Migraine Prophylaxis and Treatment Duren Michael Ready, MD, FAHS Baylor Scott & White, Temple, TX DMReady@tamhsc.edu
Disclosure • Dr. Ready has disclosed that he is on the speaker’s bureau for Allergan, Amgen, Biohaven, Lilly, and Teva, and he is on the advisory board for Theranica.
Objectives By the end of this educational activity, the learner should be better able to: 1. Increase awareness and interest of headache in Primary Care 2. Provide a clinical framework for the diagnosis, prophylaxis, and acute migraine treatment 3. Identify risk factors for migraine progression and develop a plan for treatment using migraine staging
Why Should I Care?
First Things First Primary or Secondary Headache • Primary – nervous system you are born with or acquire (trauma) & the environment you are in • Migraine, Cluster, Tension Type • Headache as the Condition • Secondary – headaches that are caused by something else • Infection, Mass, Vascular, Trauma • Headache as a Symptom 6
SNOOP4 Ruling Out Secondary Headaches S ystemic symptoms and signs Infectious N eurologic symptoms or signs Neoplasm O nset: peak at onset or <1 minute Vascular O lder: after age 50 years Temporal Arteritis P ostural, positional aggravation CSF Leak P recipitated by valsalva, exertion, etc. Mass / CSF Leak P apilledema ↑ CSF Pressure Silberstein SD, Lipton RB. In: Silberstein SD et al, eds. P revious headache: pattern change Above Wolff’s Headache and Other Head Pain. 8th ed. New York: Oxford University Press; 2008:315‐377. Dodick D. N Engl J Med. 2006;354:158‐165. Bigal ME et al . J Headache Pain . 2007;8:263‐272. 7
Headache Imaging Indications — ACR Guidelines Clinical Features/Red Flags Suspected Condition Recommended Imaging* Associated with trauma Bleed CT head without contrast Neoplasm, vascular New feature or neurologic deficit MRI brain malformation, aneurysm CT head without contrast; MRI brain, MRA head Thunderclap (sudden onset; severe) Bleed (esp. SAH) and neck, MR venogram head (if CT negative) Sudden unilateral, and/or pain radiating Vascular (e.g., arterial CTA head and neck; to the neck dissection) MRA head and neck Pain due to trigeminal autonomic Neoplasm MRI brain with/without gadolinium cephalgia Persistent or positional pain CSF leak/IIH MRI brain with/without gadolinium Immunocompromised state Infection; malignancy MRI brain with/without gadolinium Temporal pain in older individuals Giant cell arteritis MRI brain *Additional imaging may be recommended based on initial findings. ACR=American College of Radiology; CT=computed tomography; MRI=magnetic resonance imaging; SAH=subarachnoid hemorrhage; IIH=idiopathic intracranial hypertension. Douglas AC et al. J Am Coll Radiol. 2014;11:657‐667.
Migraine: More Than a Headache • Tension Type HA & Migraine 2 nd & 3 rd most prevalent medical disorder worldwide • Migraine accounts 30% of global burden of disability & 50% of all Neuro disability • 4 th leading cause of disability in women & 7 th overall Lancet 2012 9
Why Migraine? Why Should I Care? • 6% ♂ , 18% ♀ , 33‐37% reproductive ♀ , 4% CDH • Returning armed forces 38% ♂ , 58% ♀ , 20% CDH • Most common 25 – 55yr (most productive years) Couch JC, et al. Headache . 2003;43:570-571. Lipton et al. Headache 2001. 10
Battle of the Migraine Screens ID Migraine™ (PIN) P.O.U.N.D. P ulsatile quality 1. Does light bother you when you have a headache? ( P hotophobia) Duration 4–72 h O urs 2. Has a headache limited your U nilateral location activities for a day or more in the last N ausea or vomiting three months? ( I mpairment) 3. Are you N auseated or sick to your D isabling intensity stomach when you have a headache? Number of Features Probability of Migraine 1–2 17% Positive result: ≥2 “yes” responses 3 64% PPV: 93% 4–5 92% PPV=positive predictive value. Lipton RB et al. Neurology . 2003;61:375‐382; Lipton RB et al. Headache . 2004;44:387‐398; Detsky ME et al. JAMA. 2006;296:1274‐1283; Ebell MH. Am Fam Physician. 2006;74:2087‐2088.
Migraine – Most Common Episodic Headache in Primary Care Multisite, prospective Landmark Study of adults consulting their physician (93% primary care) with episodic headache • IHS diagnosis based on diary review (n=377) Migraine or Probable Migraine Tension‐Type Unclassifiable 94% 3% 3% Tepper SJ et al. Headache. 2004;44:856‐864.
Migraine Treatment Target: 5HT & CGRP Receptors Triptans & ergots prevent CGRP release and constrict CGRP‐dilated vessels; Lasmiditan prevents CGRP release OnabotulinumtoxinA prevents CGRP release Anti‐CGRP ligand MABs: Anti‐CGRP fremanezumab, galcanezumab, receptor eptinezumab MAB: 5‐HT 1F erenumab CGRP receptor antagonists (gepants): Ubrogepant, Rimegepant, Atogepant, Vazegepant Edvinsson L et al. Nat Rev Neurol . 2018;14:338-350. Slide courtesy of Stew Tepper, MD Lars Edvinsson MD, PhD
CGRP and Migraine • CGRP levels are increased during migraine • CGRP infusions can trigger migraine • CGRP inhibitors block migraine progression • Reduces migraine frequency, intensity, duration • CRRP inhibition allows brain to recover more fully from a migraine event • A brain which has not fully recovered from a migraine attack is more reactive. Leaving it more vulnerable for a subsequent attack. Pain . 2003;106:461–47
Staging Migraine • Developed by Lipton, Cady, Farmer, & Bigal • 1 st doctor/patient book • Based on Migraine frequency not severity • http://www.managingmigraine.org/online‐ books/patient/flash.html 16
Migraine Stages Stage 1 – Infrequent Episodic Education plus effective acute treatment ≤ 1 Migraine/month Stage 2 – Frequent Episodic Education plus effective acute treatment with back up; medications limits; preventive measures 2 – 6 headache days/month Stage 3 – Transforming Migraine Education; preventive pharmacology; acute pharmacology with back up & rescue; behavioral 7 – 14 headache days/month interventions Stage 4 – Chronic Migraine Education; preventive pharmacology; judicious acute pharmacology with back up and rescue; behavioral - ≥ 15 headache days/month interventions
Migraine Frequency 50% 39.3% 40% 30% 2.5% progress per year 22.5% 20% 14.0% 26% revert / 2 years 8.4% 10% 3.9% 1.8% 1.5% 1.4% 1.0% 0.7% 0.6% 0% 0‐1 2‐3 4‐6 7‐9 10‐11 12‐14 15‐18 19‐21 22‐24 25‐27 28‐31 Headache, days/month 1. Lipton RB. Neurology. 2009;72(5 suppl):S3‐S7. 2. Manack A et al. Neurology . 2011;76(8):711‐718. 3. Blumenfeld AM et al. Headache . 2013;53(4):644‐655. 4. Bigal ME et al. Headache. 2008;48:1157‐1168.
Headache Treatments Abortive – Pain freedom in 2 hours Preventive – Reduce frequency, intensity and improve response to acute meds Rescue – When the stop medicine didn’t 19
Migraine Outcomes: Acute therapy vs. No Acute Therapy J Headache Pain . 2012;13:121‐7
Acute Therapy • Goal is pain freedom in 2 hours • Treat at mild pain (prior to central sensitization) • May use polypharmacy 21
Triptan Pearl: Treat @ Mild Pain Early Intervention Improve Efficacy 2 Hour Pain Free Response 80% 80% 60% 58% 40% 35% 20% 0% Mild Moderate Severe Pain Intensity When HA Treated Cady RK, et al. Headache 38:173-83; Pascual J, et al. Headache 42[supl 1]:S10-S17
Acute Oral Therapies Non‐triptan • NSAIDS • Combinations • APAP/ASA/caffeine There is no medication that is • Analgesics perfect for all migraine attacks • Antiemetics or all circumstances in which Triptans / Ergotamines treatment is needed. Ditans / Gepants When to consider • First‐line therapy • Adjunctive therapies 23
Triptans: What’s the Difference? Triptan T 1/2 $ Pearl 2.5h 9/$12 Multiple formulation Sumatriptan 2‐3h 9/$16 Reduce dosed with propranolol Rizatriptan Typically better response Eletriptan 4h 9/$37 3h 12/$126 Good tolerability Almotriptan 3h 6/$38 Best tolerated NS Zolmitriptan Scheduled dosing for Menstrual Related Migraine Naratriptan 26h 9/$26 6h 9/$160 Scheduled dosing for Menstrual Related Migraine Frovatriptan
Migraine Recurrence Early GI Symptoms Long Duration Migraine Augment with antiemetic Polypharmacy Metoclopramide NSAID/Antiemetic Prochlorperazine Long ½ life Nara/Frova Bypass Gut Scheduled Dosing IN spray or powder Injectable Choosing Triptans Failure to one doesn’t predict response to other Use over at least 3 attacks Rapid Onset of Pain Limit to 10 days/ Month Triptan Nonresponder Fast acting PO Ele/Riza/Zolmi Start Migraine Preventive Bypass gut Use Max dosage IN – Suma liquid /powder Alternate triptan/formulation Subcut Suma Polypharmacy Antiemetic PO / PR
Stratified Care Low NSAIDs Disability Disability Moderate NSAIDs + neuroleptics Disability or triptans High or Severe Triptans Disability Parental Gpant/Dtans 26
New Kids on the Block Dtans & G‐pants Dtans Gepants • 5HT 1F receptor antagonist • CGRP receptor blockers • No vasoconstriction • No vasoconstriction • Lasmiditan • Ubrogepant / Rimegepant • Schedule V • Eight‐hour post dosing driving restriction • May take early or late
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