman L. The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. Headache. 2004 Oct;44(9):865-872.