Reviewed: Lipton R, Govel H, Einhaupl K. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
Reviewed: Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache. 2005;45:1-8.
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 article reviews two recently published studies that investigated the efficacy of a special extract of butterbur root (Petasites hybridus [L.] P. Gaertn., B. Mey. & Scherb., Asteraceae) in the prevention of migraine headaches. Both studies employed the same standardized butterbur root extract, PetadolexA8 [Weber & Weber GmbH & Co. KG, Germany]. The first study demonstrated efficacy in treating adults while the second was effective in treating children and adolescents.
Butterbur for Migraines in Adults
This randomized, double-blind, three-arm, parallel-group, placebo-controlled trial investigated the efficacy of butterbur root extract (Petadolex) 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 (active sesquiterpenes) and contains no detectable levels of hepatotoxic pyrrolizidine alkaloids (PAs, normally found in butterbur root and leaf), per German pharmaceutical requirements. Petadolex contains less than 0.01 ppm (parts per million) PAs, according to the manufacturer.
The trial was conducted at several medical centers, the primary ones being the Department of Neurology and Epidemiology and Population Health at the Albert Einstein College of Medicine in Bronx, New York, and the New York Headache Center in New York City, as well as another center in the United States and 2 in Germany. 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 2 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.
Butterbur for Migraines in Children and Adolescents
Migraines occur in an estimated 3% to 7% of all children. Because most migraine therapies seem to be ineffective in children, there is a strong need for further research on migraine prevention in children. Numerous studies have evaluated therapies for adults with migraines; however, only a few controlled trials have investigated the prophylactic treatment of migraines in either children or adolescents.
The purpose of this open-label study was to determine the safety and efficacy of a standardized butterbur extract in the prevention of migraines in children and adolescents.
The study was open-label because approval of placebo-controlled trials in children is difficult to obtain from an ethical review board in Germany.
A total of 108 children (n = 29 [6-9 years]) and adolescents (n = 79 [10-17 years]) were enrolled in this multicenter prospective, open-label study in German medical practices. Only patients suffering from migraines for at least 1 year were included in the trial. Patients were treated with 50 to 150 mg of the special butterbur root extract (Petadolex) for 4 months. The dose of the butterbur was dependent on the subjects’ age and tolerance of the medication. Treatment progression was recorded in migraine journals especially designed for children and adolescents.
The number of migraine attacks in children and adolescents were substantially reduced by the butterbur root extract. Of all patients, 77% reported a reduction in the frequency of migraine attacks by at least half. Ninety-one percent of patients reportedly felt substantially or at least slightly improved after 4 months of butterbur treatment. The butterbur extract was very well tolerated with few adverse events. As with the trial on adults summarized above, burping was the most commonly reported adverse effect and is the only significant and well-known side effect of the standardized butterbur extract. All other adverse events were mild and did not lead to premature termination of the study.
The results of this study indicated that butterbur root extract may be an effective and well-tolerated prophylactic treatment of migraines in children and adolescents. Furthermore, the data reported here confirm the results found in previous clinical studies and drug-monitoring trials in adults. The authors caution that although the uncontrolled design of this study alone was not sufficient to draw any definite conclusions regarding effectiveness of butterbur, these results together with the available data from randomized trials demonstrate that Petadolex seems to be an effective alternative for prophylactic migraine treatment in children and adolescents. They suggested that the results warrant a placebo-controlled trial in children and adolescents to further document butterbur’s efficacy in migraine prevention of this patient group. Overall, the results of this study with a natural product are promising for young patients affected by migraines.
—John Neustadt, ND, Heather S. Oliff, PhD, and Mark Blumenthal
1. Kelman L. The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. Headache. 2004 October;44(9):865-872.>