Assessment and Treatment of Migraine Headaches

Educational Objectives

The goal of this program is to improve the diagnosis and management of migraine. After hearing and assimilating this program, the clinician will be better able to:

1. Identify the neural pathways that trigger migraine.
2. Recognize the importance of prevention and early treatment of migraine.
3. Distinguish among the various types of primary and secondary headaches.

Summary

Migraine: the main pain pathways originate from the trigeminal system; the primary trigeminal afferents are V1 (ophthalmic division), causing pain around the periorbital area and the forehead; pain can also arise from the upper cervical afferents; patients with migraine often report pain at the base of the skull and neck pain; pathways converge in the trigeminal complex in the brain stem; if pain continues, pain afferents transmit signals to the thalamus, the symptoms become more diffuse, and pain may become a chronic pattern; mainly involves vasoactive peptides, including calcitonin gene-related peptide (CGRP) and substance P, released from the nociceptive fibers

Diagnosis of migraine: classification of migraine guides treatment; according to the International Classification of Headache Disorders, migraine with aura need not be unilateral or accompanied by throbbing; it can be severe and become worse with activity (common in adolescents); only one accompanying symptom is required; chronic migraine requires an incidence of ≥15 headaches per month, with 8 being severe enough to meet migraine criteria or resolve with a triptan

Medication overuse: a common problem; triptans can be used ≤10 day/mo without causing rebound headache; anti-inflammatory medications (AIMs) can be taken ≤15 day/mo; prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) for milder migraines can prevent migraines from becoming chronic; combination medications and opioids are not recommended because they tend to make migraines more chronic; to treat medication overuse, the first step is to counsel and educate the patient; start with a preventive therapy and give appropriate abortive agents, usually a triptan and an AIM

Treatment of acute migraine: early intervention with prescribed medication is important; start with an AIM for mild headache; if headache does not improve or worsens, prescribed triptans may be taken 2 to 3 times weekly; formulation should be in accordance with the symptoms, ie, if vomiting occurs, a nasal spray or an injectable form of triptan is used; patients who need abortive agents 1 to 2 times weekly probably require a daily medication; for 50% of patients who take triptans, headache resolves in ≤2 hr; most preparations are oral; sumatriptan and zolmitriptan (better absorbed) are available in nasal form; naratriptan and frovatriptan are approved for menstrual migraine (onset is slower but effect lasts longer); sumatriptan is available in an injectable form (provides the fastest mode of action); if the patient has tried triptans with no improvement, ergotamines are an option; a nasal spray dihydroergotamine (DHE; eg, DHE 45) has recently been released; DHE mesylate (Migranal, Trudhesa) is also available as a nasal spray; an inpatient intravenous DHE protocol is available for migraines lasting weeks; NSAIDs with level A evidence include naproxen (eg, Aleve, Anaprox, Naprosyn), diclofenac (eg, Cambia [dissolvable form], Voltaren, Zipsor), and ibuprofen; nausea and vomiting can be disabling and affect absorption of as-needed medications; if nausea is persistent, antinausea medication may be needed; nerve block to abort migraine attack is an option for patients in the emergency department; rizatriptan is approved for children and adolescents aged ≥6 yr; other triptans are approved for ages >12 yr

Prevention of migraine: preventive therapy is recommended in patients with disabling migraine 4 to 6 day/mo, or 4 severe episodes; topiramate — less likely to cause cognitive issues at lower doses; start at 25 mg and increase weekly to 75 to 100 mg (sensitive patients may stay at 50 mg); does not affect birth control medication at doses <200 mg; zonisamide — consider in patients with mild cognitive impairment; divalproex sodium (Depakote) — rarely used because of associated weight gain and teratogenicity; gabapentin — has insufficient evidence for migraines but may be considered in low doses in patients with a cervicogenic component or in elderly patients with comorbidities; tricyclic antidepressants — eg, nortriptyline, amitriptyline; can be helpful; start with 10 mg nortriptyline and limit maximum dose to 30 mg, or 5 mg amitriptyline to maximum of 10 mg; consider in patients with sleep issues, anxiety, or neuropathic pain; selective serotonin reuptake inhibitors — not helpful for migraine and may worsen symptoms; serotonin and norepinephrine reuptake inhibitors — eg, venlafaxine (Effexor), duloxetine (Cymbalta, Drizalma Sprinkle, Irenka); can be helpful; duloxetine is easier to titrate; β-blockers — the speaker tends to use more selective agents (eg, atenolol); however, the blood pressure range in younger patients is lower and the drug is less tolerated; such patients may also have Raynaud disease and asthma; calcium channel blockers and other antihypertensive agents — have few side effects and some supportive evidence

Nonpharmacologic interventions: cognitive behavioral therapy and biofeedback relaxation — beneficial in patients with anxiety; it is important to address insomnia; lifestyle modifications — recommended; depression, anxiety, Raynaud disease, fibromyalgia, and irritable bowel syndrome are commonly associated with migraines

Management of migraine: use of CGRP monoclonal antibodies (mAb) is beneficial, especially in patients in whom other medications are not well tolerated or helpful; CGRP is a potent cerebral artery vasodilator; studies have found no cardiovascular issues with use of CGRP antagonists; mAbs are very large, do not cross the blood-brain barrier, are not eliminated by the liver or kidney, and have minimal drug-drug interactions; erenumab is a fully humanized mAb that demonstrates efficacy and safety in migraine episode prevention; erenumab, galcanezumab, and fremanezumab are available in subcutaneous form for monthly self-administration; 50% to 74% of patients have >50% reduction in headache days and decreased prodromal symptoms on nonheadache days; these agents can cause hypertension early in treatment (monitor blood pressure weekly for the first few months)

Small-molecule CGRP receptor antagonists: ubrogepant and rimegepant have been approved by the US Food and Drug Administration as abortive medications; rimegepant is also approved for every-other-day use as a preventive therapy; atogepant is approved for daily use; these drugs interact with cytochrome P450 3A4, have a broader safety profile, and can be considered in people with vascular risk factors

Other options: lasmiditan — a 5-HT_1F agonist; has no cardiovascular side effects but causes drowsiness, impaired driving, and dizziness; there is risk for medication overuse; celecoxib (Celebrex, Elyxyb) oral solution — now available; acupuncture — worth trying in patients who do not want to use medication; neuromodulation — various devices are available; there is little evidence to support efficacy, and devices are expensive, but it is an option

Primary headache disorder: seen following viral infections and vaccines, primarily in patients who have a history of migraine; findings in studies suggest treating this as migraine; usually abates over time

Cluster headache: a side-locked headache; wakes the patient at night; more common in men; lasts for a long period of time; other headaches in the trigeminal autonomic category are much shorter in duration; standard abortive therapy is to administer sumatriptan (eg, Imitrex, Sumavel DosePro, Zembrace SymTouch) injections; patients are given steroids followed by an occipital nerve block; 80 mg verapamil has beneficial results; if there is a cardiac history, electrocardiography is performed, and the dose is modulated; galcanezumab (Emgality), a CGRP mAb, is effective but requires prior authorization

Secondary headaches: for sudden-onset headache, consider hemorrhage and arterial dissection; thunderclap headaches (TCH) are severe and occur suddenly; subarachnoid hemorrhage (SH) — occurs more often in patients with migraine; patients with migraine who present with headache of a different character than normal should undergo imaging; usually presents with TCH; most SH are the result of saccular aneurysms; imaging should be performed within 3 day because it may normalize if delayed; reversible cerebral vasoconstriction syndrome — a reversible vasculopathy; onset of headache is sudden; neurologic deficits and seizures may be present; TCH is usually the primary symptom and may be recurrent; initial imaging may be normal; TCH — commonly caused by medications; obtain a toxicology screen

Sagittal sinus thrombosis: headache is a presenting feature; papilledema may be present; often hemorrhagic as a result of venous occlusion; requires anticoagulant therapy

Considerations for migraine: patients should keep a migraine diary to record frequency, intensity, and triggers of headache; recommend lifestyle modifications, adequate sleep, and preventive medication as necessary; patients with chronic migraine or new-onset migraine with no focal neurologic symptoms do not require imaging; if imaging is performed, magnetic resonance imaging is more helpful than computed tomography; an individualized treatment plan is recommended; treat associated comorbidities; advise patients to have realistic expectations about the timeline and the need to try different medications

Readings

Altamura C, Corbelli I, de Tommaso M, et al. Pathophysiological bases of comorbidity in migraine. Frontiers in Human Neuroscience. 2021;15. doi:10.3389/fnhum.2021.640574; Andreou AP, Fuccaro M, Lambru G. The role of erenumab in the treatment of migraine. Therapeutic Advances in Neurological Disorders. 2020;13. doi:10.1177/1756286420927119; Ashina M, Hansen JM, Do TP, et al. Migraine and the trigeminovascular system — 40 years and counting. The Lancet Neurology. 2019;18(8):795-804. doi:10.1016/s1474-4422(19)30185-1; Begasse de Dhaem O, Robbins MS. Cognitive impairment in primary and secondary headache disorders. Current Pain and Headache Reports. Published online March 3, 2022. doi:10.1007/s11916-022-01039-5; dos Santos JBR, da Silva MRR. Small molecule CGRP receptor antagonists for the preventive treatment of migraine: A review. European Journal of Pharmacology. 2022;922:174902. doi:10.1016/j.ejphar.2022.174902; Johnston MM, Rapoport AM. Triptans for the management of migraine. Drugs. 2010;70(12):1505-1518. doi:10.2165/11537990-000000000-00000; Levinsky Y, Eidlitz-Markus T. Thunderclap headache in children and adolescents. Current Pain and Headache Reports. 2022;26(3):235-239. doi:10.1007/s11916-022-01020-2; Ong JJY, Wei DYT, Goadsby PJ. Recent advances in pharmacotherapy for migraine prevention: From pathophysiology to new drugs. Drugs. 2018;78(4):411-437. doi:10.1007/s40265-018-0865-y; Prasad S, Mehadi A, Kaka N, et al. Diagnostic protocols and newer treatment modalities for cluster headache. Disease-a-Month. Published online January 6, 2022:101316. doi:10.1016/j.disamonth.2021.101316; Schwedt TJ. Preventive therapy of migraine. CONTINUUM: Lifelong Learning in Neurology. 2018;24(4):1052-1065. doi:10.1212/con.0000000000000635; Vargas BB. Acute treatment of migraine. CONTINUUM: Lifelong Learning in Neurology. 2018;24(4):1032-1051. doi:10.1212/con.0000000000000639.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Knepper was recorded at the 2022 Update in Internal Medicine, Advances Changing Practice, held on October 6-7, 2022, in Pittsburgh, PA, and presented by the University of Pittsburgh School of Medicine. For information about CME activities from this presenter, please visit https://meded.dom.pitt.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

OP611802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.