Headache ppt

1. Origins of Pain in the Head Extra-cranial pain sensitive structures: Sinuses Eyes/orbits Ears Teeth TMJ Blood vessels 5,7,9,10 cranial nerves carry pain from thes strucure Intra-cranial pain sensitive structures: Arteries of circle of willis and proximal dural arteries, Dural Venous sinuses,veins Meninges Dura

2. Classification of Headaches PRIMARY - NO structural or metabolic abnormality: Tension Migraine Cluster SECONDARY – structural or metabolic abnormality: Extracranial: sinusitis, otitis media, glaucoma, TMJ ds Inracranial: SAH, vasculitis, dissection, central vein thrombosis, tumor, abscess, meningitis Metabolic disorders: CO2 retention, CO poisoing

3. RED Flags New onset headache in a patient >50 y.o. Sudden, worst headache of one’s life Morning headache associated with N/V Fever, weight loss Worsens with valsalva maneuvers Focal neurologic deficits, jaw claudication Altered LOC Hx of trauma, cancer or HIV

4. Primary Headache Types Migraine Tension Cluster Pain Description Throbbing, moderate to severe, worse w/exertion Pressure, tightness, waxes and wanes Abrupt onset, deep, continuous, excruciating, explosive Associated Symptoms Photo/phono-phobia, n/v, aura None Tearing, congestion, rhinorrhea, pallor, sweating Bajwa and Wootton. Up to Date 2007

5. Primary Headache Types Migraine Tension Cluster Location 60-70% unilateral Bilateral Unilateral Duration 4-72 hr Variable 0.5-3 hr, many per day Patient Appearance Resting in quiet dark room; young female Remains active or prefers to rest Remains active, prefers hot shower, male, smoker Bajwa and Wootton. Up to Date 2007

6. Pathophysiology Brainstem neuronal hyperexcitability Cortical spreading depression w/aura Abnormalities of 5-HT, CGRP, NE, DA, GABA, glutamate, NO, and endorphins Trigeminal Activation Marcus, DA. Headache Simplified 2008.

7. Presymptomatic hyperexcitabilty increases brain stem response to triggers Release of Neurotransmitters (5-HT, NE, DA, GABA, Glutamate, NO, CGRP, Substance P, Estrogen) Neurotransmitters activate the Trigeminal Nucleus Dilation of Meningeal blood vessels (Throbbing) Activation of Area Postrema (N/V) Activation of Hypothalamus (Hypersensitivity) Activation of cervical trigeminal system (Muscle spasm) Activation of Cortex and Thalamus (Head pain) Marcus, DA. Headache Simplified 2008.

8. 1.1 Migraine without aura Notes

9. 1.2 Migraine with aura

10. 1.2 Migraine with aura

11. 1.2 Migraine with aura Subtypes new to classification

12. 1.2.1 Typical aura with migraine headache

13. 1.2.1 Typical aura with migraine headache

14. 1.2.3 Typical aura without headache

15. Types of Migraine Treatment Acute Taken during an attack Reduces pain, associated symptoms and disability and stops progression Preventive Taken daily for months to years Reduces frequency, severity, and duration Used in addition to acute treatments .

16. Acute Treatment Principles Treat attacks rapidly and consistently Tailor treatment to the patient and the sx Minimize adverse events and cost Limit to 3 days per week or less

17. Antiemetics Prevent and treat nausea Improve GI motility Enhance absorption of other anti-migraine medications Limited RCT to support their use in migraine

18. Phenothiazines Promethazine ( Phenergan ) Available PO, IM, PR Dose = 25-50 mg Q6H PRN Blocks dopamine and histamine receptors Prochlorperazine ( Compazine ) Available PO, IM, IV, PR Dose = 5-10 mg Q6H PRN Blocks dopamine receptors SE = sedation, dizziness, dystonic rxn

19. Migraine Specific Medications Triptans Ergots

20. Acute Treatment - Triptans Fast onset/short duration Sumatriptan Rizatriptan Zomitriptan Almotriptan Eletriptan Treximet (Suma + Naproxen) Slow onset/long duration Naratriptan Frovatriptan

21. Acute Treatment - Triptans Reasonable first choice for patients with moderate to severe disability from migraines Limit use to 2-3 days per week Patients who fail one triptan often respond to another Do not use one triptan within 24 hours of another

22. Acute Treatment - Triptans Mechanism of action 5HT-1B/1D agonists Inhibit release of CGRP & substance P Inhibit activation of the trigeminal nerve Inhibit vasodilation in the meninges Precautions Ischemic heart dz or stroke High risk for CAD Pregnancy Hemiplegic or basilar migraine Ergots Use w/ SSRIs? Johnston et al Drugs 2010 Loder NEJM 2010

23. Triptan Side Effects Flushing, feeling or warmth Chest pressure or heaviness Throat tightness Paresthesias Dizziness, fatigue, drowsiness Nausea Intolerable taste with nasal formulations Johnston et al Drugs 2010 Loder NEJM 2010

24. Drug Tmax (h) T1/2 (h) Metabolism Sumatriptan 50 &100 mg tablets 2.5 2 MAO-A Sumatriptan 20 mg nasal 1 2 Sumatriptan 6 mg subQ 0.16-0.2 2 Zolmitriptan 2.5 mg tab 2 3 2D6 and MAO-A Zolmitriptan 2.5 mg ODT 3.3 2.5-3 Zolmitriptan 5 mg nasal 4 2.82 Rizatriptan 10 mg tab 1.2 2 MAO-A Rizatriptan 10 mg ODT 1.6-2.5 2 Naratriptan 2-3 5-6 P450, 50% unchanged Almotriptan 1.4-3.8 3.2-3.7 MAO-A, 3A4, and 2D6 Frovatriptan 2-4 26 Mostly unchanged Eletriptan 1-2 3.6-5.5 3A4 Triptan Comparison

25. Acute Treatment – Ergots Mechanism of Action Constrict peripheral and cranial blood vessels Bind to 5HT, NE, DA, alpha and beta receptors Contraindications and precautions CAD or CVD (or high risk), uncontrolled HTN Hemiplegic or basilar migraine Pregnancy (category X) and breast feeding Drugs metabolized by CYP3A4, triptans

26. Ergot Side Effects Nausea and vomiting (pre-treat with antiemetic) Coronary artery spasm, angina, MI Tingling, numbness, Dizziness Increased BP and HR “Ergotism”

27. Choosing Acute Rx Early N/V Nasal triptans Sumatriptan SubQ ODT triptans? Sensitive to SE Naratriptan Frovatriptan Almotriptan Recurrence Nara, Frova, Almotriptan Ergots Triptan + NSAID Rapid Onset Sumatriptan SubQ Nasal Triptans DHE nasal or IM

28. Indications for a Preventive Agent Migraine-related disability > 3d/month Migraines last over 48 hours Acute treatments are contraindicated, ineffective, or overused Migraines cause profound disability or prolonged aura Patient preference

29. Beta Blockers FDA approved for migraine prevention Propranolol (Inderal) 60-240 mg PO once daily for ER or divided BID or TID for IR Timolol (Blocadren) 10-30 mg PO daily in 2 divided doses Limited evidence for migraine prevention Nadolol (Corgard) 20-240 mg PO once daily Atenolol (Tenormin) 50-150 mg PO daily or divided BID Metoprolol (Lotensin, Toprol XL) 100-200 mg daily or divided BID for IR formulation

30. Beta Blockers Advantages Thoroughly studied and widely used Timolol (Blocadren) and propranolol (Inderal) are FDA approved Good choice for patients with HTN, CAD, tremor, or anxiety Disadvantages Side effects = fatigue, dizziness, depression, exercise intolerance, may worsen aura Avoid in patients with severe asthma, depression, bradycardia, Raynaud's, overt CHF

31. Calcium Channel Blockers . Although the mechanism by which calcium channel antagonists affect migraine is not known, . vasoconstriction , prevention of platelet aggregation and alterations in release and reuptake of serotonin. . Several trials have indicated some benefit for verapamil and flunarizine In recurrent migraine. . Verapamil in doses of 80 to 160   mg 3 times a day reduces the incidence of migraine with aura, but it is not as useful in migraine without aura.

32. Tricyclic Antidepressants Amitriptyline (Elavil) 10-200 mg nightly Nortriptyline (Pamelor) 10-150 mg nightly Desipramine (Norpramin) 25-200 mg nightly Imipramine (Tofranil) 10-200 mg nightly Doxepin (Sinequan) 10-200 mg nightly Lower end of dosage range is usually effective for migraine prevention

33. Tricyclic Antidepressants Advantages Inexpensive Once daily dosing Good choice for patients with insomnia, neuropathy, mood disorders, fibromyalgia Disadvantages None are FDA-approved Side effects = sedation, weight gain, dry mouth, urinary retention Avoid in sz disorder, cardiac conduction abnormalities, BPH

34. Other Antidepressants Efficacy not established in clinical trials Best for fluoxetine (Prozac) 20 mg daily Anectodal evidence for other SSRIs, trazodone, mirtazapine, bupropion, venalfaxine, and duloxetine Migraines are more likely to be poorly controlled if mood disorders are untreated

35. NSAIDs Long-acting agents taken on a scheduled basis have low risk of causing MOH Consider for patients who: Have other chronic pain conditions Frequently use short-acting NSAID for acute treatment Are at low risk for developing complications from daily NSAID Caution patients about exceeding maximum daily dose Limited evidence to support efficacy

36. NSAIDs Diclofenac 75 mg PO BID Naproxen 500 mg PO BID Meloxicam 7.5-15 mg PO daily Celecoxib 200 mg PO daily Aspirin 81-325 mg PO daily May be especially helpful for reducing aura

37. Antiepileptic Drugs (AEDs) FDA approved for migraine prevention Divalporex Sodium (Depakote) Topiramate (Topamax) Limited evidence for migraine prevention Gabapentin (Neurontin) Lamotrigine (Lamictal) Levetiracetam (Keppra) Zonisamide (Zonegran)

38. Divalproex Sodium (Depakote) Increases GABA and stabilizes nerve membrane activation thresholds Dose = 500 - 1500 mg daily divided BID or TID ER formulation allows for once daily dosing NNT = 2.8 to 4.2 (to ↓ migraine frequency 50%) Therapeutic plasma concentration = 50-100 mg/L

39. Divalproex Side Effects Common/dose related Tremor Drowsiness Nausea/vomiting Easy bruising Weight gain Nystagmus Rare/idiosyncratic Hepatotoxicity Pancreatitis Alopecia Thrombocytopenia Agranulocytosis Rash (SJS) Suicidal behavior

40. Topiramate (Topamax) - MOA Not completely understood Blocks NMDA receptors Blocks voltage dependant sodium channels Enhances GABA Weakly inhibits carbonic anhydrase .

41. Topiramate Dosing Dose titration in clinical trials: Initial dose = 25 mg daily Titrate by 25 mg every week No consistent additional benefit seen in doses >100 mg Dose titration in U of U Headache Clinic Initial dose = 12.5 mg at bedtime Titrate by 12.5 mg every week Goal of 50 mg BID May eventually increase up to 100 mg BID in certain patients

42. Topiramate Side Effects Common Paresthesias Cognitive problems Fatigue Weight loss Dizziness Nausea Taste perversion Rare or Serious Metabolic acidosis Depression Nephrolithiasis Glaucoma Oligohydrosis Suicidal behavior

43. Gabapentin (Neurontin) Mechanism of action Enhances GABA activity Binds to alpha-2-delta subunit of voltage gated calcium channels Inhibits high-voltage-activated calcium currents Result is decreased synaptic transmission Limited evidence from clinical trials for migraine prevention NNT = 3 (50% reduction in migraine frequency) Only 2 RCT, did not use typical migraine outcomes Vikelis and Rapoport. CNS Drugs 2010.

44. Botulinum Toxin Recently FDA approved for chronic migraine Dose = 155-195 units injected into muscles of face, neck and head Mecahnism of Action (purposed) Blocks release of Substance P and CGRP Inhibits peripheral signals to CNS and blocks central sensitization Dodick DW. Headache 2010.

45. Botulinum Toxin Efficacy Botulinum Toxin superior to placebo in 2 large, double blind, randomized, controlled trials Botulinum Toxin similar to topiramate and amitriptyline in small, shorter duration studies Botulinum toxin = placebo for episodic migraine Side effects = muscle weakness, injection site pain, and “spread of toxin effect”

46. Tension Type Headache Occurs in up to 80% of the population Most patients treat with OTCs and do not seek medical attention Pathophysiology unclear Theory of increased muscle tension is unproven Pain characteristics Bandlike , bilateral Extends form forehead to sides of temples Involves posterior neck muscles in cape-like distribution

47. Acute Treatment (Episodic TTH) First line: OTC analgesics (APAP, NSAIDs) Second line: ASA+APAP+caffeine, butalbital containing products High risk of rebound headaches Limit acute treatment to 2-3 days per week

48. Preventive Treatment (Chronic TTH) Non-Pharmacologic Proper sleep hygiene Stress management Acupuncture Biofeedback Physical therapy Pharmacologic TCAs (best efficacy) SSRIs (better tolerated) **Consider for patients with >15 headaches per month**

49. 3. Cluster headache and other trigeminal autonomic cephalalgias

50. Cluster Headache Abortive Treatment Inhalation of 100% oxygen up to 15 L/min Sumatriptan (Imitrex) 4-6mg subQ or 20 mg nasally Zolmitriptan (Zomig) 5-10 mg nasally or PO Dihdroergotamine (Migranal) 1 mg nasally up to 3 mg in 24 hours Prednisone 40-100 mg burst and taper Bajwa and Wootton. Up to Date 2007

51. Cluster Headache Prevention Verapamil 120-360 mg PO daily Lithium 300 mg PO BID to TID Divalproex 500-1500 mg PO daily to BID Topiramate 50-200 mg PO divided BID Prednisone 40-100 mg burst and taper Melatonin 3 mg PO QPM Bajwa and Wootton. Up to Date 2007

52. The Headache Diary Pain score Characteristics of the pain Associated symptoms Acute treatments used and response Triggers

53. The Headache Diary Makes the patient responsible for their disease Aids in diagnosis and differentiating between headache types Assesses efficacy of acute and preventive treatment Identifies triggers Minimizes recall bias

54. 4.5 Hypnic headache New entrant to classification

55. 4.8 New daily-persistent headache New entrant to classification

56. Disorder Demographic Clinical Features Recommended Treatments Chronic migraine Female/male, 3 : 1 Prevalence 2% Headache ≥15 days per month for >3 mo, of which ≥8 days meet ICHD-II criteria for migraine without aura or relief with triptan or ergot Topiramate , divalproex sodium, amitriptyline Chronic tension-type headache Equal sex ratio Prevalence 2% Mild-moderate severity; no migrainous symptoms; bilateral, nonthrobbing Amitriptyline New daily persistent headache Female > male Bilateral, persistent, moderately severe; may be preceded by viral infection; may resemble migraine or tension-type headache Amitriptyline Hemicrania continua Female > male Rare; unilateral, constant, exacerbations of severe headache, cranial autonomic symptoms, and ice-pick pain; responsive to indomethacin by definition Indomethacin Primary Chronic Daily Headache Disorders of Long-Duration (>4   h)

57. 9.1.1 Headache attributed to b acterial meningitis