Petasites (Butterbur) in Pediatric Migraine Management

Migraines in pediatric populations present a significant challenge, both for families and healthcare providers. As the search for effective, safe, and well-tolerated preventive treatments continues, Petasites hybridus—commonly known as butterbur—has emerged as a compelling option. 

In this article, I’ll dive into the clinical application of butterbur for pediatric migraine management, exploring its traditional uses, phytochemistry, safety profile, clinical evidence, and considerations for integrative pediatric practice.

Traditional Uses of Butterbur in Medicine

The Petasites genus, part of the Asteraceae family, is a perennial plant known for its thick, creeping underground rhizomes and large, distinctive leaves. In the first century AD, the Greek physician Dioscorides described butterbur as “a shoot, taller than a cubit and thick as a thumb, bearing large, hat-shaped leaves, as if they were mushrooms, and [..] good for malignant and cancerous ulcers.” The genus name, Petasites, is derived from the Greek word petasos, meaning “rain hat.” The large leaves of the plant also lend to it’s common name as they were historically used to wrap butter during warm weather. Of the 19 widely recognized species in this genus, P. hybridus is the most extensively studied. In this discussion, “butterbur” will refer specifically to Petasites hybridus unless otherwise noted.^1,2

Butterbur has been utilized for centuries in traditional medicine across Europe and Asia, predominantly for its anti-inflammatory and antispasmodic properties. Traditionally, butterbur was employed to treat a variety of conditions such as headaches, hypertension, dysmenorrhea, allergic rhinitis, fever, gastrointestinal disturbances, and respiratory ailments, with a particular emphasis on relieving coughs and asthma. ^1,2

Modern research has shown benefit for the use of butterbur in allergic rhinitis, anxiety, depression and migraines. Evidence is mixed on its efficacy for allergic skin reactions, chronic obstructive bronchitis, insomnia, upset stomach, urinary tract symptoms, asthma, and other conditions.³ 

In the context of migraine, butterbur’s use can be traced back to its application in treating pain and reducing inflammation, key factors in migraine pathophysiology. Its long-standing history in herbal medicine, coupled with anecdotal reports of efficacy, laid the groundwork for modern investigations into its role in migraine prevention, including in pediatric populations.

Phytochemistry and Mechanisms of Action

The therapeutic potential of butterbur in migraine management is largely attributed to its active compounds, primarily sesquiterpene esters—namely petasin and isopetasin prepared from the rhizome and/or leaves of butterbur. These compounds are thought to exert several key effects that make butterbur particularly suitable for migraine prevention:

1. Inhibition of Inflammatory Mediators: Petasins inhibit the production of inflammatory mediators such as prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and cysteinyl-leukotrienes. This inhibition is achieved through the suppression of cyclooxygenase (COX-2), lipoxygenases, and phospholipase A2 activities, all of which are critical in the inflammatory cascade associated with migraine pathophysiology​.^3,4
2. Desensitization of Nociceptive Pathways: Butterbur’s efficacy in migraine management is partly due to its ability to desensitize nociceptive pathways by modulating TRP channels, specifically TRPA1 and TRPV1, which are critical in pain and neurogenic inflammation. Isopetasin, an active compound in butterbur, inhibits these channels, reducing calcium influx and the release of calcitonin gene-related peptide (CGRP), a key neuropeptide in migraine pathogenesis. Studies have shown that butterbur extracts significantly reduce CGRP release in response to TRPA1 and TRPV1 activation in both rodent and human models, highlighting its potential as a targeted natural therapy for migraines, particularly in patients seeking alternatives to conventional treatments.³
3. Calcium Channel Blocking: Petasins also exhibit calcium channel blocking activity, which is particularly relevant in the context of migraine. Voltage-gated calcium channels are essential in the transmission of nociceptive information, and by blocking these channels, petasins may reduce the transmission of pain signals, contributing to migraine prevention​.³
4. Neuroprotection and Antioxidant Effects: Butterbur contains antioxidant compounds that help mitigate oxidative stress, a contributing factor in migraine pathogenesis.These compounds inhibit key inflammatory pathways, such as NF-κB, reduce oxidative stress, and protect neurons from ischemic injury. Notably, petatewalide B activates the AMPK/Nrf2 signaling pathway, enhancing antioxidant defenses. Butterbur also contains potent antioxidants, including quercetin derivatives and caffeic acid, which help maintain cellular redox balance and reduce lipid peroxidation. These effects collectively contribute to butterbur’s potential in managing neurological conditions like migraines, particularly by mitigating oxidative and inflammatory damage.⁴

In addition to the above compounds, there are minor components including  essential oils, pyrrolizidine alkaloids (PAs), and isometric oxopestasan esters. 

Safety Profile: Considerations for Pediatric Use

The safety of butterbur, particularly in children, is a significant concern due to the presence of pyrrolizidine alkaloids (PAs) in the plant. These compounds, common in the Asteraceae, Boraginaceae, and Fabaceae families, serve as chemical defenses against herbivores but are known for their hepatotoxic, potentially carcinogenic, and lung-damaging effects. ^1,3 

Although reports of hepatotoxicity linked to butterbur are rare, they must be carefully considered, especially with long-term use. One serious concern is the association with reversible cholestatic hepatitis, which led the American Academy of Neurology to stop recommending butterbur for migraine management in 2015. In animal studies, rats exposed to doses 15 times higher than the maximum clinical dose (MCD) of 3 mg/kg/day did not show observable adverse effects. However, at doses 45 to 90 times higher, researchers noted bile duct hyperplasia, likely due to changes in transport proteins. Importantly, studies on human liver cells have not demonstrated liver toxicity at therapeutic levels of butterbur, even when combined with typical migraine medications.^1–4 

To mitigate these risks, commercial butterbur preparations like Petadolex® undergo rigorous processing to remove harmful pyrrolizidine alkaloids, significantly reducing the potential for toxicity. In clinical trials, Petadolex® has shown no reports of abnormal liver function and remains the only butterbur extract extensively evaluated for safety and efficacy in migraine prophylaxis. ^1–4 

Despite the concerns surrounding safety, butterbur remains a promising option for migraine prevention when used correctly. Its strong scientific backing has led to its inclusion in several guidelines, and with proper precautions, its benefits can outweigh the risks. In 2008, the German Migraine and Headache Society and the German Neurological Society recommended Petasites extract (Petadolex®, 75 mg twice daily) as a second-line treatment for migraine prophylaxis, while advising about potential side effects like eructation, stomach pain, and liver dysfunction. The Canadian Headache Society also strongly endorsed butterbur for migraine prevention. Although the American Academy of Neurology initially recognized butterbur as a level A treatment in 2012, concerns about PA toxicity later prompted them to withdraw this recommendation in 2015. Nevertheless, all guidelines stress the importance of using only PA-free products with standardized petasin content. Additionally, it’s important to consider that individuals with allergies to ragweed, daisies, or related plants may have an increased risk of allergic reactions to butterbur.¹

Evidence Supporting Butterbur in Pediatric Migraine Management

Clinical evidence supporting the use of butterbur for pediatric migraine prevention is compelling.

• Oelkers-Ax et al. (2008): In this randomized controlled trial (RCT), elementary school-aged children received butterbur extract, and/or music therapy or placebo for a period of 28 weeks. The trial demonstrated that butterbur, at both low (50 mg) and high (150 mg) doses, significantly reduced the frequency of migraine attacks compared to placebo, with a responder rate of 77% in the experimental group versus 31% in the control group​.⁵
• Lipton et al. (2004): This randomized, double-blind, placebo-controlled trial examined the efficacy of Petadolex® in patients with episodic migraine. The study found that patients receiving 150 mg daily of Petadolex® experienced a 48% reduction in migraine attack frequency, significantly greater than the 36% reduction in the 100 mg group and the 26% reduction in the placebo group. Additionally, 68% of patients in the 150 mg group achieved a >50% reduction in attack frequency after four months, compared to 56% in the 100 mg group and 49% in the placebo group, underscoring the efficacy of higher doses of Petadolex® in migraine prevention​.⁶
• Grossman et al. (2001): In this randomized, group-parallel, placebo-controlled, double-blind trial, adult patients were administered 25 mg of Petadolex® twice daily over 12 weeks. The study reported a high efficacy and tolerance for the treatment, with a significant reduction in the number of migraine attacks per 4-week period. The >50% responder rate was notably higher in the Petadolex® group (45%) compared to the placebo group (15%).⁷

These studies provide robust evidence for the efficacy of butterbur, particularly Petadolex®, in reducing migraine frequency and severity in both pediatric and adult populations. The data suggests that butterbur may be a viable option for patients, especially those who have not responded well to other preventive treatments or who seek alternative therapies. 

Clinical Considerations for Integrative Pediatric Practice

When integrating butterbur into a pediatric migraine management plan, clinicians must consider several factors:

1. Risk-Benefit Assessment: Evaluate the individual patient’s migraine severity, frequency, and response to other treatments. Butterbur may be particularly beneficial for children who have not responded well to conventional pharmacotherapy, who experience significant side effects from other migraine preventives, or whose families prefer non-pharmacologic approaches to management. 
2. Integrative Approach: Butterbur should be used as part of a comprehensive migraine management plan that includes lifestyle modifications, dietary adjustments, stress management, and, where appropriate, other natural therapies. For instance, combining butterbur with magnesium supplementation or cognitive behavioral therapy (CBT) may enhance overall treatment outcomes.
3. Dosing and Monitoring: The recommended dosing for pediatric patients typically ranges between 50 mg to 150 mg per day, depending on the preparation and the patient’s weight. Regular monitoring of liver function tests (LFTs) is advised, especially during long-term therapy, to detect any potential hepatic adverse effects early.
4. Adverse Effects: While generally well-tolerated, butterbur may cause gastrointestinal disturbances, belching, headaches, and drowsiness. Clinicians should educate parents about these potential side effects and encourage prompt reporting of any unusual symptoms.
5. Informed Consent: It is crucial to discuss the potential risks and benefits of butterbur with the child’s parents or guardians. This includes explaining the importance of using PA-free products, the need for regular liver function monitoring, and the potential for allergic reactions.

Closing Thoughts & Clinical Perspectives:

Butterbur offers a promising option for the preventive management of pediatric migraines, with clinical trials suggesting its potential to reduce migraine frequency and severity in children. However, due to concerns about pyrrolizidine alkaloid (PA) contamination and possible hepatotoxicity, careful consideration is needed when recommending butterbur. 

In my clinical practice, I consider butterbur a secondary option for pediatric migraine management, not so much due to safety concerns—since there are PA-free sources available—but primarily because of the lack of robust evidence supporting its use. The research available is limited, with few trials conducted and small populations studied, which leaves me hesitant to prioritize butterbur over other treatments. Instead, I focus on identifying and addressing migraine triggers, implementing lifestyle modifications like increasing dietary omega-3s, and correcting common nutrient deficiencies such as low vitamin D and magnesium. ^8–14

If you’re curious to explore more about integrative approaches to migraine management, I invite you to join my upcoming webinar on Nat Peds Pro. In this session, I’ll dive deeper into evidence-based strategies, including natural therapies, lifestyle modifications, and personalized treatment plans to help you better manage migraines in pediatric patients. Don’t miss this opportunity to enhance your practice with practical insights and clinical expertise.

References

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2. Butterbur. NCCIH. Accessed August 20, 2024. https://www.nccih.nih.gov/health/butterbur

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7. Grossman W, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Altern Med Rev J Clin Ther. 2001;6(3):303-310.

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9. Kılıç B, Kılıç M. Evaluation of Vitamin D Levels and Response to Therapy of Childhood Migraine. Med Kaunas Lith. 2019;55(7):321. doi:10.3390/medicina55070321

10. Cayir A, Turan MI, Tan H. Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients. Braz J Med Biol Res Rev Bras Pesqui Medicas E Biol. 2014;47(4):349-354. doi:10.1590/1414-431×20143606

11. Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm. 2012;119(5):575-579. doi:10.1007/s00702-012-0790-2

12. Rybicka  marta, Baranowska-Bosiacka I. The Role of Magnesium in Migraine Pathogenesis. Potential Use of Magnesium Compounds in Prevention and Treatment of Migraine Headaches. J Elem. Published online 2012. doi:10.5601/jelem.2012.17.2.15

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14. Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ. Oral Magnesium Oxide Prophylaxis of Frequent Migrainous Headache in Children: A Randomized, Double-Blind, Placebo-Controlled Trial. Headache J Head Face Pain. 2003;43(6):601-610. doi:10.1046/j.1526-4610.2003.03102.x