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Petasites hybridus root (butterbur) is an effective preventive treatment for migraine
Abstract
To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine.
This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period.
Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping.
Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.
... An effective phytotherapeutical option in migraine prophylaxis is an extract from the rhizome of the plant butterbur (Petasites hybridus). Butterbur root extract with its active ingredients petasin and isopetasin (petasins) has been used in migraine prophylaxis for many years [20][21][22]. However, the site of action is still not clear. ...
... Its spasmolytic effects in the gastrointestinal [35] and the urinary tract [36], and anti-inflammatory activity in allergic rhinitis and asthma have been subjects of medical research [37][38][39]. A further therapeutic option for the use of the extract from the plant's rhizome is prophylactic migraine treatment [20][21][22]. ...
... However, this discrepancy might be again due to pretreatment with petasins. As mentioned above, butterbur root extract is successfully used in migraine prophylaxis [20][21][22]. However, long-term effects of either petasins in the extract or pure isopetasin could not be taken into consideration in this work. ...
Background
Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1.
Methods
We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay.
Results
Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels.
Conclusions
Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.
... An effective phytotherapeutical option in migraine prophylaxis is an extract from the rhizome of the plant butterbur (Petasites hybridus). Butterbur root extract with its active ingredients petasin and isopetasin (petasins) has been used in migraine prophylaxis for many years [20][21][22]. However, the site of action is still not clear. ...
... Its spasmolytic effects in the gastrointestinal [34] and the urinary tract [35], and anti-in ammatory activity in allergic rhinitis and asthma have been subjects of medical research [36][37][38]. A further therapeutic option for the use of the extract from the plant's rhizome is prophylactic migraine therapy [20][21][22]. ...
... As mentioned above, butterbur root extract is successfully used in migraine prophylaxis [20][21][22]. ...
Background: Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1.
Methods: We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay.
Results: Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels.
Conclusions: Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.
... Its clinical efficacy in migraine therapy was evidenced in placebo-controlled double-blinded clinical investigations. A significant reduction in the frequency of migraine attacks was reported [3,4] particularly after four months of treatment [5,6]. In 2012, the American Academy of Neurology concluded butterbur to be effective for migraine prevention [7]. ...
... Furthermore, Table 2 compiles 12 cases recorded during clinical trials. Patients provided informed consent prior to the study entry and details of the clinical trials are given in [3][4][5][6]. The HILI cases were evaluated according to the WHO-UMC system by an expert panel consisting of specialists in internal medicine/neurology, board certified pathologist and clinical pharmacologist and toxicologist. ...
... Unlike many HDS, it was extensively evaluated for safety and efficacy. In clinical studies, the spasmolytic properties and effectiveness in the prevention of migraine attacks was proven [5,6,21]. Therefore, butterbur extracts were recommended for migraine prevention [7]; however, reports of severe HILI cases (8 in Germany, 1 in UK and 1 in Austria) prompted concern regarding its safe use. ...
Petadolex®, a defined butterbur extract has clinically proven efficacy against migraine attacks. However, spontaneous reports indicate cases of herbal induced liver injury (HILI). While most HILI patients presented mild serum biochemistry changes (<3 ULN, dose range 50 to 225 mg/day; treatment duration 4–730 days) nine developed severe HILI (average time-to-onset 103 days, ALT-range 3–153; AST 2–104-fold ULN). HILI cases resolved after medication withdrawal though two patients required liver transplantation. Liver biopsies revealed an inconsistent injury pattern, i.e. necrosis, macrovesicular steatosis, inflammation, cholestasis, and bile duct proliferation. Causality assessment rated 3 cases likely, 13 possible, 8 unlikely and 24 as unclassifiable/unclassified. Note, 22 patients reported hepatotoxic co-medications especially during periods of pain. A no-observable-adverse-effect-level at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats. At >45 and 90-fold MCD bile duct hyperplasia was observed but could not be confirmed in an explorative minipig study at 218-fold MCD. Human hepatocyte studies at 49-fold Cmax serum petasins (=active ingredient) and therapeutic Ibuprofen, Paracetamol and Naratriptan concentrations evidenced liver transaminase and CYP-monooxygenase changes. Collectively, Petadolex® HILI cases are rare, idiosyncratic and frequently confounded by co-medications. A physician-supervised self-medication plan with herbs and pain relief medication is needed to minimize risk for HILI.
... It is reported to cause reversible fetal or neonatal bradycardia [79][80][81][82][83][84][85][86][87][88][89]. ...
... Herbal Options: Petasite extract 75 mg twice a day is a well-tolerated and effective herbal medication without apparent hepatotoxic side effects at this dose and is used for decreasing the frequency of migraine attacks. It is an effective option to be referred to in adults [79][80][81]. It is also well tolerated and effective in children and teenagers at lower doses [82]. ...
Migraine affects about one billion people worldwide yearly and is one of the most common neurologic illnesses, with a high prevalence and morbidity, particularly among young adults and females. Migraine is associated with many comorbidities, including stress, sleep difficulties, and suicidal ideation. Migraine, despite its widespread occurrence, is underdiagnosed and undertreated. Because of the complicated and primarily unknown mechanisms of migraine formation, several social and biological risk factors, such as hormone imbalances, genetic and epigenetic impacts, and cardiovascular, neurological, and autoimmune illnesses, have been proposed. Through the mid-20th century diversion of the now-defunct vascular theory, the pathophysiology of migraine has developed from a historical study of the "humours" to a distinct entity as a neurological disorder. The range of therapeutic targets has broadened significantly, increasing the number of specialized clinical trials. Understanding the biology of migraine through careful research has resulted in the identification of major therapeutic classes: (i) triptans, serotonin 5-HT1B/1D receptor agonists, (ii) gepants, calcitonin gene-related peptide (CGRP) receptor antagonists, (iii) ditans, 5-HT1F receptor agonists, (iv) CGRP monoclonal antibodies, and (v) glurants, mGlu5 modulators, with further targets being explored. This review provides a comprehensive overview of the most recent literature on epidemiology and risk factors and exposes knowledge gaps.
... The edible parts of P. japonicus (fukinoto) together with its rootstocks and leaves are used in the traditional Korean, Japanese and Chinese medicine (Choi et al., 2016). Nowadays, the most researched therapeutic effects of butterbur concern its anti-migraine and anti-allergic properties (Lipton et al., 2004;Oelkers-Ax et al., 2008;Pothmann and Danesch, 2005). ...
... In a later study, 202 patients with migraine were randomized into three groups: two receiving Petadolex® (50 mg and 75 mg butterbur extracts, respectively) and one placebo group. The trial showed that only the dose of 75 mg was significantly more effective than placebo and decreased the migraine attack frequency over 4 months of treatment (Lipton et al., 2004). A multicenter, prospective, open-label clinical study proved the potential of P. hybridus in the migraine prophylaxis for children and teenagers; 108 patients with ages between 6 and 17 were treated with Petadolex® (50-150 mg extract daily, depending on age) over 4 months; the results showed a reduction in the frequency of migraine attacks (Pothmann and Danesch, 2005). ...
Ethnopharmacological relevance
Petasites (butterbur, Asteraceae) species have been used since Ancient times in the traditional medicine of Asian and European countries to treat central nervous system (migraine), respiratory (asthma, allergic rhinitis, bronchitis, spastic cough), cardiovascular (hypertension), gastrointestinal (ulcers) and genitourinary (dysmenorrhea) disorders.
Aim of the review
This study summarized and discussed the traditional uses, phytochemical, pharmacological and toxicological aspects of Petasites genus.
Materials and methods
A systematic search of Petasites in online databases (Scopus, PubMed, ScienceDirect, Google Scholar) was performed, with the aim to find the phytochemical, toxicological and bioactivity studies. The Global Biodiversity Information Facility, Plants of the World Online, World Flora Online and The Plant List databases were used to describe the taxonomy and geographical distribution.
Results
The detailed phytochemistry of the potentially active compounds of Petasites genus (e.g. sesquiterpenes, pyrrolizidine alkaloids, polyphenols and essential oils components) was presented. The bioactivity studies (cell-free, cell-based, animal, and clinical) including the traditional uses of Petasites (e.g. anti-spasmolytic, hypotensive, anti-asthmatic activities) were addressed and followed by discussion of the main pharmacokinetical and toxicological issues related to the administration of butterbur-based formulations.
Conclusions
This review provides a complete overview of the Petasites geographical distribution, traditional use, phytochemistry, bioactivity, and toxicity. More than 200 different sesquiterpenes (eremophilanes, furanoeremophilanes, bakkenolides), 50 phenolic compounds (phenolic acids, flavonoids, lignans) and volatile compounds (monoterpenes, sesquiterpenes) have been reported within the genus. Considering the phytochemical complexity and the polypharmacological potential, there is a growing research interest to extend the current therapeutical applications of Petasites preparations (anti-migraine, anti-allergic) to other human ailments, such as central nervous system, cardiovascular, malignant or microbial diseases. This research pathway is extremely important, especially in the recent context of the pandemic situation, when there is an imperious need for novel drug candidates.
... In a 16-week trial, conducted by Lipton and colleagues [80], three groups of treatment were compared: Butterbur 50 mg twice daily, Butterbur 75 mg twice daily, and placebo. The 75 mg Butterbur group reported a significant reduction in migraine attacks per months (−45%), while the other two groups reported a minor decrease in the number of migraine attacks per month (−32% for the 50mg Butterbur group and -28% for the placebo group). ...
... Behavioral approaches have an important role in reducing headache frequency and in producing improvements in other patient-reported outcomes that significantly contribute to the prognosis, such as disability and intake of acute medications [4]. Furthermore, active patient involvement would appear to be a self-help technique that could potentially lead to long-term effects [80]. Unfortunately, the lack of standardized treatment protocols leads to very heterogeneous results. ...
Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.
... and 26% reduction for the placebo group). Response rates were also significantly higher for the 150 mg Petadolex ® group (68%), but not the 100 mg Petadolex ® dose (56%), compared with the placebo (49%) (Lipton et al., 2004). ...
... The results from the two studies conducted on adults were generally positive, although efficacy in children was mixed. The pharmacological mechanisms associated with the anti-migraine effects of butterbur remains to be elucidated but may involve its antiinflammatory properties via its inhibitory influence on leukotriene synthesis, and its effects on calcium and TRPA1 channels (Benemei et al., 2017;Lipton et al., 2004). However, a concern associated with butterbur is that the raw, unprocessed butterbur plant contains chemicals called pyrrolizidine alkaloids which are toxic molecules capable of causing sinusoidal obstruction syndrome. ...
Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted. Studies were identified through electronic database searches on Medline (Pubmed), Cochrane Library, Scopus, and CINAHL. Nineteen studies were identified examining the effects on migraine of feverfew, butterbur, curcumin, menthol/peppermint oil, coriander, citron, Damask rose, chamomile, and lavender. Overall, findings on the efficacy of feverfew were mixed and there was positive, albeit limited evidence for butterbur. There were positive, preliminary findings on curcumin, citron, and coriander as a prophylactic treatment for migraine, and the use of menthol and chamomile as an acute treatment. However, the risk of bias was high for many studies. The results of this systematic review suggest that several herbal medicines, via their multifactorial physiological influences, present as potential options to enhance the treatment of migraine. However, further high‐quality research is essential to examine their efficacy and safety as a treatment for migraine.
... Rizom lopuha, Petasitidis rhizoma, primenjuje se u profilaksi migrene i kod alergijskog rinitisa, pre svega zahvaljujući prisustvu seskviterpena petazina (11,12). Primena u obliku infuza nije dozvoljena, jer sadrži značajne količine PA koji se prilikom pripreme ekstrahuju u infuz, čime bi maksimalni dozvoljeni dnevni unos PA bio prekoračen. ...
... Primena u obliku infuza nije dozvoljena, jer sadrži značajne količine PA koji se prilikom pripreme ekstrahuju u infuz, čime bi maksimalni dozvoljeni dnevni unos PA bio prekoračen. Zbog toga je razvijen specijalan tehnološki postupak ekstrakcije kojim se dobija ekstrakt koji ne sadrži PA, i za koji je u nekoliko kliničkih ispitivanja utvrđen povoljan efekat u profilaksi migrene i kod alergijskog rinitisa (11,13,14). Takav ekstrakt ulazi u sastav proizvoda na tržištu Nemačke i Švajcarske namenjenih za terapiju migrene i alergijskog rinitisa (15). ...
... Butterbur (Petasites hybridus), the subject in this study, has been reported effective in improving symptoms of migraine and allergic rhinitis via vasodilatation and anti-inflammation (21)(22)(23)(24). However, the U.K.'s Medicines and Healthcare Products Regulatory Agency issued a safety warning regarding risk of liver toxicity associated with the use of butterbur products in 2012 (25). ...
The present paper first proposes a method for ensuring the safety of commercial herbal supplements, termed the suggested daily intake-based safety evaluation (SDI-based safety evaluation). This new method was inspired as a backward analog of the acceptable daily intake (ADI) derivation from the no observed adverse effect level (NOAEL), the basis of food additive risk analysis; namely, rats are dosed with individual herbal supplement products at the SDI for human use multiplied by 100 (the usual uncertainty factor value) per body weight for 8 d. The primary endpoint is the sign of adverse effects on liver, especially gene expression of cytochrome P450 (CYP) isoforms. The proposed method was then applied to three butterbur (Petasites hybridus) products without pyrrolizidine alkaloids but lacking clear safety information. Results showed that two oily products markedly enhanced the mRNA expression of CYP2B (>10-fold) and moderately enhanced that of CYP3A1 (<4-fold) with liver enlargement. These products also caused the renal accumulation of alpha 2-microglobulin. One powdery product showed no significant effect on liver and kidney. The large difference in effects of products was due to the difference in chemical composition revealed by liquid chromatography-mass spectroscopy. The oily and the powdery products required attention in terms of safety and effectiveness, respectively. Finally, the results from the SDI-based safety evaluation of butterbur and other herbal supplement products were grouped into four categories and cautionary notes were discussed. The SDI-based safety evaluation of their products by herbal supplement operators would contribute to safe and secure use by consumers.
... Extract of butterbur (Petasites hybridus), which is used in traditional medicine, is known to have anti-migraine effects. A clinical study confirmed the preventive effect of butterbur in the treatment of migraine [93]. Nearly two decades later, isopetasin, an active component of butterbur, was shown to have a desensitizing effect on TRPA1, which effect is suggested to be responsible for the anti-migraine action [94]. ...
Recently, the transient receptor potential ankyrin 1 (TRPA1) has gained more attention in migraine-related research. The involvement of the TRPA1 receptor in migraine headaches is proposed by the fact that TRPA1 may be a target of some migraine-triggering factors. Although it is doubtful that activation of TRPA1 alone is sufficient to induce pain, behavioral studies have demonstrated that TRPA1 is involved in injury- and inflammation-induced hypersensitivity. Here, we review the functional relevance of TRPA1 in headaches and its therapeutic potential, mainly focusing on its role in the development of hypersensitivity, referring to its altered expression in pathological conditions, and its functional interaction with other TRP channels.
... Plants also contains low amounts of pyrrolizidine alkaloids, mainly senecionine and intergerrimine, with hepatotoxic and carcinogenic effects, the amount of which does not depend on the content of sesquiterpenes (Wildi et al., 1998). The refined reparations of the extracts of P. hybridus root, free of pyrrolizidine alkaloids are finding an increasingly widespread pharmacological application for the prophylaxis and treatment of migraine, bronchial asthma and allergic rhinitis -diseases affecting a large number of people (Lipton et al., 2004). Extracts are also successfully used for the prevention of gastric ulcer, urinary tract irritation and respiratory problems (Ziolo & Samochowiec, 1998). ...
Biosynthesis of biologically active substances, products of secondary plant metabolism is highly sensitive to various geographic, ecological and phenological factors. Clarification of these relationships is essential to define their impact on the efficacy and therapeutic potential of phytochemical preparations of medicinal plants. The aim of this study was to investigate the variation in the pattern of the main biologically active compounds of Petasites hybridus (L.) (Butterbur), classified as sesquiterpene esters of petasin and iso-petasin, in natural population from different habitats in Bulgaria. The results from TLC analysis confirmed the petasin chemo-type of Butterbur plants from the investigated areas. HPLC analysis revealed qualitative and quantitative differences of the six main sesquiterpene esters found in leaf and subterranean parts extracts. The investigated Bulgarian populations of Petasites hybridus have a relatively high content of petasin in the roots and are relatively poor in petasin content in the leaves. The present results indicate modulations in the profile and accumulation of secondary metabolites in Petasites hybridus, reflecting adaptive responses to specific environmental conditions in their natural habitats.
... Main biologically active compounds are secondary metabolites classified as sesquiterpene esters of petasin and isopetasin. Purified preparations of P. hybridus roots, free of pyrrolizidine alkaloids are finding an increasingly widespread pharmacological application for the prophylaxis and treatment of migraine, bronchial asthma and allergic rhinitisdiseases affecting many people (Lipton et al., 2004). Extracts are also successfully used for the prevention of gastric ulcer, urinary tract irritation and respiratory problems (Ziolo & Samochowiec, 1998). ...
The aim of this study was to relate annual variation in the structure and the functional
performance of photosynthetic apparatus of a local population of medicinal plant Petasites hybridus (L.) to
environmentally induced constraints in its natural habitat. The comparative analyses of chlorophyll
thermoluminescence (TL) and photosynthetic oxygen evolution, used to assess functionality and
recombination events of PSII reaction centres revealed specific changes in correlation to the climate
conditions during the seasons. The analysis of lipid classes and fatty acids composition of
monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyl
diacylglycerol (SQDG) and phosphatidyldiacylglycerol (PG) show the existence of qualitative and
quantitative differences that can contribute in this regard. The obtained results are discussed in terms of a
possible relationship between seasonal variation of photosynthetic performance and modulation in the
profile and accumulation of secondary metabolites with therapeutic activity in this medicinal plant.
... Meperidina, tramadol, e nalbufina são usadas para enxaqueca, porém além de provocar dependência causam: tontura, sedação e náusea(Kelley & Tepper, 2012).Importante: medicamentos opiáceos são controlados e, portanto, o farmacêutico não pode receita-los.Os pacientes devem ser instruídos a tomar a medicação de forma correta; Prescrever uma dose baixa, que deve ser aumentada lentamente;Pedir para o paciente preencher o diário para dor de cabeça (comentado anteriormente).Butterbur (Petasites hybridus -figura 9.8) (Antilerg®): é útil para prevenir ataques de enxaqueca(Agosti et al., 2006;Grossmann & Schmidramsl, 2000;Lipton et al., 2004). É uma planta, com folhas medindo 40 por 80 centímetros, que cresce em regiões montanhosas da Europa. ...
Clínica e
Prescrição
Prof. Dr. Ricardo de Souza Pereira, Ph.D.
Compilação de aulas das
faculdades de
dos EUA, Europa e Ásia
Farmácia e Medicina
Inovador e atualizado
Clínica e Prescrição
2014 by Ricardo de Souza Pereira.
Todos os direitos reservados. Nenhuma parte desta publicação pode ser reproduzida, apropriada e
estocada, por qualquer forma ou meio, sem autorização, por escrito, do detentor do Copyright.
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FIcha Catalográfica feita pelo autor
Pereira, Ricardo de Souza, 1965-
Clínica e prescrição / Ricardo de Souza Pereira. – Belo Horizonte: Rona, 2014.
236p.:18x20cm
ISBN:978-85-917770-0-6
1. Clínica. 2. Prescrfição farmacêutica. 3. Farmacologia clínica. I. Tìtulo.
CDD: 610
CDU: 616-03
P436c
2014
Capa: José Roberto da Silva Lana
Revisão linguística: Ricardo de Souza Pereira
Editoração eletrônica: José Roberto da Silva Lana
Impressão e acabamento: Rona Editora
Este livro foi impresso em papel Couchê 115g/m2
(miolo) e cartão supremo 250g/m2
(capa).
Clínica e Prescrição
Prof. Dr. Ricardo de Souza Pereira, Ph.D.
Belo Horizonte
Edição do Autor
2014
1ª edição
... The most commonly reported side effects were gastrointestinal, but no side effect was found to be significantly different for butterbur at varying doses or for placebo, with the exception of eructation. 73 An open prospective trial in children also found butterbur to be effective for migraine prevention. Children and adolescents ages 6-17 were included (N 5 108). ...
... Some data suggest that feverfew may have a small positive effect on migraine prophylaxis, but other studies are negative (level of evidence for efficacy unknown) [19]. Studies show that butterbur is effective in the prophylaxis of migraine (level of evidence moderate) [20,21] but preparations are heterogeneous with a risk of hepatotoxicity in those containing pyrrolizidine alkaloids. ...
The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the third part of the guidelines, which is focused on the non-pharmacological treatment of migraine, including physical exercise, dietary supplements and plants, diets, neuromodulation therapies, acupuncture, behavioral interventions and mindfulness therapy, patent foramen ovale closure and surgical nerve decompression.
... The Petasites extracts are successfully used for the prevention of gastric ulcer, urinary tract irritation and respiratory problems [2]. They also find an increasingly widespread pharmacological application for the prophylaxis and treatment of migraine and tension headaches, bronchial asthma and allergic rhinitis -diseases affecting a large number of people [7]. The active ingredients and action mechanism are the subject of intense research in clinical trials. ...
In this study, we present initial data for the potential anti-cancer effects of standardized Bulgarian Petasites hybridus root extract against breast cancer cells. The results showed that Butterbur extract (BE) caused a dose-dependent selective reduction in viability with concomitant increase of apoptosis in human breast cancer cells after 72 h treatment. We found the highest cytotoxicity of BE to MDA-MB-231 cells (IC50 – 520 μg/mL), followed by the MCF-7 cancer cell line (IC50 – 865 μg/mL). At the same time, the extract exhibited very low cytotoxicity to the non-tumorigenic L929 cell line (two-fold higher inhibitory concentration – 1252 μg/mL). As a result of our experiments we made the conclusion that Butterbur root extract shows selective high cytotoxicity and nucleus alterations in cancer cells comparing to non-cancerous cells.
... No Brasil já foi disponível, no seu extrato Ze339, posicionado para o tratamento da rinite alérgica (Antilerg), porém retirado do mercado por questões estratégicas da empresa. Sendo eficaz e bem tolerado na prevenção da enxaqueca (12) e também pelo seu potencial de tratamento nas rinites alérgicas que podem estar associadas às enxaquecas em um número representativo de pacientes, (13) a disponibilidade deste composto é desejável para o nosso meio. ...
There are some options for the treatment with drugs that are useful and desirable in clinical practice in Headache Medicine, which are no available to the Brazilian doctors, such as methysergide, intravenous indomethacin, melatonin, Petasites hybridus, prochlorperazine, dihydroergotamine, intravenous aspirin and new triptans. There is a need for a change in public drug approval policies taking into account the needs of our patients rather than financial issues.
... Beside many other compounds included in butterbur, two major compounds (petasin and isopetasin) are suggested to be responsible for the pharmacological effects of butterbur [31,32]. The extracts from butterbur are used to treat a variety of ailments including spasms of the urogenital and digestive tracts, asthma, migraines, and allergic rhinitis [33][34][35]. The current study pointed out that butterbur extract is a potent inhibitor of hypersensitivity induced by ovalbumin. ...
The liver is the most vital organ that could be influenced by inducers of hypersensitivity such as ovalbumin. The current study was carried out to explore the effects of butterbur (Petasites hybridus) extract on the ovalbumin-induced liver hypersensitivity in Swiss albino male mice. Animals were divided into 4 groups, 1st group served as a control group, 2nd group treated with daily oral administration of 75 mg/kg of butterbur extract, 3rd group received single oral dose 100 mg/kg of ovalbumin to induce hypersensitivity, and 4th group treated with oral administration of butterbur extract one-day post to the hypersensitivity induction. Ovalbumin induces a significant increase in the activity of liver enzymes and MDA and decreased the activity of CAT after the ovalbumin treatment. Histopathological investigations revealed marked pathological alterations in liver tissues in the form of hyaline degeneration and fibrosis. Additionally, heavy immune response indicated by immunostaining of MDA and TNF-α could be observed. In contrast, posttreatment with butterbur extract after hypersensitivity induction resulted in a significant decrease of liver enzymes and oxidative stress and reduced the inflammation and fibrosis of liver tissues. These results suggest that butterbur extract is considered as anti-inflammatory and antioxidant therapeutic herb for hypersensitivity treatment of liver.
... This study was a novel attempt at one such modification, by the addition of petasin, an extract from the perennial shrub, butterbur, that has been used in the medicine for various ailments. [10][11][12][13] Petasin has been evidenced to have a range of anti-inflammatory and analgesic properties. [14,15] The butterbur root extract (Petadolex) is a standardized special lipophilic extract of the rhizome of P. hybridus with a minimum content of 15% petasin. ...
Objective:
Zinc oxide eugenol (ZOE) is one of the most commonly used root canal sealer. However, it has few drawbacks such as cytotoxicity, solubility, and irritation to periapical tissues. The scope of this study was to investigate the setting time, solubility, cytotoxic effects, and anti-inflammatory action of ZOE sealer with the modification of its liquid component by the addition of petasin extract in the ratios 1:1, 5:1, and 10:1.
Materials and methods:
Setting time was evaluated using the Vicat's apparatus. For testing solubility, the American Dental Association's specification #8 was adopted with certain modifications. Protein denaturation assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay with L929 mouse fibroblast cell lines were used to evaluate the anti-inflammatory property and cytotoxicity, respectively.
Results:
ZOE sealer with petasin extract in the ratio of 5:1 showed the least initial and the final setting times. There was no statistically significant difference in the amount of solubility for all the groups at the various time intervals. The cytotoxicity of the control group was significantly greater than all the experimental groups, whereas the anti-inflammatory effect of the former was statistically lower.
Conclusions:
The combination of ZOE with petasin extract in the ratio of 5:1 showed lower setting time, cytotoxicity, and better anti-inflammatory property.
... In Europe and America, it is known as butterbur (P. hybridus), which has been reported to have effects on migraine, (7)(8)(9) bronchial asthma, (10) and seasonal allergic rhinitis and has been used as an herb. (11)(12)(13) Therefore, the anti-allergic effect of P. japonicus has been researched extensively. ...
Petasites japonicus (P. japonicus) is a plant of the Asteraceae family. Its roots and stems have been used for the treatment or the prophylaxis of migraine and tension headache as a traditional Chinese medicine in Japan and Korea. Sesquiterpenoids, lignans, and flavonoids are components of P. japonicus. Regarding the biological activity of P. japonicus, its anti-allergic effect has been researched extensively using IgE antigen-stimulated degranulation of RBL-2H3 cells or passive cutaneous anaphylaxis reaction in experimental animal models. The study of the antioxidant activity of P. japonicus was initiated approximately 15 years ago using in vitro assays. In addition, its in vivo effect has also been examined in animal models with induced oxidative injury. Moreover, recently, many types of antioxidant compounds have been rapidly and simultaneously identified using the liquid chromatography–mass spectrometry technique. The number of reports on the other functions of this plant, such as its neuroprotective and anti-inflammatory effects, has been increasing. In this review, I summarized the studies of functional foods derived from P. japonicus, which may provide a basis for the development of potential functional foods. Finally, I discuss the future research avenues in this field.
... It is used in the prophylaxis of migraine in children. A small study of 100 mg/day and a larger one of 150 mg/day vs placebo have shown efficacy [66]. ...
Migraine characterized by recurrent headache episodes presents with aura or without. Various treatment modalities ranging from 5-HT1B/1D agonists, nonsteroidal anti-inflammatory drugs (NSAIDs), to steroids are available for acute treatment of migraine. Prophylaxis for chronic cases usually encompasses β blockers, calcium channel blockers, and antiepileptics. Many nutraceutical preparations are helpful in migraine, including riboflavin and vitamin B12. This review focuses on the newer agents available for treatment of migraine with some insights into their clinical trials.
... Extracts of the butterbur plant (Petasites hybridus) with the main component isopetasin have long been used as preventives for migraine [177]. Isopetasin has been shown to induce calcium signals and inward currents in rodent trigeminal ganglion neurons and CGRP release from mouse dorsal spinal cord via activation of TRPA1 receptor channels, while pre-exposure to isopetasin attenuated responses to the TRPA1 agonist allyl isothiocyanate and the TRPV1 agonist capsaicin in these preparations. ...
Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating meningeal tissues. Many of these nociceptors also contain vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. Release of neuropeptides and other functional properties are frequently examined using the cell bodies of trigeminal neurons as models of their sensory endings. Pathophysiological conditions cause phosphorylation, increased expression and trafficking of transient receptor potential (TRP) channels, neuropeptides and other mediators, which accelerate activation of nociceptive pathways. Since nociceptor activation may be a significant pathophysiological mechanism involved in both peripheral and central sensitization of the trigeminal nociceptive pathway, its contribution to the pathophysiology of primary headaches is more than likely. Metabolic disorders and medication-induced painful states are frequently associated with TRP receptor activation and may increase the risk for primary headaches.
... Uluslararası baş ağrısı derneğinin migren kriterlerine uyan 245 migren hastasında standart ekstresi profilaksi değerlendirmesi amacıyla incelenmiş ve ekstre ile tedavi edilen grupta migren atak sıklığının yüzdesinde azalma olduğu saptanmıştır. Dört aylık tedavi sürecinde günde iki kez 75 mg ekstre alan hastalarda migren atak sıklığında %48 azalma, günde iki kez 50 mg ekstre alan hastalarda migren atak sıklığında %36 azalma görülmüştür [36]. ...
... Several class I studies have reported effectiveness of butterbur in decreasing headacheattack frequency. Of these, the most cited one is by Lipton et al where 100 mg and 150 mg twice daily of butterbur was compared to placebo in a 16-week trial following a 4-week baseline period in 233 subjects with migraine 41 . Subjects who took the 150 mg dose of butterbur showed a significantly higher response rate at 4 months and a greater reduction (by 45%) in attack frequency from baseline compared to the 100 mg dose (32%) and placebo (28%). ...
Background:
Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options.
Evidence acquisition:
With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention.
Results:
Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise.
Conclusions:
This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.
Background
Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression.
Methods
We conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥ 50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders.
Results
A total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho = 0.32, p = 0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho = 0.08, p = 0.596). Placebo response also varied by route of administration.
Conclusion
Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.
Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases.
This book set explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, molecular modelling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice.
Volume 2 gives (1) a detailed overview of the sesquiterpenes polypharmacology, (2) an interesting journey around the world of cannabinoids that reveals the development of new synthetic Δ9-THC derivatives, (3) the design of specific formulations to overcome the volatility of small sized terpenes-based essential oils, (4) an update on the latest generations of endoperoxides endowed with antimalarial activity and finally (5) a summary of MedChem strategies to fix the most common issues in formulating terpene derivatives (like low potency and poor solubility).
The objective of this book set is to fulfill gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians.
Background
Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression.
Methods
We conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders.
Results
A total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho=0.32, p=0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho=0.08, p=0.596). Placebo response also varied by route of administration.
Conclusion
Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.
Complementary therapies are commonly sought for treatment of pediatric headache by primary care physicians, specialists, and parents alike. Herein, we describe the use of nutraceuticals, manual therapies, and acupuncture for headache treatment. We specifically address safety and efficacy evidence when available for children and teens.
Migraine significantly impacts individuals from all walks of life and from all around the globe. Chronic or high frequency episodic migraine has similar disability and burden on the healthcare system and can be challenging to manage. The focus of this paper is to provide an outline of the available pharmacological and non-pharmacological evidence-based strategies that clinicians can employ to build a 'toolbox' for their patients. © 2022 This article is protected by
A disease intrinsically jeopardized as migraine needs multiple management approaches in the treatment process. Thinking that the drug alone, albeit innovative, efficient, safe, can play the role of gold player can sometimes lead to error. The pharmacological management should include integration and compliance in special situations such as emergency, pregnancy, age. Therefore, it is necessary to have a holistic vision of the treatment where psychobehavioral support, and in particular cases neuromodulatory and complementary alternative medicine, can be not a substitute but an integrative part of it.
Działania niepożądane, interakcje lekowe, a także farmakooporność mogą w znacznym stopniu utrudniać farmakologiczne leczenie migreny. W związku z tym coraz częściej stosuje się niekonwencjonalne i niefarmakologiczne metody leczenia. W szczególności nieinwazyjna neuromodulacja, blokady nerwów obwodowych, nutraceutyki i metody behawioralne są dobrze tolerowane i wskazane dla określonych grup pacjentów, takich jak młodzież, kobiety w ciąży i pacjenci, którzy z różnych powodów muszą lub chcą ograniczyć farmakoterapię. Metody te są coraz częściej postrzegane jako ważna opcja terapeutyczna w leczeniu migreny, konieczne są jednak dalsze badania nad ich skutecznością, także w odniesieniu do efektów długoter minowych, zwłaszcza że skuteczności części metod niekonwencjona lnych (np. kannabinoidów) dotychczas nie zweryfikowano w dobrej jakości badaniach naukowych.
Celem pracy jest przedstawienie i omówienie głównych metod wspomagających leczenie farmakologiczne migreny na podstawie aktualnego piśmiennictwa.
Petasins are the pharmacologically active ingredients of butterbur and of therapeutic benefit in the treatment of migraine and tension headaches. Here, we summarize the pharmacology, safety and clinical efficacy of butterbur in the prevention of migraine attacks and present new data on its mode of action. We review published literature and study reports on the safety and clinical efficacy of the butterbur root extract Petadolex® and report new findings on petasins in dampening nociception by desensitizing calcium-conducting TRP ion channels of primary sensory neurons. Importantly, butterbur diminishes the production of inflammatory mediators by inhibiting activities of cyclooxygenases, lipoxygenases and phospholipase A2 and desensitizes nociception by acting on TRPA1 and TRPPV1 ion channels. It inhibits the release of calcitonin-gene related peptide (CGRP) of meningeal afferents during migraine attacks. We also evaluated the safety of a butterbur root extract in repeated dose studies for up to 6 months. A no-observable-adverse-effect-level at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats. At supratherapeutic doses, i.e., 45–90-fold MCD, we observed bile duct hyperplasia, and mechanistic studies revealed regulations of solute carriers to likely account for bile duct proliferations. Additionally, liver function tests were performed in cultures of primary human hepatocytes and did not evidence hepatotoxicity at therapeutic butterbur level and with migraine co-medications. Lastly, in randomized, double-blinded and placebo-controlled trials with Petadolex® migraine attack frequency was reduced significantly at 150 mg/day, and no relevant abnormal liver function was reported. Together, butterbur is effective in the prevention of migraine attacks by blocking CGRP signaling.
Butterbur (Petasites hybridus) is a well-studied herb proven effective for migraine prophylaxis. The American Academy of Neurology and the American Headache Society have endorsed the use of butterbur root extracts for prophylactic use in migraine headaches. This herb also has potential benefits in allergic rhinitis, asthma, bladder spasms, and prevention of gastric ulcers. Butterbur has antispasmodic, anti-inflammatory, and antihistamine properties. Caution is warranted, however, due to the herb’s pyrrolizidine alkaloid (PA) content, as PAs are known to cause hepatic veno-occulusive disease. This chapter examines some of the scientific research conducted on butterbur, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of the herb’s use in treating allergies, asthma, bladder disorders, and neurological and psychiatric conditions. Finally, the chapter presents a list of butterbur’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Although many medications are currently available in the prevention and treatment of migraines, lifestyle modifications are still recommended to modify symptoms. The role of dietary and nutritional factors in causing as well as treating headache disorders has been widely studied. In this chapter, we review research related to common food triggers and IgG food sensitivity testing to prescribe an elimination diet. Prospective studies on various types of comprehensive diets such as the ketogenic diet, the modified Atkins diet, low glycemic index diet, and low-fat diet will also be summarized. Comprehensive diets do not require the exclusion of food triggers but the quantitative adjustment of micronutrients, protein, carbohydrates, and fats. Comorbid conditions such as obesity, irritable bowel syndrome, and celiac disease will be also examined in the context of migraines and studies on condition-specific dietary modifications evaluated. Finally, brain energy metabolism in migraineurs and its relationship to nutrient deficiencies will also be discussed in conjunction with the use of nutraceuticals and phytomedicine to improve migraine symptoms.
Migraine prophylaxis is an important part of the treatment algorithm for migraine disease therapy. Prophylaxis of episodic migraine may lead to decreased frequency, severity, and distress which will prevent interruptions to daily living and reduce visits to outpatient clinics, emergency settings, and in turn increases utilization of health care dollars. Prevention of acute migraine may also lead to the prevention of chronic migraine as well as increasing quality of life. Indications for prophylaxis, in general, include multiple headaches a month, debilitating headaches, medication-overuse headaches, and interruptions to daily living. Identifying environmental, dietary, and behavioral triggers are a useful first-line approach to prophylaxis, followed by utilizing over-the-counter medications, prescription medications, novel pharmacologic treatments, nonpharmacologic therapies, alternative therapies (acupuncture, massage, nutrition), and neuromodulation which may all help with migraine prophylaxis. Even with multiple therapies, treatment options are often complex.
This chapter is a quick reference guide to commonly prescribed medications in the treatment of acute migraine, migraine prevention, and chronic migraines. Medications are broken down by class. Medications are presented with commonly prescribed doses for the treatment of migraines with dosing adjustments for different disease states and pediatric dosing when applicable. Common adverse reactions and contraindications are also included. Acute management includes nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, antiemetics, antipsychotics, ergots, calcitonin gene-related peptide (CGRP) blockers, and others. Migraine prevention and chronic migraine management include beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACE/ARBs), selective serotonin reuptake inhibitors (SNRIs), CGRP blockers. This chapter is not intended to be an exhaustive review of each medication and instead aims to serve as a guide that clinicians can reference quickly to discover what medications may benefit their patients. Clinicians are encouraged to do more research about the specifics of each medication and how it interacts with other medications the patient may be on as well as how their past medical history may influence the use of each medication.
Nutraceuticals are pharmaceutical alternatives, which many patients use for management of their migraines. The American Academy of Neurology is in the process of updating their guidelines regarding nutraceuticals due to recent safety concerns. Magnesium, Vitamin D, Riboflavin, and Coq10 are better known examples; however, the list of options is extensive. Data for nutraceuticals is limited. Further studies should be completed to assess their effect on migraine and safety of use.
Background:
Migraine is a common primary headache disorder and Episodic migraine is characterized by the occurrence of up to 14 headache days in a month. The preventive treatment of migraine is useful in patients with frequent migraine attacks, impaired activities of daily living, failure of acute pain management, disabling aura and limitations in the use of acute treatment. It is aimed at reducing headache frequency and intensity, improve response to acute treatment of migraine and improve the quality of life.
Aim:
To analyze the evidence for the efficacy and tolerability of preventive oral drugs used in the management of episodic migraine.
Methods:
A narrative review of the references were reviewed by searching the literature for the articles published in PubMed in English language using all the following MeSH keywords "preventive treatment", "preventive oral treatment", AND "episodic migraine", "migraine".
Results:
Out of articles identified in the search, 38 articles were reviewed for evidence and summarized. The various oral drugs used in the prevention of episodic migraine are antihypertensives (beta-blockers, calcium channel blockers and Angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), antiepileptic drugs (valproic acid, topiramate, lamotrigine) and other miscellaneous agents. HURT questionnaire and HALT 30 index are useful in assessing response to treatment in the follow up of migraine patients.
Conclusion:
An appropriately chosen oral drug is useful in the preventive treatment of episodic migraine. In patients, who fail to respond to the preventive treatment, it is essential to review the diagnosis of migraine, titrate the dosage and duration of preventive treatment and ensure patient compliance. In those patients who fail to respond to monotherapy, polytherapy is a useful option to be considered.
Allergic diseases such as allergic asthma, hay fever, dermatitis, food, and drug allergies have increased tremendously in the last decade with increased morbidity. The current antihistaminic drugs have some limitations in terms of safety and efficacy. Most of the allergic conditions are chronic and long-term therapy is essential. Therefore, most allergic patients seek better alternatives to synthetic antihistaminic agents. Several plants and their derived natural products have been reported as effective, safe, and cheap antiallergic agents. Additionally, several plant-derived formulas have reached the clinical trials as safe antiallergic, with similar mechanisms to synthetics drugs. In this chapter, we highlighted the relevant use of plants from folk medicine or scientific-based evidence for natural antiallergic drugs. Special emphasis is given on the natural compounds with reported antiallergic activity.
Complementary and alternative medicines such as herbal medicines are not currently part of the conventional medical system. As the popularity of and global market for herbal medicine grows among all age groups, with supporting scientific data and clinical trials, specific alternative treatments such as herbal medicine can be reclassified as a practice of conventional medicine. One of the most common conditions for which adults use herbal medicine is pain. However, herbal medicines carry safety concerns and may impact the efficacy of conventional therapies. Unfortunately, mechanisms of action are poorly understood, and their use is unregulated and often underreported to medical professionals. This review aims to compile common and available herbal medicines which can be used as an alternative to or in combination with conventional pain management approaches. Efficacy and safety are assessed through clinical studies on pain relief. Ensuing herb–drug interactions such as cytochrome modulation, additive and synergistic effects, and contraindications are discussed. While self-management has been recognized as part of the overall treatment strategy for patients suffering from chronic pain, it is important for practitioners to be able to also optimize and integrate herbal medicine and, if warranted, other complementary and alternative medicines into their care.
Headache disorders are very common in women and are classified as primary or secondary. Primary headache conditions include tension-type headaches, cluster headaches, and migraine headaches. Secondary headaches are due to underlying conditions such as medication overuse, vascular abnormalities, and intracranial conditions. Headaches are diagnosed clinically based on symptoms and physical examination, but patients with “red flag” symptoms require imaging of the brain. The treatment of primary headache disorders includes abortive and preventative therapies and lifestyle changes to reduce triggers. The primary focus of this chapter is the treatment of migraine headaches by the primary care provider. Migraines may be episodic or chronic and mild, moderate, or severe, with or without aura, with or without concerning neurologic symptoms and related or not related to estrogen. Risk of stroke, choice of contraceptives, and choices of medications and supplemental therapies used in the management of migraineurs are presented. The care of women with chronic headaches requires skill and patience, with a global approach utilizing the expertise of a team of multiple specialists and treatment modalities.
Affecting one in five people, chronic pain is a complex, multifactorial condition that is challenging for both patients and clinicians. Prevailing pain management, which includes NSAIDS and opioids, has not adequately addressed the growing cohort of those suffering and comes with serious side effects. Current Western diets are high-calorie, micronutrient-deficient and create excessive inflammation. Most pain syndromes are associated with chronic inflammation, altered gut microbiomes, drug-nutrient interactions, nutrient insufficiencies and food sensitivities. Through individual foods, nutrients and dietary patterns, nutrition has preventive, causative, managerial and curative involvement in chronic pain. Using diet and lifestyle as a first-line intervention is empowering for the pain patient, can increase function, and can be potentially transformative.
Phytomedicines may provide new options for migraine prophylaxis and treatment based on their historical use and pharmacological properties. However, as clinical data are limited, no phytomedicine can currently be strongly recommended to manage migraine. Feverfew and butterbur may be effective in preventing migraine, but the efficacy of butterbur has been overshadowed by reports of severe petasites hepatotoxicity. Although further research is needed, chamomile, coriander, peppermint and ginkgo have shown encouraging results in explorative clinical studies, and the active components of cannabis and St John’s wort have shown promise in preclinical studies.
The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one-month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects.
Seventeen patients who ate fresh leaves of feverfew daily as prophylaxis against migraine participated in a double blind placebo controlled trial of the herb: eight patients received capsules containing freeze dried feverfew powder and nine placebo. Those who received placebo had a significant increase in the frequency and severity of headache, nausea, and vomiting with the emergence of untoward effects during the early months of treatment. The group given capsules of feverfew showed no change in the frequency or severity of symptoms of migraine. This provides evidence that feverfew taken prophylactically prevents attacks of migraine, and confirmatory studies are now indicated, preferably with a formulation controlled for sesquiterpene lactone content, in migraine sufferers who have never treated themselves with this herb.
A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis. We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis. We now compared riboflavin (400 mg) and placebo in 55 patients with migraine in a randomized trial of 3 months duration. Using an intention-to-treat analysis, riboflavin was superior to placebo in reducing attack frequency (p = 0.005) and headache days (p = 0.012). Regarding the latter, the proportion of patients who improved by at least 50%, i.e. "responders," was 15% for placebo and 59% for riboflavin (p = 0.002) and the number-needed-to-treat for effectiveness was 2.3. Three minor adverse events occurred, two in the riboflavin group (diarrhea and polyuria) and one in the placebo group (abdominal cramps). None was serious. Because of its high efficacy, excellent tolerability, and low cost, riboflavin is an interesting option for migraine prophylaxis and a candidate for a comparative trial with an established prophylactic drug.
In vivo and in vitro studies were carried out to examine the putative hypotensive actions of S-petasin, a sesquiterpene extracted from the medicinal plant Petasites formosanus. Intravenous S-petasin (0.1-1.5 mg/kg) in anesthetized rats produced a dose-dependent hypotensive effect. In isolated aortic ring, isometric contraction elicited by KCl or the L-type Ca2+ channel agonist Bay K 8644 was reduced by S-petasin (0.1-100 microM), an action not affected by the cyclooxygenase inhibitor indomethacin, nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine, guanylyl cyclase inhibitor methylene blue, or removal of vascular endothelium. Pretreatment with S-petasin for 10 min shifted the concentration-response curve for KCl (15-90 mM)-induced contraction to the right and reduced the maximal response. In Ca2+-depleted and high K+-depolarized aortic rings preincubation with S-petasin attenuated the Ca2+-induced contraction in a concentration-dependent manner, suggesting that S-petasin reduced Ca2+ influx into vascular smooth muscle cells (VSMCs). Moreover, in cultured VSMCs, whole-cell patch-clamp recording indicated that S-petasin (1-50 microM) inhibited the L-type voltage-dependent Ca2+ channel (VDCC) activities. Intracellular Ca2+ concentration ([Ca2+[(i)) estimation using the fluorescent probe 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N,N-tetraacetic acid pentaacetoxymethyl ester indicated that S-petasin (10, 100 microM) suppressed the KCl-stimulated increase in ([Ca2+[(i)). Taken together, the results suggested that a direct Ca2+ antagonism of L-type VDCC in vascular smooth muscle may account, at least in part, for the hypotensive action of S-petasin.
We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca²⁺-induced contractions in depolarized (K⁺, 60 mM; histamine, 100 μM; or carbachol, 10 μM) guinea-pig tracheas. S-Isopetasin did in depolarized (K⁺, 60 mM) trachea too. The nifedipine (10 μM)-remaining tension of carbachol (0.2 μM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 μM), 2′,5′-dideoxyadenosine (10 μM), methylene blue (25 μM), glibenclamide (10 μM), N ω-nitro-L-arginine (20 μM), or α-chymotrypsin (1 U/ml). However, S-petasin (100 - 300 μM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.
Abbreviations
ROCCs:receptor-operated calcium channels
VDCCs:voltage dependent calcium channels
cAMP:adenosine 3′,5′-cyclic monophosphate
cGMP:guanosine 3′,5′-cyclic monophosphate
PDE:phosphodiesterase
IBMX:3-isobutyl-1-methylxanthine
To assess patterns of medical consultation, diagnosis, and medication use in representative samples of adults with migraine in England and the United States.
Validated computer-assisted telephone interviews were conducted in the United Kingdom (n = 4,007) and the United States (n = 4,376). Individuals who reported six or more headaches per year meeting the criteria for migraine were interviewed.
Patients with migraine in the United Kingdom were more likely to have consulted a doctor for headache at least once in their lifetime (86% vs 69%, p < 0.0001), but also were more likely to have lapsed from medical care (37% vs 21%, p < 0.001). In the United States, patients with migraine who had consulted made more office visits for headache and were more likely to see a specialist. In the United States, but not in the United Kingdom, women with migraine were more likely than men to consult doctors for headache. Patients with migraine in the United Kingdom were more likely to receive a medical diagnosis of migraine (UK 67%, US 56%; p < 0.05). Patterns of medication use were similar in both countries, with most people treating with over-the-counter (OTC) medications. Substantial disability occurred in a high proportion of those who never consulted (UK 60%, US 68%), never received a correct medical diagnosis (UK 64%, US 77%), and treated only with OTC medication (UK 72%, US 70%).
Medically unrecognized migraine remains an important health problem both in the United States and the United Kingdom. Furthermore, there may be barriers to consultation for men in the United States that do not operate in the United Kingdom.
Objective.—To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura).
Study Design and Treatment.—After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a three-times-a-day dosing regimen.
Methods.—The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor.
Results.—At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P = .006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P = .008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P = .006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P = .013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin.
Conclusion.—Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness.
The 3rd Petasites gathering took place in Romanshorn, Switzerland on March 29, 1996 and gave 16 European scientists the opportunity to transmit their latest considerable discoveries to interested researchers working in different scientific disciplines such as pharmacognosy, botany, chemistry, pharmacology, medicine or clinical pharmacy. The newest findings on Petasites hybridus as a significant plant drug showed very promising aspects of therapeutic utility. Great progress has been made in chemical analytical methods and the determination of pharmacological activities. Substantial advances have also occurred in the production of bioassay procedures and plant materials, particularly utilizing cell- and tissue-culture techniques.
An 8-month, double-blind, placebo-controlled, crossover trial of flunarizine in the prophylaxis of migraine has been performed in 70 children. After 4 weeks of medication-free base-line observation, 35 children (group A) received flunarizine (5 mg/day) and 35 (group B) received placebo over a 12-week period. After a 4-week washout they crossed treatments for another 12 weeks. Sixty-three patients completed the trial. In both groups flunarizine significantly reduced the frequency and average duration of headache attacks. In group A efficacy was maintained after placebo crossover for the last 4 months of the study. Five subjects in group B stopped placebo because of ineffectiveness; two children in group A discontinued flunarizine treatment, one because of excessive daytime sedation and the other because therapy was ineffective. The main side effects were daytime sedation and weight gain. It is concluded that flunarizine is an effective drug for the treatment of childhood migraine. In a study of this length no serious side effects were discovered.
To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache.
Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance).
Eight headache/neurology clinics throughout the United States.
One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo.
Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L.
During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant).
Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.
Extracts from Petasites hybridus are in therapeutic use for more than 2000 years. They have been claimed to improve gastrointestinal pain, lung-diseases such as asthma and cough, as well as spasms of the urogenital-tract. We have investigated these claims in animal models of gastro-intestinal ulcers and confirmed that alcoholic extracts of Petasites hybridus block the ethanol-induced gastric damage and reduce small intestinal ulcerations induced in rats by indomethacin. Searching for a possible mode of action, we found that ethanolic extracts of Petasites hybridus inhibit the peptido-leukotriene biosynthesis in mouse peritoneal macrophages but leave prostaglandin biosynthesis unimpaired. We conclude that the active principle could be useful in the treatment of gastro-intestinal human diseases and that Petasites hybridus may contribute to the inhibition of calcium-dependent processes such as leukotriene biosynthesis.
In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18-65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.
Objective:
Clinical observation of a decrease in migraine frequency in patients with comorbid asthma taking montelukast, a specific D4 leukotriene receptor antagonist, or zafirlukast, another leukotriene receptor antagonist, prompted us to explore a possible role for leukotriene modifiers in the treatment of migraine. (A further prompt was a pharmacist colleague's observation that a number of patients on these agents reported a decreased sensitivity to perfume triggers and improvement in migraine.)
Background:
Nonsteroidal anti-inflammatory agents have been used widely in the treatment of migraine. Another class of anti-inflammatory agents, known as leukotriene modifiers, have not been studied to date with regard to their possible role in the treatment of migraine. The name "leukotriene is derived both from the parent molecule, which was originally isolated from leukocytes, and from its three double-bond carbon backbone or triene structure. Both prostaglandins and leukotrienes are derived from the metabolism of arachidonic acid, with prostaglandins coming off the cyclooxygenase pathway and leukotrienes derived via the enzyme 5-lipoxygenase. Both prostaglandins and leukotrienes mediate inflammatory responses. The latter have been studied with regard to their role in the pathophysiology of asthma.
Methods:
A prospective, open-label study evaluating the efficacy of montelukast, 10 mg or 20 mg, in the prophylaxis of migraine in 17 patients is presented in this paper. All 17 patients completed the study that consisted of a 2-month baseline run-in period and a 3-month treatment phase.
Results:
Montelukast was extremely well tolerated, and no adverse events were reported by any of the patients. Fifty-three percent showed a reduction of greater than 50% (P<.025) in the frequency of severe attacks, with 41% showing a reduction of greater than 60%. Responders, including modest responders, rated the drug as excellent.
Conclusions:
We conclude, given the limitations of an open-label study design and the small sample size, that montelukast shows potential as an effective, well-tolerated prophylactic agent in migraine. Double-blinded, placebo-controlled studies are warranted. In addition, the leukotrienes, as suggested previously in the literature, may play a role in the pathogenesis of migraine.
Migraine is still an unsolved problem. This clinical trial investigates the efficacy and tolerance of Petasites hydridus in the prophylaxis of migraine.
A randomized, group-parallel, placebo-controlled, double-blind clinical study was carried out with a special CO2 extract from the rhizome of Petasites hybridus. Following a 4-week run-in phase, 60 patients received either the special Petasites hybridus extract petadolex or placebo at a dosage of 2 capsules (each capsule contains 25 mg) twice daily over 12 weeks. Outcome variables included the frequency, intensity and duration of migraine attacks as well as any accompanying symptoms.
The frequency of migraine attacks decreased by a maximum of 60% compared to the baseline. This reduction in migraine attacks with petadolex was significant (p < 0.05) compared to placebo. No adverse events were reported. Petasites was exceptionally well tolerated.
The results suggest that migraine patients can benefit from prophylactic treatment with this special extract. The combination of high efficacy and excellent tolerance emphasizes the particular value that Petasites hydridus has for the prophylactic treatment of migraine.
A large production of leukotrienes (LTs) can be induced in human eosinophils or neutrophils by priming with granulocyte-macrophage colony-stimulating factor and subsequent stimulation with platelet-activating factor (PAF) or the anaphylatoxin C5a. Here, we investigated the effects of a plant extract of petasites hybridus (Ze339) and its isolated active sesquiterpene ester petasin in these two in vitro cell models. Zileuton, a 5-lipoxygenase inhibitor, was used as a positive control. All compounds inhibited both cysteinyl-LT synthesis in eosinophils and LTB(4) synthesis in neutrophils. In contrast, only Ze339 and petasin, but not zileuton, abrogated PAF- and C5a-induced increases in intracellular calcium concentrations. These data suggest that Ze339 and petasin may block, compared to zileuton, earlier signalling events initiated by G protein-coupled receptors in granulocytes, perhaps at the level of or proximal to phospholipase C(beta). Taken together, petasin appears to be one major active compound of petasites hybridus extract, since it demonstrates the same inhibitory activities on calcium fluxes and subsequent LT generation in both eosinophils and neutrophils as Ze339 does.
Priming of eosinophils with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with platelet-activating factor (PAF) or the anaphylatoxin C5a is associated with a rapid production of leukotrienes (LTs) and release of eosinophil cationic protein (ECP).
This study was designed to determine the effects of the sesquiterpene esters petasin, isopetasin and neopetasin on LT generation and ECP release in eosinophils in vitro.
The model of eosinophil activation described above was used to induce LT production and ECP release. Cells were incubated with petasins and control inhibitors prior to priming and stimulation. To analyse intracellular steps of eosinophil activation and determine potential drug targets, some key signalling events were studied. Activity of cytosolic phospholipase A2 (cPLA(2)) was measured by analysing the generation of arachidonic acid (AA). Translocation of 5-lipoxygenase (5-LO) was observed using immunofluorescence microscopy. Intracellular calcium concentrations [Ca2+]i were measured by a bulk spectrofluorometric assay.
Whereas all three compounds inhibited LT synthesis, ECP release from eosinophils was blocked by petasin only, but not isopetasin or neopetasin. Similarly, PAF- or C5a-induced increases in [Ca2+]i were completely abrogated by petasin only, whereas isopetasin and neopetasin had significant lower blocking efficacy. Moreover, only petasin, but not isopetasin or neopetasin, prevented increases in cPLA(2) activity and 5-LO translocation from the cytosolic compartment to the nucleus envelope in calcium ionophore-stimulated eosinophils.
These data suggest that different petasins may at least partially block different intracellular signalling molecules. To reduce LT synthesis, isopetasin and neopetasin may act at the level of or distal to 5-LO. In contrast, petasin may inhibit inflammatory effector functions in human eosinophils by disrupting signalling events at the level of or proximal to phospholipase Cbeta (PLCbeta), besides its potential inhibitory activity within mitogen-activated protein kinase (MAPK) and LT pathways.
To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine.
Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine.
Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase.
During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment.
Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.
AN 80-YEAR-OLD woman presented with a left C7 radiculopathy. Cervical magnetic resonance imaging showed spinal stenosis at the C7 through T1 vertebrae, with anterolisthesis. The patient underwent posterior C7 decompression laminectomy, C7-T1 foraminotomy, and spine stabilization with posterior fusion of the C7 through T1 vertebrae with pedicle screws and local autogenous bone graft. The patient awoke with marked bilateral upper extremity weakness, worse on the left side, with anesthesia in the bilateral medial forearms and digits 4 and 5. Biceps and triceps reflexes were absent bilaterally, but other reflexes were normal in the lower extremities. Plantar responses were extensors.
To report on the safety of a patented special butterbur root extract used for migraine prevention.
Two placebo-controlled clinical trials have been conducted supporting the beneficial use in humans.
Results from acute, subchronic and chronic animal toxicity studies as well as from mutagenicity studies are reported. Safety data gained from clinical trials, postmarketing surveillance studies and pharmacovigilance are evaluated and discussed.
The patented special butterbur root extract is safe for the treatment in humans.
This is an independent reanalysis of a randomised, placebo-controlled parallel-group study on the efficacy and tolerability of a special butterbur root extract (Petadolex) for the prophylaxis of migraine. The original protocol and analysis had a number of major shortcomings. In order to follow regulatory requirements, an independent reanalysis of the original data was performed. Following a 4-week baseline phase, 33 patients were randomised to treatment with two capsules 25 mg butterbur twice a day and 27 to placebo. The mean attack frequency per month decreased from 3.4 at baseline to 1.8 after 3 months (p = 0.0024) in the verum group and from 2.9 to 2.6 in the placebo group (n.s.). The responder rate (improvement of migraine frequency > or =50%) was 45% in the verum group and 15% in the placebo group. Butterbur was well tolerated. This small trial indicates that butterbur may be effective in the prophylaxis of migraine.
Drug treatment for the pre-vention of migraine headache Prepared for the Agency for Health Care Policy and Research under contract number 29009402025. Available from the National Technical Information Service; NTIS accession no
- Gray Rn Re Goslin
- Mccrory
- Dc
Gray RN, Goslin RE, McCrory DC, et al. Drug treatment for the pre-vention of migraine headache. Technical review 2.3, February 1999. Prepared for the Agency for Health Care Policy and Research under contract number 29009402025. Available from the National Technical Information Service; NTIS accession no. 127953.
Preventive treatment for childhood and adoles-cent headache: role of once-daily montelukast sodium
- Em Pearlman
- Fisher
Pearlman EM, Fisher S. Preventive treatment for childhood and adoles-cent headache: role of once-daily montelukast sodium. Cephalalgia 2001;21:461.
Behandlung von Koliken und Spasmen in der Urologie mit einem pflanzlichen Spasmolytikum
- S Barsom
Barsom S. Behandlung von Koliken und Spasmen in der Urologie mit einem pflanzlichen Spasmolytikum. Erfahrungsheilkunde 1986;35:1–11.
Prepared for the Agency for Health Care Policy and Research under contract number 29009402025. Available from the National Technical Information Service
- R N Gray
- R E Goslin
- D C Mccrory