Commentary
Article
Author(s):
Migraine is a chronic neurological disease characterized by throbbing or pulsating unilateral or bilateral headache that can last from hours to days.
Introduction
Among the primary headache types, migraine remains one of the most severe and debilitating types, especially in women and those under the age of 50. Migraine is a chronic neurological disease characterized by throbbing or pulsating unilateral or bilateral headache that can last from hours to days. Migraine headaches can also be associated with additional symptoms including nausea and vomiting, photophobia, and phonophobia.1-4 Migraine headaches are a major financial burden with direct and indirect health care costs affecting patients, families, and employers.5-7
Pathophysiology
Migraine pathophysiology is complex, and although many theories have been suggested, most recent evidence involves the trigeminovascular system.8 Migraines can be triggered by many factors including stress, hormonal changes, foods, weather changes, odors, medications, and more (Table 19-13).9-13 When a migraine is triggered, the trigeminal nerve is activated and proinflammatory neuropeptides are released. Among these is calcitonin-gene related peptide (CGRP) and other neurotransmitters that cause vasodilation and inflammation, resulting in activation of pain sensing neurons and a hypersensitive pain environment.12-16
Clinical Presentation
The clinical presentation of migraine is heterogeneous, although it is described as having 4 major phases. Patients may not experience each phase, and in some cases may present atypically. The common phases described include the premonitory, aura, headache, and postdrome phases and are described in figure 1.1,13 The premonitory phase usually occurs 1 to 2 days prior to the aura and headache phase, with features that include fatigue, irritability, and food cravings. This phase is followed by the aura phase in some patients, which may include visual disturbances, sensitivity to light, and other features. The subsequent headache follows and is typically a pulsatile unilateral pain, often accompanied by nausea, vomiting, photophobia, and phonophobia. The final phase, called the postdrome phase, is the period post-headache and includes lethargy and fatigue.1,17-19
Other primary headache discussions are beyond the scope of this article, but include cluster headache and its variants, tension headaches, and numerous other types classified by the Headache Classification Committee of the International Headache Society (IHS).1 The most recent headache classification system published by the International Headache classification Society (IHCS) defines the major categories of migraine as those with and without aura and, in addition, defines migraine as chronic if it presents ≥15 days per month and episodic if ≤15 days per month.1,20,21
The diagnosis of migraine requires a referral to a primary care practitioner or neurologist, especially if patients present with mimicking conditions and/or “red flag” or “alarm” symptoms (Table 222-25). The “red flags” listed in Table 2 can be helpful during these initial encounters, offering guidance to the pharmacist during the screening for potential serious events requiring a referral to a medical practitioner or emergency care.22-25
The community pharmacist on the front lines of health care is easily accessible to patients with migraines. Pharmacists can play an important triage role when approached by patients with headaches in their pharmacies or noticing patients in the OTC analgesic section that appear to be looking for medications. All pharmacy staff may assist with this observation by notifying the pharmacist on duty regarding patients that appear to be or who ask about analgesics.26-29 To assist the pharmacist in this process, numerous screening tools are available which have a high sensitivity for diagnosing migraine (Table 330-36). These tools vary from short interview questions, such as in the ID Migraine Screener, to more extensive evaluations of how migraine may be affecting a patient’s quality of life, such as the Migraine Disability Assessment Scale (MIDAS). These screening tools and questionnaires can not only gauge migraine severity but also provide information to share with other members of the patients’ health care team, offering an intradisciplinary approach to care. In addition, the pharmacist can monitor the patient during their follow-up visits to the pharmacy.30-36
After an initial interaction with a patient who has headaches, including reviewing their history and/or conducting a screening test, the community pharmacist can make some recommendations for care.37-39 Patients who describe mild to moderate migraine symptoms may benefit from numerous non-pharmacological interventions and recommendations (Table 436-63,65-72) including lifestyle changes and improving sleep, diet, and stress levels. Other interventions may include recommending dark quiet environments, cold packs, and numerous neuromodulation (NM) devices, which are reviewed in Table 5.47-63 These NM devices work in a variety of ways to interfere with nerves involved with pain transmission processes, which propagate migraine pain and other symptoms.47-63
Patients with migraine should also be encouraged to keep a detailed diary that tracts migraine attacks, triggers, symptoms, severity, timing, length of attack, frequency, and response to treatments. Numerous mobile apps are available to utilize for a diary, including Migraine Buddy, Curelator NI-Headache, iHeadache, Migraine Diary, and others.64
Although there are not universal diets designed for migraine, certain diets may be beneficial. The brain is always working and needs protection from stress, particularly cellular and oxidative stress. Foods that are brain healthy include salmon; tuna; nuts; berries; and green leafy vegetables like broccoli, kale, and cauliflower. Processed food is reported to cause inflammation, so avoiding it is in the best interest of these patients. The popular Mediterranean diet is a great option due to its abundance of anti-inflammatory foods, good carbohydrates and fats, and olive oil, all of which are brain healthy. Limiting sugar may also be helpful to avoid the rise in insulin, which triggers inflammation. Food triggers should be a component of the patient's migraine diary as mentioned above.65-72
Medication Therapy
Migraine therapy is evolving, and newer medications are available that may provide patients with improved response and tolerability. The majority of migraine pharmacotherapies require prescriptions and pharmacists can use their clinical knowledge about the role of these agents to have discussions with patients and make recommendations to their providers. The community pharmacist is in a prime position to work with migraine patients and their providers to optimize therapies, improve quality of life, and minimize health care costs. Their initial involvement should be questioning patients regarding their headaches, utilizing simple screening tools, and discussing present or previous therapies. Providers with busy practices may appreciate input on the management of migraine in their patients. Discussions may include newer options for treatment, third party coverage, patient assistance, monitoring, and follow-up plans. Migraine treatment involves acute therapies (see Table 621,24,28,29,71,74,75–78,83,85,86,90,94,95) and preventive therapies (see Table 71,72-75,83,84,92), and the role of each will depend on individual patient responses. Although not a cure, medications and their combinations can have a significant impact on migraine symptoms and quality of life. The general goal for abortive therapies is taking them as early as possible, such as during the premonitory phase, and achieving pain relief or freedom within 2 hours.71-92 Key points are avoiding medication overuse headache.79,80
Acute management of mild to moderate migraine includes OTC agents such as simple analgesics and their combinations, along with non-steroidal anti-inflammatory drugs (NSAIDs). The pharmacist can offer guidance on dosing, restrictions on frequency of use, and follow-up on efficacy.81,82,91
Patients with moderate to severe migraines will usually require prescription therapies such as triptans (Table 871,75,76-79,83), gepants, others. Depending on migraine frequency, patients may require preventive management, as well, with options outlined in Table 8. Guidelines on when to prescribe preventives are published in detail by the American Headache Society, but in general it is based on migraine days per month and influence on quality of life.57,71,72 The migraine patient is best managed with a multimodal approach, using various lifestyle and non-pharmacological interventions, along with the layering or combinations of various pharmacotherapies. Comorbidities associated with migraine may allow overlap of treatment options, although this may also be associated with drug interactions, providing an additional monitoring opportunity for pharmacists.71-80 The routine use of opiates or barbiturate-containing compounds should be avoided because they are less effective than conventional treatments and associated with addiction and medication overuse headache.71,72,83-86
Because a majority of patients with migraines are women of childbearing years, pharmacists should be aware of how to initiate migraine abortive recommendations in these patients. Fortunately, the rise of estradiol in pregnancy results in many pregnant migraine patients experiencing less frequent and reduced severity of attacks. If treatment is required, a discussion with provider, patient, and pharmacist is warranted with shared decision-making. Recommendations include acetaminophen and/or a combination of acetaminophen with caffeine, with a limit of 200 mg daily of caffeine. The use of NSAIDs in severe attacks should be limited to the second trimester due to potential fetal effects. In the emergency department settings, intravenous metoclopramide alone or in combination with diphenhydramine may be useful for headache pain and associated nausea. Secondary options include corticosteroids (e.g., prednisolone), intravenous sumatriptan, or magnesium.
There are limited data to recommend lasmiditan or gepants for the abortive therapy of migraine in pregnancy. Similar to abortive treatment, there is limited evidence for the use of preventive migraine medication during pregnancy and a discussion with the patient and provider should occur to consider preventive options. A general recommendation is for patients to discontinue their preventive migraine medications via taper during pregnancy. If treatment is necessary, some options may include calcium channel blockers (e.g., amlodipine, nifedipine, verapamil) or antihistamines (e.g., cyproheptadine, diphenhydramine). The risk-benefit ratio should be considered for using traditional oral therapies in pregnant migraine patients (e.g., beta-blockers). Avoidence of antiseizure medications (e.g., topiramate and valproic acid), antidepressants (e.g., venlafaxine and amitriptyline), and the CGRP monoclonal antibodies and antagonists is recommended.72-75,87,88
Over the last 5 to 6 years, newly approved therapies have offered patients more options for both abortive and preventive care of their migraines. These agents provide an excellent opportunity for pharmacists to further engage patient care by educating patients on their role in therapy. These agents involve new delivery options, requiring patient education on proper use of self-injectables, new nasal and oral dosage delivery systems, along with assistance on third party payment challenges.1,58,83,84,90-94
Medication Overuse Headache
When certain medications are used more than the recommended frequency, a tolerance may develop to the medications and the severity and frequency of their headaches may increase. Certain drugs that may be problematic if overused include combination pain relievers containing barbiturates or opioids, triptans, ergotamines, combination analgesics containing caffeine, aspirin, acetaminophen, and NSAIDs. Patients that consume more than 200 mg of caffeine daily are also at an increased risk of medication overuse headache. Community pharmacists are in a prime position to monitor a patient’s use of analgesics.79,80,85
Conclusion
Migraine headaches remain a debilitating condition, management has improved with evolving therapies. Pharmacists’ role in the community setting provides the ideal position to help migraine patients. A community pharmacist can identify the migraine headache and recommend OTC medication while educating patients on medication overuse headache that could worsen their condition. Not only can a pharmacist educate a patient on administration and adverse effects of a medication, but they may also use screening tools and questionnaires to assess a patient’s migraine severity and quality of life. Additionally, pharmacists should be aware of alarm symptoms associated with headaches that may require more immediate attention. A pharmacist’s role in the health care team is invaluable as they are easily accessible and available to follow up with a patient. Patients can trust their pharmacist to educate them and suggest non-pharmacological therapies, as well as to ease concerns or fears they may have about starting new therapies. Pharmacists are knowledgeable, well-equipped, and available to the patient suffering from migraines and remain a first-line source when a patient is looking for therapy, referrals, and education regarding their migraine treatment.39,81,82,95