Managing Migraine: Primary Care for Primary Headaches

Transcription

1 Emerging Challenges in Primary Care: 2018 Managing Migraine: Primary Care for Primary Headaches Faculty Jeff Unger, MD, FAAFP, FACE Assistant Clinical Professor of Family Medicine, UC Riverside School of Medicine Director, Unger Concierge Primary Care Medical Group Rancho Cucamonga, CA 2 Disclosures Jeff Unger, MD, FAAFP, FACE has no financial relationships to disclose. 3 1

2 Learning Objectives 1. Utilize evidence-based strategies to diagnose patients presenting with headache 2. Identify associated conditions (e.g. depression), and red flags for potentially life threatening causes of headache 3. Use evidence-based recommendations to prescribe treatment for patients presenting with acute or emergent headache pain 4. Develop collaborate management plans, emphasizing patient education on avoiding triggers that cause headache, and adherence to prescribed treatment strategies 5. Discuss newer pharmacologic targets for managing patients with Chronic Migraine 4 PRE-TEST QUESTIONS 5 Pre-test ARS Question 1 How confident are you in your ability to treat patients with chronic migraine? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 6 2

3 Pre-test ARS Question 2 How often do you consider a diagnosis of migraine in a patient presenting with a chief complaint of headache? 1. Never 2. Rarely 3. Sometimes 4. Often 5. Always 7 Pre-test ARS Question 3 Intravenous infusion of CGRP into an asymptomatic patient with migraine will result in which of the following events: 1. Hypotension 2. Syncope 3. Acute migraine 4. Cardiac arrhythmia 8 Migraine Fact Check Prevalence of any form of headache was 93% in men and 99% in women Among men, 8% had, at some point, experienced migraine compared with 25% of women. Migraine is one of the world s 10 th leading cause of disability Migraine is a leading cause of ED visits in the US < 13 % of all migraineurs receive prophylactic treatment Migraine is considered a longterm, chronic disease Rasmussen BK. Epidemiology of headache in a general population- a prevalence study. JClinEpidemiol. 1991: 44 (11): Dodick, Et al. Headache

4 Primary and Secondary Headaches Primary: Migraine Cluster Tension-type Secondary: Traumatic Vascular Infectious Metabolic Oncologic Primary Secondary Inflammatory 10 Primary And Secondary Headache Disorders Primary H/A is idiopathic No identifiable cause No specific diagnostic tests Defined clinically Dx based on ruling out specific pathologic events Secondary H/A is a symptom reflective of underlying pathology Diagnostic tests useful Diagnosis based on defining pathology 11 Diagnostic Red Flags and Comfort Signs First or worst Abrupt onset Red Flags: Fundamental change in pattern New headache onset in patients < 5 or > 50 years of age Cancer, HIV, pregnancy Neurological dysfunction + headache HA onset with seizure or syncope HA onset with exertion, sex or Valsalva Abnormal vital signs In children, HA get progressively worse over time Ravishankar K. Which headaches to investigate. When and How. Headache Nov;56(10): Comfort signs: Stable pattern x 6 months Long history of same headaches In children-recurring, INTERMITTENT Normal neurologic exam Occur with menstruation +FH of same Known consistent triggers 12 4

5 Headache Time Course 13 Migraine Prevalence: Age and Gender Migraine prevalence peaks in the age range Adapted from Lipton RB, et al. Neurology. 2007;68(5): A stable pattern of recurrent disabling headaches without evidence of underlying cause. Definition of Migraine Migraineurs have a genetic sensitivity towards severe, disabling headaches. Migraineurs are born with a very sensitive nervous system The goal of migraine management is to allow the migraineur to learn to reduce their neurological sensitivity Migraine events disrupt normal neurologic brain function which increases the likelihood of having additional events 15 Unger J. Migraine prophylaxis. The Pain Practitioner. 17 (1)

6 Migraineurs Are Born With A Genetically Predisposed Sensitive Neurological System Triggers: Stress Hormonal changes Skipping meals Specific food (cheap red wine, caffeine) Sleep disruptions Medications and med overuse Weather Protective factors: Standardized sleep patterns Regular meals Exercise Stress management Pro-active treatment for menstrual migraine and prodromes Post menopause treatment Avoidance of triggers Reduction caffeine usage Minor head trauma Phases of a Migraine Attack Migraine Intensity Pre-HA Prodrome Aura 20 % Focal Migraine symptoms neurological occurring hours/days symptoms prior preceding to headache headache (<1 hour) Symptoms: Flashing lights Symptoms : or wavy lines Food cravings Numbness Mood changes Tingling in face Yawning Disturbed Fatigue senses Mild Migraine when headache is mild Symptoms: Sensitivity to light Sensitivity to sound Nausea Pain in the back of the head and neck Loss of cognition Headache Time (4 hours 5 days) Moderate to Severe Migraine when headache is moderate to severe Symptoms: Same as mild but more intense Can develop allodynia within 2-4 hours Post-HA Postdrome Migraine symptoms occurring hours/days after headache resolution Symptoms: Tiredness Confusion Dizzy Lowered appetite Stiff or sore muscles Adapted from Cady RK. Headache. 2008;48(9): Prodrome: Symptoms Irritability- 48 % Nausea-43 % Muscle pain/tenderness-38 % Change in energy level- 30 % Change in mood- 24 % Change in appetite-21 % Yawning-21 % 18 Luciani R, et al. Cephalgia 2000; 20:

7 Migraine: Spreading Cortical Depression and Aura 19 Patient Describing Aura 20 Neck Pain During Migraine Prevalence 75% of subjects Descriptions 69% - tightness 17% - stiffness 5% - throbbing 5% - other 82% had previously been given a diagnosis of tension-type headache Kaniecki R. Neurology. 2002;58(Suppl 6):S15-S

8 Cutaneous allodynia Hair hurts Painful when: Shaving Combing hair Touching scalp Resting head on pillow Pulling hair back (wearing a ponytail) Wearing eyeglasses or contact lenses Wearing hat or head band Even My Hair Hurts (allodynia) 22 Chen N, et al. Pain Med Jun;16(6): Genetic predisposition Migraine Pathogenesis Triggers evoke abberant firing of neurons resulting in cortical spreading depression (CSD) CSD activates the release of neurokinins and CGRP causing vascular dilation and increased platelet adhesiveness. Neuronal flow into the nucleus caudalis can eventually cause nausea, vomiting, dizziness, and severe head pain Hadjikhani N, Sanchez Del Rio M, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA. 2001;98(8): Video courtesy of American Headache Society. With Permission. 23 Diagnosis Of Migraine (ID Migraine) During the last 3 months, did you have the following with your headaches? 1. You felt nauseated or sick to your stomach Yes No 2. Light bothered you (a lot more than when you don t have headaches) Yes No 3. Your headaches limited your ability to work, study, or do what you needed to do? Yes Lipton RB, et al. Neurology. 2003;61: No 2/3 for migraine Sensitivity: 0.81 Specificity:

9 Barriers and Pitfalls In Primary Headache Diagnosis Headaches evaluated within Primary Care are rarely due to secondary causes. Remember, migraine is a neurologic event, not a pathologic process based upon vasodilation and constriction. Be cautious of patient directed diagnoses: Sinus, stress or allergic headaches. Most patients will have tried OTC meds prior to seeking professional consultation. Sinus headaches and neck pain think migraine. 25 Vital signs! Physical Exam Look for any focal neurological findings Listen to the head! Feel the scalp and neck muscles 26 Listen to the Head! 27 9

10 Headache Lab Tests CBC ESR T4, TSH, Thyroid Peroxidase Antibody Unger Jeff, Cady Roger K, Farmer-Cady Kathleen. Migraine Headaches, Part 1: Presentation and Diagnosis. The Female Patient. May 2003: Vol Heather History Recurrent disabling headaches Light Sensitivity Nausea Vomiting + Family History Lasts 4-72 hours 29 Diagnostic Evaluation Headache NO Primary Headache Atypical Features Danger signs present? Investigations YES Secondary Headache 30 Adapted from Silberstein et al. (eds.) Headache in Clinical Practice

11 Primary Vs. Secondary Headache Disorders 31 Imaging Patients With Migraine: The Yield Adapted from Frishberg BM, et al. Accessed Is This Migraine? -45 y/o man with nightly headaches x 2 weeks. Pain so severe he extracted his own teeth! 33 11

12 Cluster Headache: AKA Suicide Headaches Usually no aura Peak pain in 10 to 15 minutes Duration 15 minutes to 2 hours Unilateral, Side-locked-rarely switches sides Ipsilateral conjunctival injection and/or lacrimation Ipsilateral nasal congestion and/or rhinorrhea Ipsilateral miosis and/or ptosis 1-3 attacks per day. Awaken at night Described as excruciating, boring, burning pain; usually non-throbbing Kudrow L. Cluster headache: diagnosis and management. Headache (3): Cluster Headache Treatment Acute High flow O or 12-15L/m by NRBM Parental/Nasal DHE-Triptan Oral meds aren t fast enough Zolmitriptan 10 mg (off label) Preventive Steroid Burst (Decadron 12 mg day 1, 8 mg day 2, 4 mg day 3) Occipital Nerve Block with Steroids Verapamil must be instant release BID Increase to TID Titrate up until cluster stops or side effects intolerable EKG 3 days after dose increases >360mg & yearly Matharu M. Cluster headache. Clin Evid (Online) Feb 9 35 One Nerve Pathway: Multiple Symptoms of Migraine 36 12

13 Does Peter Have Sinus Headaches? 37 Diagnosis of Sinusitis Is Based on The Presence of At Least 2 Major or 1 Major + > 2 Minor Symptoms Major Symptoms Purulent nasal discharge Nasal congestion or obstruction Facial congestion or fullness Facial pain or pressure Loss of taste or smell Fever (acute sinusitis only) Minor Symptoms Headache Ear pain, pressure or fullness Halitosis Dental pain Cough Fever (for subacute or chronic sinusitis) Fatigue Chow AW et al. IDSA clinical practice guidelines for acute bacterial rhinosinusitis in children and adults. Clinical Infectious Disease. 2012: Patient_Care/PDF_Library/IDSA%20Clinical%20Practice%20Guideline%20for%20Acute%20Bacterial%20Rhinosinus itis% 20in% 20Children% 20and% 20Adults.pdf 38 Nasal Endoscopy No Headache With a moderate to severe sinus headache 1 hour after treatment with sumatriptan 6mg SC Reference: Schreiber CP et al. Arch Intern Med. 2004;164: Photos courtesy of Jeff Unger, MD 39 13

14 Strategies for Migraine Treatment Lifestyle Interventions Rescue Therapy When all else fails! Lipton RB, et al. Headache. 1998;38: Silberstein SD, et al. Cephalalgia. 1997;17: Behavioral Approach to Migraine No meal skips Exercise Sleep hygiene Avoid triggers Stop smoking Stop analgesics > 2 times weekly 2 cups java per day Relaxation exercises Have a written plan!! 41 Educate Patient Regarding The Diagnosis of Migraine Emphasize biologic and behavioral aspects of migraine. Reassure patient regarding migraine pathogenesis. Discuss treatment expectations: reduction in frequency, intensity, duration of headaches as well as limiting migraine disability. Engage patient in treatment plan. Answer questions

15 Acute Migraine Treatment Goals Headache free in 2 hours. Back to full function in 2 hours. Little to no side-effects from medication. Headache does not come back for 24 hours. Relief of associated symptoms. Acute medication not needed >2 times/week. 43 Triptans Sumatriptan Oral 25, 50, 100 mg Nasal 5, 20 mg Auto-injector 4 or 6 mg Needle-free injector 6 mg Sumatriptan nasal powder -11 mg Zolmitriptan Oral 2.5, 5 mg ODT 2.5, 5 mg Nasal 5 mg Naratriptan Oral 1, 2.5 mg ODT, orally disintegrating tablet Physicians' Desk Reference, th ed. Montvale, NJ: PDR Network, LLC; Rizatriptan Oral 5, 10 mg ODT 5, 10 mg Almotriptan Oral 6.25, 12.5 mg Frovatriptan Oral 2.5 mg Eletriptan Oral 20, 40 mg Sumatriptan/Naproxen Oral 85 mg/500 mg 44 Triptans Triptans are 5-HT 1B/D/F receptor agonists that attenuate migraine in many patients. Inhibit release of CGRP within the trigeminal vascular system. However, inhibition may be short lived. HAs can reoccur. 30 % of patients do not respond well to triptans, especially if drugs are used when the patient experiences peripheral and central sensitization. 45 Goadsby PJ, et al. Migraine-current understanding and treatment. New Engl J Med. 2002;346:

16 Triptan Dosing Strategies Treat early after migraine onset. Use highest dose formulation. Expect to be pain free and associated symptom free within 2 hours. If headache worsening after 2 hours, repeat dose x 1. If headache worsens typically after initial dosing, reduce dose of triptan by 50 % and add NSAID. Can dose ondansetron 4-8 mg for nausea. In presence of nausea consider SQ injection or nasal spray. If no response to triptan use rescue therapy. Keep a migraine diary to record frequency, intensity and duration of migraine. 46 Early Intervention: Triptan Efficacy vs. Pain Intensity 2 Hour Pain Free Response 80% 60% 40% 80% 58% 20% 35% 0% Mild Moderate Severe Pain Intensity When HA Treated Adopted from Cady RK et al SPECTRUM Study. Headache : When To Consider Preventive Therapy Migraine significantly interferes with patient s daily routine, despite acute treatment. Attack frequency >1/wk. Acute medication ineffective, contraindicated, over-used, or not tolerated. Patient preference. Presence of uncommon migraine conditions

17 Basic Rules For Migraine Prevention Pharmacology Remember, drugs used for migraine prevention were NOT developed initially to minimize migraine frequency. 70 % of patients may have intolerable side effects resulting in high rate of non-adherence after 6 months. Start low, advance slow (migraineurs are drug sensitive). Consider co-morbidities when prescribing preventative agents. Re-assess or increase dose of single agent after 6 weeks of use. Advise patient when they should expect to feel some improvement with preventative care. Consider tapering or discontinuing meds after 6 months. Goal is to reduce pain index by 50%. PTI= Intensity (0-10) x duration (hrs) + frequency/30 days. 7 x 8 hours over 10/30 days= Selecting Appropriate Preventive Therapy Take advantage of drug s side effects Underweight patient: pick a drug that produces weight gain Overweight: select drug that is not associated with weight gain Insomniac: use sedating tertiary TCAs at HS Elderly or cardiac patient: use divalproex or topiramate Athlete: avoid b-blockers 50 American Academy Neurology American Headache Society Preventive Recommendations Level A Divalproex Sodium Sodium valproate Topiramate Metoprolol Propranolol Timolol Frovatriptan* CGRP inhibitors Level B Amitriptyline Venlafaxine Atenolol Nadolol Naratriptan* Zolmitriptan* *= menstrual migraine 51 17

18 Herbal Preventives Butterbur (Petadolex) 75 mg twice a day 1 B2 (Riboflavin) 400 mg a day* Magnesium mg a day* Feverfew 3 dried leaves daily* Coenzyme Q mg a day Matchar DB, et al. AAN. US Headache Consortium. 2000:1-58. Level A evidence. Levin M. Headache 2012;52;S2: Markley H. Headache 2012;52:S2: *= Effective for pediatric migraine 52 Injection Pattern for OnabotulinumtoxinA-PREEMPT Technique ( Units) C C A A.Corrugator: 5 Units each side B. Procerus: 5 Units (one site) C. Frontalis: 10 Units each side D D C C B A D D 0.1 ml = (5 Units/site) D. Temporalis: 20 Units each side E E E E E. Occipitalis: 15 Units each side E E F F F G G G G G G F. Cervical paraspinals: 10 Units each side G. Trapezius: 15 Units each side F 53 Liberini et al. Neurol Sci May;35 Suppl 1:41-3 Menstrual Migraine Prevention Option Frovatriptan 2.5 mg BID x 6 days beginning 2 days prior to onset of period. Frovatriptan 10 mg at onset of period. Frovatriptan 2.5 mg qd x 6 days beginning 2 days prior to onset of period. Tepper, SJ. Treatment of menstrual migraine: evidence-based review. Manag Care Jul;16(7 Suppl 7):10-4; discussion Cady, RK, et al. Two center randomized pilot study of migraine prophylaxis comparing paradigms using pre-emptive frovatriptan or daily topiramate: research and clinical implications. Headache. 2012; 52 (5)

19 Why Patients Fail Not able to treat early Low and inconsistent oral absorption Unrecognized analgesic overuse Medical and psychiatric comorbidities 5HT receptor polymorphisms 55 Migraine Rescue Strategies Olanzapine 10 mg PO Quetiapine 100 mg PO Magnesium Sulfate 1 gram IV Push* Occipital nerve block* Sphenopalatine ganglion block* Use a sphenocath *= Office procedure by a family physician Krusz JC. Aggressive Interventional Treatment of Intractable Headaches In The Clinic Setting. In: Unger, J (ed). Clinics in Family Practice. Elsevier (Philadelphia) Sept Occipital Nerve Block Inject bupivacaine 0.5% 4 cc + triamcinolone 40 mg into the occipital notch on the side where patient perceives the majority of their head pain. Patient will note paresthesias lasting 6-12 hours on the side of the head where the injection was performed followed by significant headache relief lasting days to weeks. Unger Jeff, Cady Roger K, Farmer-Cady Kathleen. Understanding Migraine: Strategies for Prevention. Emergency Medicine. Oct

20 IV Magnesium-Aborting Migraine Within 15 Seconds! NO KIDDING 1 gram IV push over 1-2 minutes Side effect: severe hot flash lasting < 1 minute Eliminates migraine and migraine associated symptoms within 2-3 minutes Works best for HA < 24 hour duration. For HA > 24 hour duration use valproate (depakon) 500 mg IV push over 3-5 minutes 58 Chronic Migraine Decreased platelet 5-HT. Upregulation of 5-HT2A receptors, leads to increased NO synthesis. NO induces cerebral vasodilation and sensitized central and peripheral nocioceptors. Increased levels of Substance P and CGRP in CSF. Sensitization of central neurons potentiates pain response. 59 Becker WJ. The diagnosis and management of chronic migraine in primary care. Headache doi:10.111/head Episodic Migraine Frequent Episodic Migraine Headache Impact During Attack Incapacity Time to Recover Severity Frequency Normal Lipton RB, et al. Managing migraine: A healthcare professional s guide to collaborative migraine care. Hamilton, Ontario: Baxter Publishing Inc; 2008:

21 Chronic Migraine Chronic Migraine Incomplete Recovery Disease Impact Incapacity Comorbidies: Anxiety Depression Sleep disturbances Brain is highly Severity Frequency Headache reactive. Pt cannot recover. Migraines do Normal not stop. CGRP levels elevated 61 Lipton RB, et al. Managing migraine: A healthcare professional s guide to collaborative migraine care. Hamilton, Ontario: Baxter Publishing Inc; 2008:27. Catalysts of Transformation Overuse of acute treatment (> 2/ week) Analgesic use with each attack Head or neck trauma in a migraineur Genetics Obesity (> 30 kg/m2) Female gender/caucasian Earlier age of headache onset Oral contraceptive use Biondi D, In: Unger, J (ed). Clinics in Family Practice. Elsevier (Philadelphia) Sept Lipton, et al. Migraine: Epidemiology, Impact, and Risk Factors for Progression.45 (1) S3-S Caffeine Butalbital Opioids Ergots Triptans Acetaminophen NSAIDs OTC Tramadol Drugs Which Can Result In Analgesic Rebound Headache Decongestants 63 21

22 Free Iron Deposition in The PAG In a Patient With CDH Control Chronic Daily Headache Welch, et al. Periaqueductal Gray Matter Dysfunction in Migraine: Cause or the Burden of Illness? Headache (7) P With Permission CGRP (Calcitonin-gene related peptide) And Migraine CGRP is released from various locations in the body during times of physiologic or emotional stress CGRP sensitizes trigeminal afferents recruiting other nerves which can potentiate migraine As more nerves become sensitized, the thalamus becomes activated and patient develops central sensitization CGRP levels sampled from the external jugular vein are increased during migraine compared with controls who do not have migraine CGRP infusions can trigger migraine in migraineuers, but NOT healthy controls. CGRP inhibitors block migraine progression and reduce frequency, intensity and duration of migraine CRRP inhibition allows brain to recover more fully from a migraine event A brain which has not fully recovered from a migraine event is more reactive. Another migraine will follow Frequent migraine, result in more frequent events Juhasz G, et al. NO-induced migraine attack: strong increase in plasma calcitonin gene- related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Pain. 2003;106: CGRP And Migraine Migraine trigger Trigeminal Nerve activation Pain! 66 22

23 CGRP Inhibitor Prevents Migraine Migraine trigger Trigeminal Nerve activation 67 Treatment of Chronic Migraine Maximize behavioral interventions Stop MOH agents Address any comorbidities (MDD, GAD, sleep disturbances, obesity) Maximize acute treatment outcomes Consider nerve blocks CGRP inhibitors (not FDA approved) Referral for refractory patients Employ preventative medications: AEDs, mg, beta blockers, TCAs Botulinum toxin A CGRP Inhibitors 68 CGRP Inhibitors Pharmacologic target ALD403 (Not approved) CGRP w/humanized antibody Erenumab-Aimovig CGRP receptor with humanized antibody Galcanezumab- Emgality CGRP w/humanized antibody Fremanezumab Ajovy CGRP w/humanized antibody (CGRP ligand binding) Migraine target Episodic, chronic Episodic, chronic Episodic, chronic Episodic, chronic Dosing Single dose IV. 1 Gram. Efficacy lasts up to 6 months SC 70 and 140 mg monthly SC 240 mg loading dose 120 mg/month thereafter 225 mg/month 675 mg q 3 months (30 minute warmup time) Notes Drug inhibits action of CGRP and removes CGRP from receptors. Some patients have achieved complete remission Nearly 60 % reduction in episodic migraine vs PBO -50 % reduction in migraine frequency if > 15 HA days/month -75 % reduction if 4-14 HA days/mo 75 % reduction in headaches observed in 32 % of patients vs 16 % receiving PBO 1)Glamberadino MA, et al. Challenging chronic migraine: targeting the CGRP receptor. Lancet Neurol (6): )Ramon C, et al. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr Opion Neurol. 2017; 30 (3):

24 Cycle Breakers For Chronic Migraine Stop offending agent(s) Frovatriptan 2.5 mg at 4 pm daily x 8 days Dexamethasone PO x 3 days: 12 mg 8 mg 4 mg IV magnesium sulfate 1 gram stat, then 1 gram weekly x 3 doses total Occipital nerve block Sphenopalatine ganglion block Olanzapine 20 mg or quetiapine 100 mg x 7 days Dihydroergotamine 70 Summary Migraineurs are born with an inherently weak pain protective mechanism. Migraine headaches are recurrent and disabling. Migraine may be accurately diagnosed in patients who experience nausea, photophobia and/or disability during their headaches. Migraine interventions include lifestyle changes, preventative therapies, abortive drugs, and rescue therapies. Avoid prescribing opioids to migraineurs as they may induce neuroinflammation. Sinus headache? Treat for migraine Consider use of CGRP inhibitors for patients who have failed other preventative agents. 71 POST-TEST QUESTIONS 72 24

25 Post-test ARS Question 1 After participating in this program, how confident are you now in your ability to treat patients with chronic migraine? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 73 Post-test ARS Question 2 After participating in this program, how often will you now consider a diagnosis of migraine in a patient presenting with a chief complaint of headache? 1. Never 2. Rarely 3. Sometimes 4. Often 5. Always 74 Post-test ARS Question 3 Intravenous infusion of CGRP into an asymptomatic patient with migraine will result in which of the following events: 1. Hypotension 2. Syncope 3. Acute migraine 4. Cardiac arrhythmia 75 25

26 Thank You! Questions 76 26