Chinese herbal medicine therapies for migraine: current state of evidence, impact on practice, and a real-world setting evaluation
Creators: name: Lyu, Shaohua
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 420803
subject: Traditional Chinese medicine and treatments

description: Background
Migraine is the second-most disabling condition worldwide and the most disabling among young females aged under 50 years. Migraine often elicits suboptimal responses and undesirable adverse events (AEs) from conventional pharmacological interventions. The concurrent presence of comorbidities and the excessive use of acute medication further compromise the limited treatment effects and result in migraine chronification. In this context, there is a critical need for alternative therapeutic options that are effective and better tolerated by patients, especially for those with complex comorbidities. 
Chinese medicine is a holistic medical system that emphasises dynamic and ongoing syndrome differentiation. Chinese medicine prescriptions for migraine are tailored based on a comprehensive analysis of migraine history, severity, accompanying symptoms, comorbidities and triggers. Chinese medicine, especially Chinese herbal medicine (CHM), has been widely prescribed to over 60% of outpatient migraine patients in China. The successful experience of treating migraine related presentations using Chinese medicine has accumulated for thousands of years. In addition, several well-known and frequently used CHM prescriptions have been shown to be beneficial in clinical trials. In the framework of evidence-based practice (EBP), it is essential to comprehensively evaluate the current state of clinical evidence by integrating historical and contemporary clinical expertise, research evidence from controlled settings and real-world practice, and patients’ preferences and values from real-world practice, to support informed clinical decision-making on Chinese medicine for migraine.
 
Research aim, objectives and research questions
The primary research aim of this project is to establish a comprehensive and coherent integration of clinical expertise, research evidence and patients’ preferences and values to further support the EBP of CHM for migraine.
The specific objectives of this project are:
1) To establish robust research evidence on the effectiveness and safety of CHM for migraine in both controlled research settings and real-world clinical practice 
2) To summarise clinicians’ expertise from classical Chinese medicine literature and real-world contemporary medical records 
3) To collect patients’ preferences and values in seeking CHM for migraine from retrospective analyses of medical records and a prospective registry-based cohort study
The research questions proposed for this project to accomplish these aim and objectives are:
1) How has migraine been managed with Chinese medicine in ancient and contemporary clinical practice?
2) Is CHM effective and safe in alleviating migraine symptoms and managing comorbidities in controlled research settings and real-world clinical practice? 
3) What are the preferences and concerns of migraine patients when seeking Chinese medicine for migraine? 

Methods and results
The project has been designed in accordance with the three components of EBP, encompassing a data-mining study of classical literature, two systematic reviews based on randomised controlled trials (RCTs), a retrospective analysis of medical records and a prospective observational study.

1) Data-mining of classical Chinese medicine literature
This study employed well established and validated methodologies developed by the China-Australia International Research Centre for Chinese Medicine including using the Encyclopedia of Traditional Chinese Medicine 5.0. The citations were scored using modified criteria based on the diagnostic criteria for migraine without aura, which ensured their relevance to migraine. Oral CHM was the most recorded therapy, compared to intranasal and topical applications of CHM and to acupuncture. Frequency analyses revealed that chuan xiong was the most frequently orally administered herb and Chuan xiong cha tiao san (CXCTS) was the most frequently used oral formula for migraine. Association rules indicated that symptoms of vomiting and nausea were associated with the herbs sheng jiang and ban xia. Results of oral CHM for migraine in classical literature have been published in a journal article entitled ‘Natural products for migraine: Data-mining analyses of Chinese medicine classical literature’. 

2) Evaluation of clinical evidence by systematic reviews
The project also undertook two systematic reviews to update the latest clinical research evidence on oral CHM for migraine in controlled settings, following the Cochrane Handbook 5.1.0. Nine major English databases were searched to identify the relevant RCTs. Meta-analyses were conducted using R 4.0.5, Review Manager 5.3 and Stata 12.0 software, and certainty of evidence was determined using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). The first systematic review compared the effectiveness and safety of oral CHM to flunarizine and found that CHM was at least equivalent in effectiveness and safety to flunarizine for migraine prophylaxis, and identified chuan xiong to be the most frequently used herb from the included RCTs. The second systematic review evaluated the efficacy of CHM to placebo and confirmed that CHM was efficacious and safe for migraine, and that the treatment effects expanded as treatment duration extended from 4 weeks to 12 weeks. Both systematic reviews have been published. 

3) Retrospective analysis of medical records
This study retrospectively analysed migraine-related medical records from the Guangdong Provincial Hospital of Chinese Medicine (GPHCM), finding that the herb chuan xiong and the formula CXCTS were consistently used since ancient times. Other herbs such as fu ling, gan cao, bai zhu, etc. were also frequently used in clinical practice. In contrast, non-orally administered CHM were rarely used in contemporary clinical practice. Patented Chinese herbal medicine products (PCHMPs) emerged as convenient treatments for migraine and the most frequently used one was Tong tian oral solution. The analyses also revealed a low level of treatment adherence in real-world clinical practice. Results of this study have been published in a journal paper entitled ‘Chinese herbal medicine for migraine management: A hospital-based retrospective analysis of electronic medical records’.

4) Prospective cohort study in real-world clinical practice
This study prospectively registered migraine patients to observe clinical practice of CHM for migraine, evaluate real-world outcomes of CHM for migraine and survey patients’ preferences and values. The outcomes highlighted that CHM’s effectiveness in reducing migraine severity and comorbid anxiety while enhancing patients’ quality of life, at a minimum treatment duration of 28 days. Patients expected CHM to be effective for migraine severity and managing comorbidities, but only a few patients expected to reduce their use of acute medications. Patients were primarily concerned about the potential side effects of CHM. Adherence and persistence with treatment were inadequate. The herb chuan xiong was consistently prescribed in clinical practice. Various PCHMPs were prescribed to alleviate migraine symptoms and associated comorbidities. Protocol of this study has been published in journal paper titled ‘Migraine patients visiting Chinese medicine hospital: Protocol for a prospective, registry-based, real-world observational cohort study’. 

Conclusion
This project has synthesised a comprehensive evidence map incorporating clinical expertise, classical and modern research evidence and patients’ preferences, feedback and values. Patients’ expectations primarily centred on alleviating migraine severity and comorbidities, while their apprehensions revolved around potential side effects. Oral CHM was found to be effective for migraine in reducing severity and acute medication usage, as well as improving quality of life, with few AEs. The effects could be achieved at a minimum treatment duration of 28 days and enhanced with prolonged treatment. The herb chuan xiong stood as a prevalent prescription choice as the key ingredient, often in combination with other herbs selected based on CHM theory. PCHMPs can be prescribed as a more convenient and increasingly prevalent option for the purpose of managing migraine episodes and their associated symptoms and comorbidities.