1,1 Introduction
Migraine is one of the common diseases in neurology, in the United States: about 18% of women and 6% of men have had migraine attacks, but most of them are not formally diagnosed and treated, and some of them seriously affect the quality of life of patients [7].
1,2 Clinical issues
(1) Neuroimaging of migraine: how does neuroimaging help to detect the cause of headache? What is the rate of intracranial abnormalities found on neuroimaging in non-acute headache patients with normal investigations? What is the relative sensitivity of CT and MRI in detecting intracranial abnormalities in non-acute headache patients? (2) Migraine control: What is the role of medication in migraine during attacks? What is the effect of drug prevention on the severity and frequency of migraine attacks? What is the safety and tolerability of migraine control medications? What is the effectiveness, safety, and tolerability of specific migraine control medications compared with placebo, nonspecific medications, and nonpharmacologic treatments? The answers to both of these questions are not yet definitive and require an evaluation of the previous evidence to reach a conclusion.
1,3 Solutions
(1) In 1998, with funding from the Agency for Health Care Policy and Research (AHCPR), the Duke University Center for Health Care Decision and Research and the American Academy of Neurology jointly completed four treatment technology assessments for migraine based on the AHCPR’s health technology assessment methodology. These were: self-administered medications during migraine attacks [8], parenteral medications during migraine attacks [9], migraine prophylaxis medications [10], and behavioral/physical therapy for migraine [11]. Subsequently, the American Academy of Neurology funded the completion of a health technology assessment of isobarbital-containing medications and headache diagnostic techniques. (2) To provide clinicians with evidence-based guidelines for migraine and to improve the prognosis of migraine patients, based on the findings of the five health technology assessments mentioned above and based on standardized guideline development methods, the Headache Consortium formed by the American Academy of Neurology completed the guidelines and labeled the strength of each recommendation in the guidelines (cf. Table 1).
The strength of recommendation scale is based on multiple high-quality randomized controlled trials (RCTs) that are directly relevant to the recommendation and whose findings are consistent with each other; Level B is based on non-best evidence recommendations, such as a small number of RCTs with some variation in findings that are not directly relevant to the recommendation; and Level C is a consistent expert opinion of the Headache Consortium.
The evidence-based migraine guidelines address four major issues in the management of migraine: neuroimaging of migraine; pharmacological treatment of migraine attacks; pharmacological prevention of migraine; and non-pharmacological management of migraine.
2. Analysis of research evidence
The evidence of migraine prevention and treatment is from Level 1 clinical trials (refer to the trial classification in Table 2); there are no Level 1 diagnostic trials for migraine, and the evidence of migraine diagnostic techniques is from Level 2 or Level 3 trials; there is a lack of evidence on how to compare the efficacy of different drugs and how to choose a reasonable treatment plan for individual patients.
Level 1 clinical studies with a large sample of independent* consecutive patients with a suspected migraine diagnosis against the gold standard**. 2 clinical studies with a small sample of independent consecutive patients with a suspected migraine diagnosis against the gold standard**. 3 clinical studies with a large sample of independent non-consecutive patients with a suspected migraine diagnosis against the gold standard. 4 clinical studies that do not meet any of the above criteria Clinical studies that do not meet any of the above criteria
2.1 Neuroimaging of migraine
Migraine is a type of primary headache, and its diagnosis should not only exclude secondary headache, but also determine whether it is combined with other primary headaches, such as tension headache. Since neuroimaging is more reliable than any other tests in detecting the cause of secondary headache, neuroimaging can be performed to exclude secondary headache when there is difficulty in diagnosing primary migraine.
2. 1. 1 General principles of neuroimaging examination
1) Patients with headache who are not likely to have intracranial abnormalities and whose examination will not affect the treatment plan generally do not undergo neuroimaging. 2) The following patients need to consider neuroimaging: 1) rapid increase in headache frequency in a short period of time; 2) history of ataxia, local numbness and tingling, or other focal neurological signs; 3) previous history of painful awakening during sleep. 3) The absence of the above does not mean that there are no intracranial abnormalities or no Neuroimaging should be selected by the physician with specific circumstances, such as those who are anxious and depressed because of worrying about the consequences of headache, and those whose physicians suspect intracranial abnormalities can feasibly undergo neuroimaging to dispel the concerns of patients and physicians.
2. 1. 2 Recommendations of the Headache Consortium regarding neuroimaging of non-acute headache
1) For patients with unexplained abnormal neurological signs, neuroimaging is feasible to rule out secondary headache (Grade B); 2) For migraine patients without abnormal neurological signs, neuroimaging is generally not feasible (Grade B); 3) For atypical migraine and other atypical primary headaches, neuroimaging is feasible to rule out secondary headache (Grade C); 4) For patients with tension headache, neuroimaging is inconclusive. 5) The relative sensitivity of MRI and CT in evaluating migraine and other non-acute headaches is inconclusive (Class C).
2.2 Pharmacological treatment during migraine attacks
2,2,1 OverviewThe frequency of headache attacks, the duration of attacks and the degree of affectedness vary in different migraine patients, and can vary from attack to attack in the same patient. Therefore, the intensity of headache treatment should be consistent with the severity of the headache, i.e., the patient and his or her attacks should be graded in order to select different treatments (stratifiedcare, called graded treatment). Do not continue with medications that are ineffective as well as intolerable (stepcare, called step therapy). Preventive treatment should be given to patients who do not respond to medications during attacks, whose headache severely affects their quality of life, and who have frequent applications of medications for treatment of attacks.
2.2.2 Long-term treatment goals for migraine are to reduce the frequency, severity, and disabling nature of attacks; reduce the use of poorly tolerated, ineffective, or undesired attack medications; improve quality of life; avoid escalation of attack medications; improve the patient’s own ability to cope with migraine attacks; and reduce anxiety and other headache-derived psychiatric symptoms.
2.2.3 General rules for migraine treatment
1. Make a clear diagnosis; 2. Educate patients about the disease; 3. Set appropriate treatment goals and adjust patients’ expectations so that they can actively participate in treatment; 4. Develop a treatment plan and individualize treatment: according to the frequency, severity, and concomitant symptoms of headache in specific patients, the degree of impact of headache on patients, patients’ response and tolerance to specific medications, and patients’ comorbidities ( heart disease, pregnancy, uncontrolled hypertension), etc. to select the treatment plan; 5. Encourage patients to look for and avoid triggering factors.
2,2,4 Treatment during the exacerbation period
(1) Objective
To rapidly relieve headache and prevent recurrence; to restore patients’ ability to live normally; to reduce the use of standby and emergency medications; emergency medications are those that patients can take conveniently at home to relieve headache for which other treatments are ineffective; to enhance self-care and reduce the consumption of medical resources; to adopt an overall treatment plan with a good cost-effect ratio; and to reduce or avoid side effects.
(2) Principles
Treat patients with moderate to severe migraine and mild to moderate migraine with poor efficacy of non-specific medications with specific medications such as tretinoin and dihydroergotamine; patients with severe nausea and vomiting should be given non-oral medications with additional antiemetics; emergency medications should be available for severe migraine patients for whom other treatments are ineffective; prevent pharmacogenic headache; frequent use of ergotamine, opioids, tretinoin and other single The frequent use of ergotamine, opioids, tretinoin, and other single-component analgesics (barbiturates, caffeine, isooctenamides) is often thought to cause pharmacogenic headache, so most experts recommend: generally, only patients with headache ≥2 days per week should be treated with headache-onset medications, and prevention is recommended for frequent overuse of attack medications.
(3) Therapeutic drugs
①Specific drugs
A Tritan class (5-HT1b/1d receptor agonists): Naratriptan, Rizatriptan, sumatriptan and zolpidem are safe and effective, and are the drugs of choice for moderate to severe migraine attacks without contraindications (Class A); non-specific drugs with poor efficacy and migraine patients without contraindications can be preferred to this class (Class C); migraine patients with nausea and vomiting can be given sumatriptan intranasally/subcutaneously ( Class C).
B Ergot alkaloids: Dihydroergotimine (DHE) nasal spray is safe and effective and preferred for moderate to severe migraine attacks (Class A); DHE intramuscular/subcutaneous can be used for moderate to severe migraine attacks and (DHE + antiemetic) intravenous can be used for severe migraine attacks (Class B); DHE subcutaneous/intravenous/subcutaneous/transcutaneous can be used for migraine attacks with nausea and vomiting (Grade C); DHE subcutaneous/intramuscular/transanal administration can be used for any migraine patient with poor non-specific drug therapy (Grade C); ergotamine oral/transanal or combined with caffeine can treat some moderate-to-severe migraine attacks (Grade B).
②Non-specific drugs
A. Antiemetics: oral antiemetics are adjuvant drugs for migraine treatment (Grade C); gastrofacial intramuscular/transcatheter administration can be used alone to relieve headache (Grade B); methylphenidate can be used as an adjuvant drug for migraine attacks with nausea and vomiting (Grade C); methylphenidate intramuscular/transcatheter/transcatheter administration and chlorpromazine transcatheter administration can be used for some moderate to severe migraine attacks (Grade B); 5-HT3 receptor blockers alone are not effective for migraine attacks (Grade B). are ineffective for migraine attacks (Grade B), but can be used to control nausea and vomiting during migraine attacks (Grade C).
B Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs or their caffeine complexes taken orally are the first-line drugs for mild to moderate migraine attacks and severe migraine attacks with previous effective use (Grade A); acetaminophen can treat migraine attacks (Grade B); paracetamol alone should not be used to treat migraine attacks (Grade B); ketorolac intramuscular injection can be used for migraine attacks under medical supervision (Grade C).
C Pain relievers containing isobarbital: Because of addiction, withdrawal reaction and pharmacogenic headache, clinical use of these drugs should be restricted or under medical supervision (Grade B).
D opioid analgesics: parenteral opioids or oral opioid analgesics in combination with other drugs can treat migraine attacks without contraindications, such as bupropion nasal spray for migraine attacks (Class A); after weighing the risks of strong sedation and drug overuse, parenteral opioids can be used as emergency drugs for migraine attacks (Class B), such as bupropion as emergency drugs for migraine (Class C). Because of the widespread clinical use of bupropion, one must be alert to problems such as drug overdose and dependence.
E Other medications: isooctenamide alone or isooctenamide in combination with other medications can control mild to moderate migraine attacks (Grade B); corticosteroids (dexamethasone/hydrocortisone) can be used for migraine persistence (Grade C); there is currently insufficient evidence for the intranasal administration/static push of lidocaine for migraine attacks (Grade B).
2,3,1 Objectives
To reduce the frequency and severity of headache attacks and the duration of attacks; to enhance patient sensitivity to treatment during attacks; to improve function and reduce disability.
2.3.2 Indications for consideration of pharmacological prophylaxis
(1) those whose migraine still seriously affects the quality of life after the treatment of attack phase; (2) those who have frequent migraine attacks; (3) those who overuse or contraindicate the use of attack phase treatment drugs, and those whose attack phase treatment drugs are ineffective; (4) those who have large side effects of attack phase treatment; (5) the cost problem of treatment and prevention; (6) patient selection; (7) rare types of migraine: hemiplegic migraine, basal type migraine, migrainous cerebral infarction.
2,3,3 Principles
(1) Drug selection: Prefer drugs that are really effective; adhere to the principle of low-dose and incremental treatment; try each drug for 2 to 3 months to fully judge its clinical efficacy; avoid interference with medication (overuse of drugs for acute treatment); prefer long-acting agents.
(2) Efficacy evaluation: monitor the changes of headache by using headache diary, and reduce or stop the medication only after 3 to 6 months of complete relief of headache.
(3) Medication for comorbidities: Some comorbidities (stroke, heart attack, Raynaud’s phenomenon, epilepsy, mood disorders, anxiety, etc.) may be an opportunity for treatment and may also limit the choice of therapeutic drugs, which should be fully considered when selecting medication. The principles of medication selection for comorbidities are as follows: try to use medications that are effective for both migraine and comorbidities; do not use medications that are contraindicated for comorbidities; ensure that medications for comorbidities do not trigger/exacerbate migraine; pay attention to drug interactions; and try to use medications that have few side effects on the fetus for patients who are pregnant or about to become pregnant.
Table 6 Migraine prophylactic medication recommendations Group 1 Group 2 Group 3 Group 4 Group 5 Amitriptyline β-blockers:A :Antidepressants: dimethyl ergometrine vinblastine vinblastine dipropionate sodium aminoglutethimide aminoglutethimide carbamazepine insulin metoclopramide doxepin chlorpromazine hydrochloride thiamethoxazole naphthacrine fluvoxamine clonidine calcium channel blockers: promethazine colistin hydrochloride nimodipine or isoptin Mirtazepine Anti-inflammatory pain NSAIDs: Nortriptyline Nicardipine Aspirin Proxetine Heartburn Phenoxyphenylpropionic acid Protriptyline Heartadine Fluoxyphenylpropionic acid Sertraline Ketophenylpropionic acid Chloroperidone Meprobamate Venlafaxine Naproxen Other antidepressants: Naproxen sodium Cyproheptadine Ampicillin Thiodiazolone Gabapentin Isobutyrophenic acid Other drugs: Tolte FeverfewB : (drugs with side effects) Magnesium phenelzine
2,4 Non-pharmacological control
2.4.1 Non-pharmacological control principles
Non-pharmacological treatment includes behavioral therapy and physical therapy. Behavioral therapy includes relaxation therapy, biofeedback therapy, cognitive-behavioral therapy, and physical therapy includes acupuncture, neck exercises, exercise and other treatments. Most migraine patients want to try non-pharmacological treatment before regular medication, so the American Headache Coalition recommends that the following patients be considered for non-pharmacological management: (1) patient selection; (2) poor medication tolerance; (3) those with medication contraindications; (4) those with poor or ineffective medication; (5) those with impending pregnancy, pregnancy, and lactation; (6) those with frequent, excessive, or long-term use of pain relievers; ( (7) those with persistent headache-derived tension and anxiety.
2,4,2 Recommendations for non-pharmacological control
Behavioral/physical therapy is primarily used for headache prevention, not for alleviating symptoms during headache attacks, so it is often used clinically in combination with medications to prevent migraine recurrence. The American Headache Coalition recommends the following behavioral/physical treatments for migraine: (1) relaxation therapy, biofeedback therapy such as relaxation therapy heating/electricity, and cognitive-behavioral therapy are recommended for migraine recurrence prevention, but there is a lack of evidence on which method is better for specific patients (Level A); (2) combined medication and cognitive-behavioral therapy is better than medication alone (Level B); (3) hypnosis, acupuncture, maxillofacial therapy, and hyperbaric oxygen are currently recommended for migraine recurrence prevention. orthopedics, hyperbaric oxygen and other physical treatments for migraine prevention and treatment are insufficient evidence.
3. Conclusion
Evidence-based guidelines for migraine are recommendations regarding the role of neuroimaging in migraine and the effectiveness and safety of interventions, and the vast majority of these recommendations are well documented and convincing.
The American Headache Coalition states that the Migraine Evidence-Based Guidelines are part of the American Academy of Neurology’s Migraine Diagnosis and Treatment Educational Series and that their recommendations are based on a systematic evaluation of the available evidence. The guidelines do not exclude other reasonable interventions and treatment recommendations, nor do they exclude other scientific approaches to guideline development. Patient-specific treatment should be selected by both physicians and patients based on a combination of specific circumstances and guideline recommendations.
The statistical efficacy grading scale level criteria for drugs, definitely ineffective or harmful drug efficacy compared with placebo is not statistically different or not clinically significant +
+ statistically and clinically significant differences in the efficacy of the drug compared with placebo
Drug clinical efficacy grading scale level criteria ineffective: the majority of patients with no significant change in headache after the drug low efficacy: very few patients with significant improvement in headache after the drug moderate efficacy: some patients with significant improvement in headache after the drug high efficacy: the majority of patients with significant improvement in headache after the drug