Standardized butterbur extract Petadolex®—herbal approach to migraine prophylaxis

Townsend Letter for Doctors and Patients, Oct, 2002 by Donald J. Brown

The development of a standardized extract of the rhizome of butterbur (Petasites hybridus) has led to a new clinical approach to the management of migraine headache. Two clinical trials with a standardized CO2 extract (Petadolex[R], Weber & Weber International GmbH & Co., Germany) have successfully demonstrated the extractis ability to safely and effectively reduce the frequency and intensity of migraine headaches.

Petasites hybridus is a perennial shrub native to Europe, northern Africa, and southwestern Asia that grows to about 3 feet tall. (1) Although butterbur is frequently used as the common name, the species is also commonly known as purple butterbur and also sweet coltsfoot. (2) A related plant, Petasites frigidus (L.) Fries, is known commonly as Arctic butterbur and less commonly Arctic sweet coltsfoot or western coltsfoot.

While the leaves and rhizome have been used in traditional herbal medicine, only medicinal preparations of the rhizome are approved by the German Commission E for use in modern phytotherapy. (3)

Active Constituents and Mechanism of Action

The leaves, rhizome, and roots of butterbur contain a mixture of eremophilan-type sesquiterpenes consisting primarily of petasin and isopetasin. (4) According to phytotherapy textbooks, petasin and isopetasin have both spasmolytic and analgesic actions. (5) These active constituents also inhibit leukotriene synthesis, which may also contribute to butterburis antispasmodic and anti-inflammatory actions. (6)

Butterbur leaf and rhizome also contain pyrrolizidine alkaloids (PAs), which are potentially hepatotoxic and carcinogenic constituents. (7) These potentially hepatotoxic and carcinogenic constituents have led to the demise of coltsfoot and comfrey root in herbal medicine and may be the primary explanation for the waning interest in the therapeutic use of butterbur in traditional herbal medicine. It is imperative that health care professionals recommend only butterbur products that are free of PAs.

Antispasmodic actions have led to the use of butterbur for urinary tract spasms due to kidney stones, digestive tract spasms, as well as low back pain. (8) It has also been used for whooping cough and bronchial asthma. A recent clinical trial found that a PA-free extract of the leaves (standardized to petasine content) was as effective as the antihistamine cetirizine in the treatment of allergic rhinitis. (9)

Clinical Use for Migraine Prophylaxis

Two randomized, placebocontrolled, double-blind clinical trials have tested the efficacy of the standardized butterbur extract Petadolex[R] in the treatment of migraines. In the first trial, 60 migraine patients (mean age 28.7 years) were randomized to receive either 50 mg of Petadolex or placebo b.i.d. for 12 weeks. (10) Starting at the 4th week of treatment, the Petadolex group had a significant reduction in the number of migraine attacks compared to the placebo group (p < 0.05). Compared to the placebo group, those taking Petadolex had a 60% reduction in the number of migraines by week 12. The number of migraine days was also reduced significantly in the Petadolex group (3.4 [ or -] 1.6 at baseline to 1.7 [ or -] 0.9 days after 12 weeks) compared to placebo (3.0 [ or -] 1.3 to 2.6 [ or -] 1.2 days, p < 0.05). While the duration and intensity of migraines was significantly reduced at 8 weeks in the Petadolex group (p < 0.05), the difference compared to placebo was not significant at week 12. The mean nu mber of accompanying symptoms (e.g. nausea, vomiting) was significantly reduced in the Petadolex group compared to placebo (p < 0.01). No adverse events were reported.

The second trial randomized 233 migraine patients (ages 19 to 65 years) to receive either 50 mg of Petadolex, 75 mg of Petadolex, or placebo b.i.d. for 16 weeks following a 4-week baseline run-in period. (11) The primary endpoint, frequency of migraine attacks per 4 weeks, was reduced by 38%, 44%, 58%, and 51% in patients treated with Petadolex 75 mg b.i.d. after 1 (baseline), 2, 3, and 4 months respectively. The 50 mg b.i.d. group had a reduction of 24%, 37% 42%, and 40%, while the placebo group was 19%, 26%, 26%, and 32%, respectively. Treatment differences between those taking Petadolex 50 mg b.i.d. were not significant compared to placebo. However, those taking 75 mg b.i.d. had a significant reduction in migraine count after 1, 3, and 4 months of treatment compared to placebo (p = 0.02, p = 0.001, p = 0.02, respectively). The number of patients who had a 50% reduction in mean attack frequency per month relative to baseline were considered therapy responders. The mean percent of responders in the 75 mg b.i .d. group was significantly greater than those taking placebo during the entire treatment with 71% responders after 3 months in the 75 mg b.i.d. group compared to 52% in the placebo-group (p = 0.03). The assessment of headache intensity after 3 months also favored the Petadolex 75 mg b.i.d. group compared to placebo (p = 0.02). The most frequently reported adverse events considered possibly related to treatment with Petadolex included mild gastrointestinal complaints.