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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, ce
ntral 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
8. 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.
9. 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
Cortex and
Thalamus (Head
pain)
Marcus, DA. Headache Simplified 2008.
Activation of
cervical trigeminal
system (Muscle
spasm)
24. 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
.
25. 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
26. Antiemetics
• Prevent and treat nausea
• Improve GI motility
• Enhance absorption of other anti-migraine
medications
• Limited RCT to support their use in migraine
27. 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
30. 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
31. 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
Johnston et al Drugs 2010
Loder NEJM 2010
Precautions
• Ischemic heart dz or
stroke
• High risk for CAD
• Pregnancy
• Hemiplegic or basilar
migraine
• Ergots
• Use w/ SSRIs?
32. 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
34. 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
35. Ergot Side Effects
• Nausea and vomiting (pre-treat with antiemetic)
• Coronary artery spasm, angina, MI
• Tingling, numbness, Dizziness
• Increased BP and HR
• “Ergotism”
36. Choosing Acute Rx
Early N/V
Recurrence
• Nasal triptans
• Sumatriptan SubQ
• ODT triptans?
• Nara, Frova, Almotriptan
• Ergots
• Triptan + NSAID
Sensitive to SE
Rapid Onset
• Naratriptan
• Frovatriptan
• Almotriptan
• Sumatriptan SubQ
• Nasal Triptans
• DHE nasal or IM
37. 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
38. 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
39. 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, bradycar
dia, Raynaud's, overt CHF
40. 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.
41. 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
42. Tricyclic Antidepressants
Advantages
• Inexpensive
• Once daily dosing
• Good choice for patients
with
insomnia, neuropathy, m
ood
disorders, fibromyalgia
Disadvantages
• None are FDA-approved
• Side effects = sedation,
weight gain, dry mouth,
urinary retention
• Avoid in sz disorder,
cardiac conduction
abnormalities, BPH
43. 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
44. 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
45. 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
50. 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
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–
–
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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
51. 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
52. Gabapentin (Neurontin)
• Mechanism of action
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–
–
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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.
53. 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.
54. 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”
56. 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
57. 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
61. 3.1 Cluster headache
3.1.1 Episodic cluster headache
A. Attacks fulfilling criteria A-E for 3.1 Cluster
headache
B. At least two cluster periods lasting 7-365 d and
separated by pain-free remission periods of 1 mo
3.1.2 Chronic cluster headache
A. Attacks fulfilling criteria A-E for 3.1 Cluster
headache
B. Attacks recur over >1 y without remission periods
or with remission periods lasting <1 mo
62. 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
63. 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
64. The Headache Diary
• Pain score
• Characteristics of the pain
• Associated symptoms
• Acute treatments used and response
• Triggers
65. 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
72. Primary Chronic Daily Headache Disorders of Long-Duration (>4 h)
Disorder
Demographic
Clinical Features
Recommended Treatments
Chronic migraine
Headache ≥15 days per month
for >3 mo, of which ≥8 days
Female/male, 3 : 1 Prevalence
Topiramate, divalproex sodium,
meet ICHD-II criteria for
2%
amitriptyline
migraine without aura or relief
with triptan or ergot
Mild-moderate severity; no
Chronic tension-type headache Equal sex ratio Prevalence 2% migrainous symptoms; bilateral, Amitriptyline
nonthrobbing
New daily persistent headache Female > male
Bilateral, persistent, moderately
severe; may be preceded by
viral infection; may resemble
Amitriptyline
migraine or tension-type
headache
Hemicrania continua
Rare; unilateral, constant,
exacerbations of severe
headache, cranial autonomic
Indomethacin
symptoms, and ice-pick pain;
responsive to indomethacin by
definition
Female > male
NOT in Handout!!Similar choice for pt with rapid onset of migraine and with early n/v – need something non-oral or that works fastRecurrence = migraine initially gone, but comes back within 24 hours, something longer acting may outlast the migraine and keep it from coming back or addition of NSAID that lasts longer than triptanNara, Frova and Almo have lower rates of SE vs. other triptans and may be tolerated when other triptans were notNasal formulation available for sumatriptan, zolmitriptan, and DHEODT formulations available for rizatriptan and zolmitriptan
NNT not in handout
SJS = Steven’s Johnson SyndromeSuicidal behavior and AEDs – FDA pooled data of all RDBPCT trials of AEDs showed 0.43% of pt on AEDs vs. 0.24% of pt on placebo reported suicidal behavior, regardless of indication. Translates to 1 additional case of suicidal behavior/ideation per 530 pt. treated with AED. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100192.htm