Abstract: According to the Global Burden of Disease (GBD) study, headache is one of the most prevalent and disabling diseases in the world, including general headaches, migraines and tension headaches, of which the prevalence of migraines is increasing. Migraines have become a worldwide problem, and their harm is equivalent to Alzheimer's disease and serious mental illness.
According to the 2019 Global Burden of Disease (GBD) study, migraine alone ranks second among the causes of disability and first among women under 50 years of age, which is enough to see the dangers of migraines. The director of the Pain Department of Sanbo Brain Hospital of Capital Medical University once reminded that migraines cannot be tolerated, and when they have affected life and work, they need to seek medical treatment in time.
Every year, 52% of people worldwide suffer from headaches
It is particularly female-oriented
A team of researchers led by epidemiologists at the Norwegian University of Science and Technology summarized epidemiological headache studies published between 1961 and 2020 and found that 52% of people worldwide suffer from some form of headache disorder[1], with the findings "The global prevalence of headache: an update, with analysis of the influences of methodological." factors on prevalence estimates" (Figure 1), published in The Journal of Headache and Pain.
Figure 1 Research results (Source: [1])
For the study, the researchers obtained a partial selection of research papers on headache prevalence published up to 2020 through a literature search. Using pooled data analysis, the researchers concluded that globally, the overall prevalence of headache disorders is 52 percent, of which migraines are 14 percent and tension headaches are 26 percent [1]. The authors also note that 15.8% of people globally are suffering from headaches every day.
In addition, the researchers found that:
All headache types are more common in the female population, while migraines have the greatest differences between the sexes (17% in women and 8.6% in men);
Women are more likely to report headaches as persistent health problems, with 6 percent saying they have headaches lasting 15 days or more a month, compared to only 2.9 percent of men who do the same.
Lars Jacob Stofner, a neuroscientist at the Norwegian University of Technology, said: "The prevalence of headache diseases remains high globally, and we should take measures to reduce the burden of this disease through prevention and treatment. In order to assess the effectiveness of these measures, we must effectively monitor the incidence and burden in different societies. ”
Pathogenesis of migraine
with common triggers
1. Pathogenesis of migraine
●Vascular theory
Vascular theory suggests that the symptoms of migraine are caused by vasodilating dysfunction, based primarily on changes in the level of vasoactive substances such as serotonin (5-HT) at the onset of migraine [2]. However, this mechanism cannot be fully explained for other features of migraine, such as unilaterality, aura, and concomitant symptoms. Coupled with the effective use of a series of non-vascular drugs such as topiramate and valproate, the vascular theory has been questioned, and migraine is no longer a simple "vascular headache" [3].
●Cortical diffusion inhibition (CSD) theory
CSD essence is an electrophysiological phenomenon caused by local neuronal excitation in the cerebral cortex, and the phenomenon of excessive depolarization wave diffusion spreads from the local to the surrounding. With the introduction of CSD, many scholars began to think that the vascular changes of migraine were secondary to nerve cell dysfunction, and by observing the structural and functional changes of some specific brain areas during the onset of migraine, it was confirmed that vascular changes were secondary to neurological changes, and the pathogenesis of migraine began to gradually shift to peripheral and central pain pathway research [2].
●Trigeminal Neurovascular Theory (TVS)
The TVS theory believes that migraines occur because of functional defects in the trigeminal neurovascular system and the endogenous analgesic system of the central nervous system, coupled with internal and external stimulation. When the trigeminal nerve is stimulated, it can release a variety of vasoactive substances, such as calcitonin gene-associated peptides (CGRP), P substances, etc., which in turn lead to extravasation of plasma components, platelet activation, and vasodilation [2].
2. Common triggers of migraine
Migraine is an episodic disorder that is often associated with a variety of triggers, including sleep deprivation, food additives, alcohol, caffeine, fasting, artificial sweeteners, substance abuse, mental stress, and obstructive sleep apnea syndrome. In addition to these, there are also some migraine patients because of family genetics, accounting for about 60%, such patients and their immediate family members have a 3-6 times risk of migraines than the general population. In addition, for women, there are also migraines caused by endocrine and metabolic factors, which generally occur occasionally during female puberty, often occur during menstruation, and will gradually reduce or even no more seizures after pregnancy or menopause in women.
How can migraines be effectively diagnosed and managed?
Although headaches and migraines are prevalent, they are currently under-diagnosed and treated. To support clinical decision-making on migraine, the consensus statement "Diagnosis and management of migraine in ten steps" (Figure 2), initiated by the Danish Headache Association and supported by the European Headache Federation and the European Society of Neurology, was published in Nature Reviews Neurology in 2021.
Figure 2 Research results (Source: [4])
In this consensus statement, a team of European experts developed a ten-step approach to migraine diagnosis and management (Figure 3). The purpose of this approach is to support care and clinical decision-making by primary care physicians, neurologists and headache specialists.
Fig. 3 Ten-step method for migraine diagnosis and management (Source: [4])
The ten-step approach to migraine diagnosis and management includes: when to suspect migraine; to diagnose migraine; to educate and patient-centered; to treat acutely; to preventative treatment; to manage migraine in special populations; follow-up, response to treatment, and failure; to manage complications; to identify and manage comorbidities; and to follow up with long-term follow-up.
In clinical practice, migraines are often treated with analgesics, including ibuprofen, acetaminophen, aspirin, diclofenac and naproxen, but long-term use of such drugs will have gastrointestinal reactions and bleeding risks, and even cause damage to the liver and kidneys. In addition, treatment is carried out with triptans and specific pain relievers such as ergotamines. It is important to note that patients with uncontrolled hypertension, ischemic heart disease, and coronary artery spasms should not use triptans; in addition, very small amounts of ergotamine can quickly lead to drug overdose headaches, so the frequency of use of these drugs should be limited and routine use is not recommended [5].
It is worth mentioning that the discovery of the key target of calcitonin gene-associated peptides (CGRP) has led to a breakthrough in the preventive treatment of migraine. CGRP receptor antagonists reduce migraine symptoms by restoring the dilated meningeal arteries to normal without causing vasoconstriction, so there are no side effects.
1. NURTECODT that integrates prevention and treatment in one "tablet"
NURTECODT (Rimegepant), developed by Biohaven, is the first and only CGRP receptor antagonist with a rapidly dissolving oral disintegration tablet form, and the only oral CGRP receptor antagonist approved for both the treatment and prevention of migraines. Rimegepant was approved for fda listing in 2020 for acute treatment of migraine in adults and was approved as a new indication for preventive treatment of migraine in May 2021. Long half-lives, good oral bioavailability, and high affinity for CGRP receptors make it a potential best-in-class anti-acute migraine drug [6].
In a 2021 study published in The Lancet (Figure 4), researchers compared the efficacy of Rimegepant and placebo in preventing and treating migraines. In this study, subjects were randomly assigned to the Rimegepant group (348) and placebo groups (347) to take Either Rimegpant or placebo daily for 12 weeks. The researchers found that Rimegepant was superior to the placebo group in terms of changes in the average number of migraine days per month over weeks 9 to 12, with patients in the Rimegepant group having an average number of migraine days decreasing by 4.3 days per month and placebo by 3.5 days [7].
Figure 4 Research results (Source: The Lancet)
Oral CGRP-targeted drugs show strong growth momentum compared to triptans, so Rimegepant has huge market potential.
2. Novartis' new drug for heavy migraines, Erenumab
Erenumab is a fully human monoclonal antibody developed by Amgen and Novartis to prevent migraines by blocking the activity of calcitonin gene-associated peptides (CGRP). Erenumab was approved for marketing by the FDA in May 2018, becoming the first approved antagonist against CGRP receptors, and in July of the same year, Erenumab was listed in the European Union. In March 2021, Novartis announced positive results in the DRAGON Phase III study, reaching the primary endpoint. A randomized, double-blind, multicenter, placebo-controlled Phase III clinical trial to evaluate the efficacy and safety of Erenumab in the prophylactic treatment of chronic migraine in adults, enrolled 557 patients and was predominantly Asian-centric and Chinese-based.
The data showed that the Erenumab group was significantly better than the placebo group at the last 4 weeks of the 12-week double-blind treatment period compared with the baseline reduction in the number of migraines per month (MMD) at the efficacy endpoint (primary endpoint). Moreover, the response rate of more than 50% reduction in the number of migraines per month in the Erenumab group compared to baseline was significantly higher than that in the placebo group, and no serious adverse events were found during the experiment. At present, no CGRP drugs have been approved in China, and Novartis' Erenumab is expected to become the first in China.
Migraines are affecting more and more people, and there is a trend of rejuvenation, which has a certain negative impact on our lives and work, which should be paid attention to. In daily life, pay attention to sleep and rest, avoid excessive fatigue; pay attention to the precursors and symptoms of migraines, and seek medical attention in time once discomfort is found. Because migraines are particularly favored by women, women should pay special attention to the prevention of migraines, maintain healthy eating habits and living habits during menstruation, and ensure adequate sleep. At the same time, you should also avoid taking some drugs and foods that induce migraine attacks, such as cured meats, cheeses, chocolates containing phenylethylamine, snacks containing sodium glutamate, etc.
Written by | Muzijiu
Typography | Qiao Weijun
End
Resources:
[1] Stovner LJ, Hagen K, Linde M, et al. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022 Apr 12;23(1):34. doi: 10.1186/s10194-022-01402-2. PMID: 35410119; PMCID: PMC9004186.
Zhou Xia,Sun Zhongwu. Pathogenesis and diagnosis and treatment progress of migraine[J].Chinese Journal of General Medicine,2019,17(05):714-715.
Ye Shenqiong,Wang Xiangming,Zhang Yuehui. Research progress on the pathogenesis of migraine[J].Medical Review,2020,26(06):1086-1091.
[4] Eigenbrodt AK, Ashina H, Khan S, et al. Diagnosis and management of migraine in ten steps. Nat Rev Neurol. 2021 Aug;17(8):501-514. doi: 10.1038/s41582-021-00509-5. Epub 2021 Jun 18. PMID: 34145431; PMCID: PMC8321897.
[5] Migraine attacks, drugs are not used wrong
https://wsjkw.sh.gov.cn/jtyx/20200909/7281b78afd064d2e88c39ce08141c6c0.html
[6] Rimegepant: The second oral anti-migraine CGRP formulation, available in the United States, is expected to sell more than Ubrogepanthttps://mp.weixin.qq.com/s/AUhghT4_x79TpAlqLEtrSA
[7] Croop R, Lipton RB, Kudrow D, et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021 Jan 2;397(10268):51-60. doi: 10.1016/S0140-6736(20)32544-7. Epub 2020 Dec 15. PMID: 33338437.
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