25 - Migraine/Headache Flashcards
1
Q
Pathophysiology of migraine
A
- Complex phenomenon – vascular theory (vasodilation of cerebral vasculature = headache; vasoconstriction = aura) is no longer appropriate on its own
- Is a neurological disorder
- Cortical spreading depression phenomenon (CSD) thought to -> cause migraine aura, activate trigeminal nerve afferents, and disrupt blood-brain barrier permeability
- Sensitization (peripheral and central) -> nerves become more responsive to stimuli
- Know that activation of serotonin receptors is key for acute migraine tx, but we don’t really know why (many theories)
2
Q
Migraine subtypes
A
- Acute or “episodic” migraine w/ or w/o aura
- Chronic migraine w/ or w/o aura
3
Q
Diagnostic criteria – acute migraine w/o aura **know this
A
- At least 5 attacks fulfilling criteria 2 through 4
- Headache attacks lasting 4 to 72 h (untreated or unsuccessfully treated)
- Headache has at least 2 of the following characteristics -> unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity
- During headache at least 1 of the following -> N, V, or both; photophobia and phonophobia
4
Q
Diagnostic criteria – acute migraine w/ aura **know this
A
- At least 2 attacks fulfilling criterion 2 and 3
- One or more of the following fully reversible aura sx:
- Visual -> flickering lights, flashes, lines/shapes, spots
- Sensory -> tingling and/or numbness of 1 limb, side of face and/or mouth/tongue
- Speech and/or language -> aphasia/dysphasia, word-finding
- Motor -> muscle weakness, loss of function
- Brainstem -> dizziness, loss of balance
- Retinal -> partial visual loss - At least 2 of the following 4 characteristics:
- At least 1 aura sx spreads gradually over 5 or more minute, and/or 2 or more sx occur in succession
- Each individual aura sx lasts 5-60 mins
- At least 1 aura sx is unilateral
- Aura is accompanied, or followed w/in 60 mins, by headache
5
Q
Diagnostic criteria – chronic migraine w/ or w/o aura **know this
A
- Headache (tension-type-like and/or migraine-like) on 15 or more days/month for > 3 months and fulfilling criteria 2 and 3
- Occurring in a pt who has had at least 5 attacks fulfilling criteria 2-4 for “acute migraine w/o aura” and/or criteria 2 and 3 for “acute migraine w/ aura”
- On 8 or more days/month for > 3 months, fulfilling any of the following:
- Criteria 3 and 4 for “acute migraine w/o aura”
- Criteria 2 and 3 for “acute migraine w/ aura”
- Believed by the pt to be migraine at onset and relieved by a triptan or ergot derivative
6
Q
Migraine phases
A
- Phase 1 = prodrome
- Phase 2 = aura
- Phase 3 = early headache
- Phase 4 = late headache
- Phase 5 = postdrome
7
Q
Premonitory sx (prodrome)
A
- ~24-48 h before onset of headache
- Neurologic sx (ex: allodynia, phonophobia, photophobia, hypersomnia, and difficulty concentrating)
- Psychological (ex: anxiety, depression, euphoria, drowsiness, fatigue)
- Autonomic (ex: polyuria, diarrhea, constipation)
- Constitutional (ex: stiff neck, yawning, thirst, food cravings)
8
Q
Describe phase 2 (aura)
A
- Can precede and/or be present during headache
- Lasts < 60 mins
- Completely reversible
- Mix of positive and negative focal neurological sx (not just visual and sensory):
- Visual -> positive = flickering lights, spots, lines; negative = loss of vision
- Sensory -> positive = pins and needles; negative = numbness
9
Q
Characteristics of a typical migraine headache **know this
A
- Unilateral (most often), but not always on the same side
- Throbbing, pulsating
- Attack progressively worsens over hours
- Often N and V (vomiting less common)
- Photophobia/ phonophobia (very common) -> often migraine sufferer will need to rest in dark, quiet room b/c of this
- Osmophobia and cutaneous allodynia
10
Q
Red flag migraine sx
A
- Age of onset > 50 y/o
- Severe and abrupt onset
- Sx worsening over days/weeks
- Neurologic signs -> stiff neck, focal signs, reduced consciousness, abnormal speech, cognitive impairment
- Systemic signs -> fever, rash, N/V
- New onset cancer, lyme disease, HIV
- Triggered by cough, exertion, sexual activity
11
Q
Migraine and stroke risk
A
**Take home message = women who have migraine w/o aura and no other risk factors for stroke may use a contraceptive pill w/ < 50 mcg estrogen; women who have migraine w/ aura should be encouraged to stop smoking, control their BP, and use an alternative method of contraception
12
Q
Potential migraine triggers
A
- Most common = emotional stress, hormones in women, not eating, weather, sleep disturbances
- Moderately common = odours, neck pain, lights, alcohol, smoke, sleeping late, heat, food
- Less common = exercise, sexual activity
13
Q
Non-pharms for migraine
A
- *Avoid triggers, hydration, maintain routine
- Rest/sleep in dark, quiet room
- Headache diary
- Stress management
- Cold/heat packs
- Regular meals, caffeine balance
14
Q
Pharmacotherapy options for migraine
A
- Acute drug treatment (abortive medications, “relievers”) -> taken prn for headache sx
- Preventative drug tx -> aim to decrease migraine frequency; taken on a regular basis
15
Q
Goals of acute therapy
A
- Relieve pain and associated sx of migraines
- Functional headache-free state in 2 h w/ no recurrence in 24 h
- Minimal or no adverse effects
- Relieve migraine-related disability so that pt can return quickly to normal function
- Avoid medication overuse headache and development of central sensitization (when abortive medications are less effective; can be prevented w/ early tx)
16
Q
Benefit to treating the headache early
A
- Early tx reduces overall burden of migraine (and reduces likelihood of central sensitization)
- Challenges:
- Some avoid medication unless headache is severe b/c of cost and SE
- Some w/ frequent attacks limit acute medication for fear of overuse
17
Q
Migraine – acute pharmacotherapy options
A
- Triptans (5-HT receptor agonists) *migraine specific
- Ergot derivatives (nonselective 5-HT agonist) *migraine specific
- NSAIDs, acetaminophen
- Domperidone, metoclopramide, prochlorperazine (anti-emetic)
- *Best if taken early in attack (ie: at onset of head pain); taking at aura may be too soon
18
Q
Triptans for migraine (role, efficacy, MOA, CI)
A
- Role -> moderate to severe migraine attacks (1st line)
- Don’t seem as effective if taken during aura (take at pain onset)
- All effective in reducing N/V, photo and phonophobia
- 1/3 of px may not respond to triptan -> may benefit from switching to a different triptan (space 24 h)
- MOA in migraine unclear (vasoconstrictor but also inhibits neurogenic inflammation peripherally and prevents central sensitization)
- CI in px w/ CAD (despite evidence to suggest safe use)
- Can use SC, ODT, or intranasal formulations if headache builds rapidly or is accompanied by early N/V; more expensive
- All triptans require dose adjustment in liver dysfunction (some CI); some require dose adjustment in renal dysfunction
19
Q
Drug-drug interactions w/ triptans
A
- Don’t take w/in 24 h of ergot alkaloid (additive vasoconstriction)
- Avoid w/in 2 weeks of MAOIs
- Caution w/ SSRI/SNRI (serotonin syndrome rare)
- CYP3A4 inhibitors
- Propranolol can increase serum concentrations of certain triptans (mostly rizatriptan, so reduce dose if needed)
20
Q
Triptans SE
A
- Common = paresthesia’s, fatigue, dizziness, flushing, warm sensations, somnolence
- “Triptan sensations” = mild and transient burning, tingling, tightness, pressure, pain in face/chest/neck/throat
- Serious but rare = MI, coronary vasospasm w/ ischemia, serotonin syndrome
- CI = cerebrovascular disease, IHD (angina, post-MI), uncontrolled HTN, PVD, hemiplegic or basilar migraine
21
Q
Ergots for migraine (role, MOA)
A
- 1st line for severe/ultra-severe attacks
- Non-selective 5-HT agonist
- Also, alpha + beta-adrenergic agonist and dopamine D1 + D2 agonist (contributes to SE rather than migraine relief)
- Brand name = migranal (dihydroergotamine)
- Slower onset of action and less migraine recurrence than sumatriptan SC/IN
- More N/V (pre-dose w/ antiemetic) but less chest pain than triptans
22
Q
Ergots SE
A
- Common = N/V, abdominal pain, weakness, fatigue, muscle pain, diarrhea
- Serious = severe peripheral ischemia (cold, numb, painful extremities), gangreneous extremities, MI, hepatic necrosis, bowel and brain ischemia
- CI = cardiac/ cerebrovascular disease, uncontrolled HTN, pregnancy, hemiplegic or basilar migraine
- Don’t use w/in 12 h of triptans
23
Q
Acetaminophen for migraine (role, efficacy)
A
- Role -> acute migraine tx of mild to moderate severity; pt w/ CI or intolerance to NSAIDs
- Best if taken early
- May be less effective than NSAIDs, but superior to placebo
24
Q
NSAIDs for migraine (MOA, role, SE, caution)
A
- Prevents inflammation in the trigeminovascular system via prostaglandin synthesis inhibition
- Role -> acute migraine tx of mild to moderate severity
- Can use alone or w/ metoclopramide 10 mg
- SE = GI (dyspepsia, N/V, diarrhea), bleed, renal, rash
- Avoid or caution in ulcer disease, gastritis/ esophagitis, renal disease, hypersensitivity
25
Acute medications to avoid in migraine
- Fiorinal -> contains butalbital (known for rebound headaches)
- Opioids for migraine -> ideal limitation is maximum of 2 days/week; lack of evidence for superiority to NSAIDs/triptans
26
What cause medication overuse headache? Which medications are low, moderate, and high risk?
- Occurs from taking too much of an acute migraine reliever medication, for too long
- Mechanisms unclear
- Low risk (used 15 or days/month) = NSAIDs, acetaminophen, ASA
- Moderate risk (used > 10 days/month) = triptans, ergotamine
- High risk (used >5-10 days/month) = opioids (~8 days), ASA/ acetaminophen/ caffeine, use of > 1 acute med
27
MOH signs and sx
- AM sx -> often either present or develops upon waking; also, poor sleep quality
- Poor acute tx response -> acute prn meds may only provide partial and/or temporary relief
- Overuse of acute meds (>3 months)
- 15 or more headache days per month (often daily) w/ pre-existing episodic migraine
- Neck pain
- Great variability in location, quality, and associated sx between px and within a pt; can change over time
28
MOH management
- Taper down/stop the offending drug
- Watch for refractory rebound headache and withdrawal sx
- Prophylactic tx may help reduce rebound and withdrawal sx
- Renewed response to therapy usually occurs w/in 2 months of medication withdrawal (earliest 1-2 weeks)
29
Acute migraine tx algorithm
- Mild/moderate -> ASA, ibuprofen, naproxen, acetaminophen
- - Not responding -> triptans
- Incomplete relief or frequent tx failure (tried at least 3 different triptans for 3 different attacks) -> triptan + NSAID
- Not responding -> DHE + anti-nauseant
- Not responding -> acetaminophen + codeine/tramadol (max 2 days/week)
- If nausea, add either metoclopramide or domperidone
30
Acute migraine tx in pregnancy (options and what to avoid)
- Options -> non-pharms (especially in 1st trimester), acetaminophen, metoclopramide, sumatriptan (routine use not recommended)
- Avoid -> ASA, NSAIDs, prochlorperazine, ergotamines
31
Acute migraine tx in breastfeeding (options and what to avoid)
- Options -> acetaminophen, NSAIDs (ibuprofen preferred), metoclopramide/ domperidone/ dimenhydrinate/ prochlorperazine, sumatriptan
- Avoid -> ASA, codeine (especially if mother is UM), high-dose opioids
32
When to consider prophylaxic tx for migraine
- Frequent and/or long-lasting and/or severely debilitating migraines
- Contraindication to acute therapies
- Failure of acute therapy (either poor efficacy and/or intolerable SEs)
- > 2 attacks per week (risk of MOH)
33
Prophylactic tx for migraine
- Probability of success w/ any one of the preventative drugs is 50-75% (success = 50% or greater reduction in h/a frequency)
- Goals -> reduce attack frequency by at least 50% and reduce severity, reduce associated disability, prevent transition from acute to chronic migraine
- May increase effectiveness/response of acute migraine tx
34
Evidence-based medications for migraine prophylaxis
- Beta blockers (metoprolol, propranolol, and timolol)
- Antidepressants (amitriptyline and venlafaxine)
- Anti-epileptics (valproate and topiramate)
- Alternatives = CCBs (verapamil, flunarizine), ACEi/ARB (candesartan, lisinopril), butterbur
35
Beta blockers for migraine (role, SE, CI)
- Raises migraine threshold by modulating adrenergic system and 5-HT transmission in cortical pathways of brain
- First line (especially in px < 60 y/o, HTN, or CVD)
- Propranolol, metoprolol, and timolol have the most evidence
- Beta blockers w/ intrinsic sympathomimetic activity (pindolol, acebutolol) may not be effective
- SE = bradycardia, fatigue, hypotension, vivid dreams, depression
- CI = asthma, heart block, uncompensated HF, peripheral vascular disease
36
Antidepressants for migraine (role, SE, CI)
- Consider in those w/ comorbidities (depression, insomnia, neuropathic pain, tension-type h/a)
- TCAs -> amitriptyline = first line; conflicting evidence of other TCAs, but still used often in practice
- - Anticholinergic (avoid in BPH, glaucoma), sedation (dose HS), increased appetite, weight gain, orthostatic hypotension, cardiac toxicity (slower AV conduction)
- - CI = heart block, significant CVD, urinary retention, uncontrolled glaucoma, prostate disease, mania
- SNRIs (venlafaxine) -> benefit if co-morbid anxiety/mood disorders
- - N/V, drowsiness, sexual dysfunction
- - Avoid in HTN, kidney failure
- - Monitor for serotonin syndrome especially if also on triptan
37
Anticonvulsant drugs for migraine (role, which ones to use)
- Role -> 2nd line for prophylaxis of severe migraine
- - Px w/ seizure disorder, anxiety, bipolar disorder
- Valproic acid and topiramate have most evidence
- - Valproate = effective; CI in pregnancy
- - Topiramate = effective; titrate slowly from 15-25 mg daily up to 100-200 mg daily (b/c of rash?); category D in pregnancy
- Gabapentin has moderate quality evidence for efficacy
- - Generally, well tolerated but somnolence is common
38
Anticonvulsant drugs – safety
- Valproic acid -> N/V, tremor, alopecia, weight gain, hepatotoxicity (rare)
- - Avoid in liver disease, bleeding disorders, pregnancy, obesity
- Topiramate -> paresthesia, fatigue, anorexia, diarrhea, weight loss, memory impairment
- - Avoid in px w/ hx of kidney stones/failure, pregnancy, cognitive impairment, angle closure glaucoma
- Gabapentin -> mild/transient somnolence, dizziness, tremor, ataxia
39
Principles of prophylactic management of migraine
- Start low and titrate slowly (to maximal dose, efficacy or to intolerable SE)
- Trial drug for adequate period of time (delayed response) -> usually 2-3 months at target dose
- Consider pt-specific characteristics in selection of prophylactic tx
- Discuss expected benefits w/ px; make sure they are aware of what a tx success looks like
- If tx failure, try drug from different therapeutic class
- Lifestyle measures are a very important part of therapy
40
Migraine prophylactic tx algorithm
- 1st time prophylaxis -> propranolol, nadolol, metoprolol, amitriptyline, venlafaxine
- Not responding -> try different class
- Refractory -> specialist referral; combination beta blocker w/ topiramate or VPA or TCA; topiramate w/ TCA
41
Pt specific factors when considering migraine prophylactic tx
- High BMI -> topiramate
- HTN -> beta blocker, candesartan, lisinopril
- Mood/anxiety -> amitriptyline (nortriptyline), venlafaxine
- Pregnant -> non-pharms, magnesium, propranolol/ metoprolol, amitriptyline (nortriptyline)
- Lactation -> non-pharms, magnesium, propranolol/ nadolol/ metoprolol, amitriptyline (nortriptyline), valproate
42
What are CGRP antagonists? Advantages, disadvantages, SE?
- MAb for preventative tx of migraine
- Target calcitonin gene-related peptide (CGRP) which is a vasodilatory neuropeptide w/ role in migraine
- Don’t appear to have greater efficacy than other prophylactic tx
- Advantages -> once monthly injection, well tolerated, specific targets (low risk of Dis)
- Disadvantages -> no long-term safety data, increased stroke/MI risk?
- Erenumab SE = constipation, Ab development, injection site reaction
- Strongly consider for px w/ severe disability and lack of benefit from or unable to tolerate existing alternatives, difficulty adhering to daily medication regimens, polypharmacy
- Caution in px who are concomitantly exposed to vasoconstrictive drugs or substances (CGRP blockade may be risky)
