Approach to a Patient with Headache

Transcription

1 Approach to a Patient with Headache J.D. Bartleson, MD Professor of Neurology Mayo Clinic College of Medicine 15 th Annual Internal Medicine Conference March 25, 2018 Boca Raton, FL 2014 MFMER slide-1

2 Disclosures I have no financial or other entanglements to disclose Many of the medications used to treat migraine are not specifically approved by the FDA for this indication 2014 MFMER slide-2

3 Objectives Determine when to obtain diagnostic tests in the patient with headache and know what tests to order Learn how to treat migraine headaches focusing on: Avoidance of headache triggers Treatment of the acute attack Preventive therapy, if appropriate 2014 MFMER slide-3

4 Diagnosing Headache The gold standard for headache diagnosis is: A careful history Neurological examination Pertinent physical examination Spend most of your time on the history! 2014 MFMER slide-4

5 International Classification of Headache Disorders, 3 rd Edition (ICHD-3)-Beta Four parts Primary headaches Secondary headaches Painful cranial neuropathies, other facial pains, and other headaches Appendix Full version pdf at content/uploads/2016/08/international-headache- Classification-III-ICHD-III-2013-Beta-1.pdf Full version (hyperlink) at Cephalalgia : MFMER slide-5

6 International Classification of Headache Disorders, 3 rd Edition The Primary Headaches Migraine Tension-type Cluster and other Trigeminal Autonomic Cephalalgias Other primary headaches Primary Stabbing HA, Cough HA, Exertional HA, HA with Sexual Activity, Hypnic HA, Thunderclap HA, Hypnic HA, and New Daily-persistent HA Secondary headaches which can mimic any primary HA Cephalalgia 2013;33: MFMER slide-6

7 ICHD, 3 rd Edition The Secondary Headaches Cephalalgia 2013;33: Trauma Vascular disorder Non-vascular intracranial Substance or substance withdrawal Disorder of homeostasis Skull and HEENT causes Psychiatric condition Other Infection 2014 MFMER slide-7

8 Headache Red Flags Abrupt onset split second or thunderclap headache Recent head or neck injury New onset or new type or worsening of existing headache New level of pain worst ever Triggered by Valsalva or cough Triggered by exertion Triggered by sexual activity Onset during pregnancy or puerperium Age > 50 years Neurologic signs or symptoms (seizures, confusion, findings) Systemic illness (fever, weight loss, scalp artery tenderness) Secondary risk factors (cancer, immunosuppressed, travel) De Luca + Bartleson Semin Neurol 2010;30: MFMER slide-8

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11 Headache Yellow Flags Not as Worrisome Headaches that wake patient from sleep at night Migraine, cluster, sleep apnea, rebound withdrawal, mass lesion, severe hypertension New onset side-locked headaches Trigeminal autonomic cephalalgias, head trauma, dissection, aneurysm, lung cancer Postural HA worse when upright suggests low CSF pressure (e.g., after LP or spontaneously) Postural HA worse if supine suggests brain tumor De Luca + Bartleson Semin Neurol 2010;30: MFMER slide-11

12 If You are Concerned About a Secondary Cause Diagnostic testing is warranted to exclude or confirm a secondary cause for the headache(s) Other factors that influence the decision: Need for diagnostic certainty, reassurance, meet patient and family expectations, medicolegal concerns, financial incentives, and faulty medical reasoning Brain imaging is the first, the best, and often the only diagnostic test needed Alternatively, could try treating as a primary HA disorder Bartleson Semin Neurol 2006;26: MFMER slide-12

13 MRI vs CT Brain Imaging CT better for acute onset symptoms and after trauma CT shows blood and fractures CT preferred for paranasal sinus disease MRI better for everything else shows pituitary, craniocervical junction, tumors, stroke, venous disease, MS, low and high CSF pressure, etc MR + CT angiography and venography are = for atherosclerosis, aneurysm, dissection, vasculitis MRI does not use X-rays and dye is safer MRI shows too much! 2014 MFMER slide-13

14 MRI Shows Too Much Rotterdam Population Study of 2,000 Persons Asymptomatic brain infarcts in 7.2% Cerebral aneurysms in 1.8% Benign primary brain tumors in 1.6% Arachnoid cysts 1% Type I Chiari malformation 1% Also shows incidental sinus disease Vernooij et al N Engl J Med 2007;357: MFMER slide-14

15 Other Headache Diagnostic Tests Myelogram, isotope cisternogram for low CSF pressure Dental and TMJ radiographs for face and jaw pain Blood tests for systemic illnesses (e.g., temporal arteritis) Polysomnography for sleep apnea CSF for meningitis, low and high CSF pressure Plasma + urine catecholamines for pheochromocytoma CO level for carbon monoxide poisoning Blood tests for thyroid function, insulinoma Chest imaging for ipsilateral pain due to apical lung tumor 2014 MFMER slide-15

16 Migraine is Extremely Common Up to 20% of Women, 10% of Men Any episodic headache should be considered migraine with the likelihood increasing if: Pain is asymmetric or unilateral Pain has a throbbing quality Pain is severe Pain is accompanied by nausea and/or sensitivity to light, noise, and/or smells Typical migraine aura symptoms Positive family history of migraine (found in 2/3 rds ) 2014 MFMER slide-16

17 Treatment Strategies for Migraine (and Other Headaches) Identify and avoid headache triggers Acute therapy of the individual attack Preventive therapy, if needed Bartleson + Cutrer Minnesota Medicine 2010;93: MFMER slide-17

18 Migraine Triggers Going too long without eating Alcohol Hormonal contraceptives Hormone replacement therapy Caffeine and caffeine withdrawal Stress or release from stress Too little or too much sleep 2014 MFMER slide-18

19 Migraine Triggers Continued Menstruation Fatigue Exposure to bright or flickering lights, loud noises, smoke, and strong scents Change in the weather Acute head trauma 2014 MFMER slide-19

20 Migraine Food Triggers Usually Within 12 to 24 Hours Chocolate Aged cheeses Processed meats Fermented foods Aspartame Monosodium glutamate Citrus fruits Nuts Supplements 2014 MFMER slide-20

21 The Trouble with Triggers Most migraine attacks are not triggered Many triggers are unavoidable Response to a trigger is variable Impairs trigger recognition Reduces the patient s willpower to regularly avoid a recognized trigger 2014 MFMER slide-21

22 Treatment Strategies for Migraine (and Other Headaches) Identify and avoid headache triggers Acute therapy of the individual attack Preventive therapy, if needed Bartleson + Cutrer Minnesota Medicine 2010;93: MFMER slide-22

23 Goals of Acute Migraine Treatment Treat attacks rapidly, effectively, and consistently Restore the patient s sustained ability to function Minimize need for rescue treatments, ER visits Optimize self-care and reduce resource utilization Be cost-effective Have minimal or no adverse side effects Avoid medication overuse and rebound withdrawal 2014 MFMER slide-23

24 Acute Therapy of Migraine Early treatment is critical Rest early in the course can be very helpful Many medication options are available The mainstay of therapy for most patients Early treatment is critical many patients wait too long and miss a window of opportunity 2014 MFMER slide-24

25 Acute Migraine Treatment Options Nonspecific NSAIDs Acetaminophen Combination drugs Specific antimigraine Triptans Dihydroergotamine and ergotamine Antinauseants and neuroleptics Opioid analgesics 2014 MFMER slide-25

26 Acute Migraine Therapy Single ingredient oral OTC and prescription analgesics Acetaminophen 650-1,000 mg max 3 gm/day Aspirin 650-1,000 mg Naproxen sodium mg max 1100 mg/day Ibuprofen mg max 3200 mg/day Ketoprofen mg max 300 mg/day Diclofenac potassium oral solution mg max 200 mg/day 2014 MFMER slide-26

27 Acute Migraine Therapy Combination OTC analgesics Excedrin Migraine = Excedrin Extra Strength = 250 mg acetaminophen, 250 mg aspirin, and 65 mg caffeine Anacin = aspirin and caffeine Tylenol PM = Excedrin PM = acetaminophen and diphenhydramine Aleve PM and Advil PM also contain diphenhydramine 2014 MFMER slide-27

28 Acute Migraine Therapy Multi-ingredient prescription medications Midrin = isometheptene, dichloralphenazone, APAP Acetaminophen (APAP) with codeine Vicodin, Lorcet, Lortab, Norco = hydrocodone/apap Percocet, Roxicet, Tylox, Endocet = oxycodone/apap Fiorinal, Fioricet, Esgic, Phrenilin = butalbital with ASA or APAP with/without caffeine and some with codeine Ergotamine ± caffeine tablets and suppositories APAP = acetaminophen 2014 MFMER slide-28

29 Acute Migraine Therapy Ketorolac (Toradol) mg IM Tramadol (Ultram) mg PO Stronger opioid analgesics, parenterally or PO, often with an adjuvant Adjuvants include: Hydroxyzine (Vistaril) mg IM or PO Metoclopramide (Reglan) 10 mg IV or PO Prochlorperazine (Compazine) 5-10 mg IV, IM or PO; mg PR Promethazine (Phenergan) mg IV, IM, PO or PR Caffeine 65 mg PO 2014 MFMER slide-29

30 Acute Migraine Therapy Antinauseants Prochlorperazine (Compazine) 5-10 mg IM/IV/PO or mg PR Promethazine (Phenergan) mg IM/IV/PO/PR Metoclopramide (Reglan) 10 mg IV/PO (also prokinetic) Droperidol mg IM/IV Ondansetron (Zofran) 4-8 mg PO 2014 MFMER slide-30

31 5-Hydroxytryptamine Agonist Therapy The Triptans Almotriptan = Axert Eletriptan = Relpax Frovatriptan = Frova Naratriptan = Amerge Rizatriptan = Maxalt Sumatriptan = Imitrex Zolmitriptan = Zomig 2014 MFMER slide-31

32 Acute Rx with 5 HT 1B/1D Agonists Sumatriptan (Imitrex) is available as: 6 mg SQ autoinjector, MR once after 1 hour Intranasal spray 20 mg or 5 mg to one nostril or 5 mg to each nostril, MR once after 2 hours 25 mg, 50 mg or 100 mg tablets PO, MR q 2 hours, not > 200 mg in 24 hours Treximet (a tablet with 85 mg of sumatriptan and 500 mg of naproxen), MR once after 2 hours Needle-free injectable (Sumavel ) Breath actuated intranasal powder (Onzetra ) MR = May Repeat Underlined is the usual optimum dose 2014 MFMER slide-32

33 Acute Rx with 5 HT 1B/1D Agonists Rizatriptan (Maxalt) 5 or 10 mg regular or oral dissolving tablets PO, MR x 2 at intervals of 2 hours not to exceed 30 mg in 24 hours. Use 5 mg dose if patient is on propranolol. Pretty quick and effective. Eletriptan (Relpax) 20 mg vs 40 mg PO, MR q 2 hours not to exceed 80 mg in 24 hours. Fairly quick and effective. Avoid in patients on potent CYP3A4 enzyme inhibitors. Underlined is the usual optimum dose 2014 MFMER slide-33

34 Acute Rx with 5 HT 1B/1D Agonists Zolmitriptan (Zomig) 2.5 or 5 mg regular or oral dissolving tablets PO, MR once after 2 hours not to exceed 10 mg in 24 hours. Use lower dose if on cimetidine. Zomig Nasal Spray 2.5 or 5 mg intranasally, MR once after 2 hours not to exceed 10 mg in 24 hours. Almotriptan (Axert) 6.25 or 12.5 mg PO, MR q 2 hours, not to exceed 25 mg in 24 hours. Pretty quick, fairly long duration, fewer side effects. Underlined is the usual optimum dose 2014 MFMER slide-34

35 Acute Rx with 5 HT 1B/1D Agonists Frovatriptan (Frova) 2.5 mg PO, MR q 2 hours, not to exceed 7.5 mg in 24 hours. Longer duration of action. Naratriptan (Amerge) 1 mg or 2.5 mg PO, MR once after 4 hours not to exceed 5 mg in 24 hours. Longer duration of action. Contraindicated with severe hepatic or renal impairment. Underlined is the usual optimum dose 2014 MFMER slide-35

36 Acute Rx with Dihydroergotamine (DHE) a Non-triptan 5 HT 1B/1D Agonist Dihydroergotamine (Migranal) nasal spray 0.5 mg to each nostril, repeated once after 15 minutes. Avoid in severe hypertension, pregnancy, if nursing, on potent CYP3A4 inhibitors. DHE also available for SQ, IM, or IV injection mg q 1 hour, not > 3 mg in 24 hours. Ergotamine tartrate (Wigraine, Cafergot) available 1 or 2mg PO or PR is little used. Underlined is the usual optimum dose 2014 MFMER slide-36

37 Acute Migraine Therapy Recent meta-analysis found eletriptan (Relpax) most effective at 2 and 24 hours followed by rizatriptan (Maxalt) then zolmitriptan (Zomig) Sumatriptan (Imitrex) and DHE injections work faster than sumatriptan (Imitrex), zolmitriptan (Zomig), and DHE (Migranal) nasal sprays which act faster than tablets Rizatriptan (Maxalt) enters the blood stream more rapidly than other oral triptans Naratriptan (Amerge), frovatriptan (Frova), and DHE (Migranal nasal spray or by injection) have longest half-lives Dissolving tablets don t reach bloodstream faster! Thorlund et al Cephalalgia 2014;34: MFMER slide-37

38 Acute Migraine Therapy Use shot, nasal spray, or oral dissolving tablet or add an antinauseant if patient has early vomiting If a patient does not respond to one triptan, they may respond to another Make sure they use an adequate dose soon enough If headache returns, should repeat dose as allowed Try at least 2 triptans for 2-3 attacks each If oral triptan doesn t work, try SQ sumatriptan Triptans help 4 out of 5 patients Does response to a triptan confirm diagnosis of migraine? No, but I sleep better 2014 MFMER slide-38

39 New Therapies Cefaly : Electrical stimulation of medial brow can be used acutely or daily as a preventive stms : Transcranial Magnetic Stimulation acutely for migraine with or without aura or daily for migraine prevention GammaCore : External vagal nerve stimulation acutely Sphenopalatine ganglion blocks with local anesthetic May include insertion of a delivery device Can be used acutely or preventively 2014 MFMER slide-39

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42 Acute Treatment Strategies Step or staged care Start with a weaker medication If needed, increase strength of drug Stratified care Use best medication for this headache based on The current headache (e.g., type, severity) Patient s experience with different treatments Hit me with your best shot Use the medication most likely to help every time 2014 MFMER slide-42

43 Rational Polypharmacy of the Acute Attack NSAID or APAP plus an antinauseant Triptan plus NSAID (see Treximet) or APAP Triptan plus an antinauseant Triptan plus NSAID or APAP plus an antinauseant APAP = acetaminophen 2014 MFMER slide-43

44 The Trouble With Triptans Triptans cause chest and neck pressure, tingling, nausea Estimated risk of a serious CV event is 1 in 4 million uses Avoid triptans in patients with or at high risk for CAD DHE has a lower risk of chest discomfort but a high incidence of GI side effects If there is concern about underlying coronary artery disease and a great need to treat the headaches: Evaluate and treat the heart disease, then try triptan Give triptan under medical surveillance Risk of serotonin syndrome if triptans used with SSRIs or SNRIs is almost nil But I inform patients about possible symptoms Loder New Engl J Med 2010;363: MFMER slide-44

45 Contra-indications to 5 HT 1B/1D Agonists Known or suspected: Ischemic heart disease (atherosclerotic or vasospastic) Peripheral vascular disease Cerebrovascular disease WPW syndrome Uncontrolled hypertension Other 5 HT 1B/1D agonists within preceding 24 hours Hemiplegic or basilar migraine (latter is now called migraine with brainstem aura) MAO inhibitor therapy in preceding 2 weeks For DHE and ergotamine, above plus pregnancy and lactation 2014 MFMER slide-45

46 Treatment Strategies for Migraine (and Other Headaches) Identify and avoid headache triggers Acute therapy of the individual attack Preventive therapy, if needed Bartleson + Cutrer Minnesota Medicine 2010;93: MFMER slide-46

47 When to Consider Preventive Antimigraine Treatment More than 4 to 6 headache days per month When acute therapy is contraindicated or ineffective When acute treatment is needed more than twice a week For severe migraine attacks (e.g., hemiplegic migraine) For even infrequent attacks that affect safety (e.g., pilot) or livelihood (e.g., professional athlete) Patient preference 2014 MFMER slide-47

48 Goals of Preventive Therapy Decrease attack Frequency Severity Duration Improve response of attacks to acute therapy Improve function, decrease disability Prevent medication overuse and chronic migraine headaches 2014 MFMER slide-48

49 Preventive Antimigraine Rx Dose response relationship is variable Start low and slowly increase dose To reduce side effects To avoid overshooting a beneficial response Medications take 3-4 weeks to 3-4 months to work Full benefit may take 6 months 50% decrease in headache burden is a good result If helpful, continue for 6-12 months then reassess Preventive therapy is underutilized 2014 MFMER slide-49

50 Preventive Antimigraine Therapies from American Academy of Neurology (AAN) Silberstein et al Neurology 2012;78: Level A Evidence Antiepileptic drugs Divalproex Topiramate Beta blockers Metoprolol Propranolol Timolol Level B Evidence Antidepressants Amitriptyline Venlafaxine Beta blockers Atenolol Nadolol 2014 MFMER slide-50

51 Preventive Antimigraine Therapies Level A from Recent AAN Evidence-based Guideline Divalproex start at aim for mg/day Alopecia, weight gain, tremor, birth defects Topiramate start at aim for mg/day Mental slowing, kidney stones, weight loss, birth defects Metoprolol start at aim for mg/day Depression, fatigue, hypotension, bradycardia Propranolol start at aim for mg Same side effects as metoprolol Timolol start at mg aim for mg/day Same side effects as metoprolol Silberstein et al Neurology 2012;78: MFMER slide-51

52 Preventive Antimigraine Therapies Level B from Recent AAN Evidence-based Guideline Amitriptyline start at aim for mg/day Weight gain, dry mouth, sedation, constipation Venlafaxine start at aim for mg/day Nausea, sleep disturbance, asthenia, nervousness Atenolol start at aim for mg/day Depression, fatigue, hypotension, bradycardia Nadolol start at aim for mg/day Same side effects as atenolol Silberstein et al Neurology 2012;78: MFMER slide-52

53 Preventive Antimigraine Therapies with Less Evidence from AAN Guideline Holland et al Neurology 2012;78: Prescription drugs Verapamil Gabapentin Some Rx NSAIDs On a daily basis Lisinopril Candesartan Non-prescription drugs Some OTC NSAIDs On a daily basis Magnesium Riboflavin (vitamin B2) Co-Q10 Petasites (butterbur root, Petadolex ) with Level A evidence but recent reports of liver damage 2014 MFMER slide-53

54 Preventive Antimigraine Therapies That are Used with Less Evidence Verapamil start at aim for mg/day Hypotension, constipation, swelling Gabapentin start at aim for mg/day Edema, sedation, fatigue, weight gain, dizziness Regular use of NSAID (ibuprofen, ketoprofen, naproxen) GI upset, hypertension, kidney damage Magnesium 300 mg/day: Diarrhea and other GI effects Riboflavin (vitamin B2) 400 mg/day: Itching, dark urine Co-Q mg three times/day: Mostly GI side effects I would not recommend use of Petasites (butterbur root) due to reports of hepatoxicity Holland et al Neurology 2012;78: MFMER slide-54

55 How to Choose a Preventive Antimigraine Treatment Pick a medication that will treat another condition Beta blocker in a patient with hypertension Avoid a drug that could aggravate an existing condition Divalproex in someone who is overweight Consider the cost, risk/safety, side effects, ease of use But don t avoid a preventive with good evidence Be aware of potential drug interactions (e.g., topiramate and BCPs) Avoid drugs that could cause birth defects in women Neural tube defects with divalproex Cleft lip/palate with topiramate Obtain input from patient they have the final say Margulis et al Am J Obstet Gynecol 2012;207:405.e MFMER slide-55

56 Why Preventives Don t Work in Migraine Starting dose was too high and side effects occurred Dose advanced too quickly and side effects occurred Dose was not pushed high enough Trial was too short Preventive helped but patient not satisfied or didn t notice Patient was in rebound due to medication overuse when preventive therapy is less likely to be beneficial Occasionally using 2 preventives together is helpful Tricyclic agent with a beta blocker or verapamil Without good evidence for synergism 2014 MFMER slide-56

57 New Preventive Antimigraine Therapy Recent reports of benefit from injections of monoclonal antibodies directed at calcitonin generelated peptide receptors (CGRP) or CGRP itself Found to be helpful for chronic migraine and preventing episodic migraine headaches New mechanism of action High hopes for benefit from this class of drugs Hershey N Engl J Med 2017;377: Silberstein et al N Engl J Med 2017;377: Goadsby et al N Engl J Med 2017;377: MFMER slide-57

58 Chronic Migraine Can be Treated with Onabotulinum A Injections into Scalp Muscles Chronic migraine (CM) is defined as: Headache on 15 days per month for > 3 months The headaches have features of migraine on 8 days per month for > 3 months CM can be caused or simulated by overuse of acute drugs (analgesic or triptan) or substances (caffeine) So-called medication overuse headache Can have both CM and medication overuse CM patients usually referred to headache specialist The International Classification of Headache Disorders, 3 rd Ed 2014 MFMER slide-58

59 Onabotulinumtoxin A Injections FDA Approved in 2010 for Chronic Migraine, not Frequent Migraine

60 Approach to a Patient with Headache I Look Forward to Your Questions J.D. Bartleson, MD Professor of Neurology Mayo Clinic College of Medicine Bartleson.john@mayo.edu 2014 MFMER slide-60