Migraines & Headache Flashcards
Describe a simplified pathophysiology of migraines.
- some people have sensitized neurons (unclear)
- a migraine trigger comes along
- brain releases potent vasodilators (CGRP, NO) and inflammation reactions
- vasodilation=big pain; inflammation begets more inflammation
What is the MOA of triptans?
selective serotonin agonists = vasoconstrictors
What is the MOA of NSAIDs?
anti-inflammation
What is the MOA of anti-CGRP drugs?
prevent/reduce vasodilation
What is critical with migraine treatment in regards to the timing of treatment?
early treatment=nip it in the bud=better efficacy
-hitting inflammation early is critical
What is migraine aura?
early warning sign of migraine
What percentage of people with migraines experience aura?
30%
What are the symptoms of aura?
visual aura (90% of symptoms)
-lightning bolts, blind spots, flickering bright lines
sensory disturbances
-tingling, numbness, pins and needles
speech disturbances
-difficulty word-finding
What are some migraine triggers?
stress
meal skipping
foods
alcohol
caffeine withdrawal
dehydration
menstruation
lights/sunlight
erratic sleep/shift work
perfume/odour
obesity
change in barometric pressure
What is the mnemonic used to help in the diagnosis of a migraine?
POUND
-pulsatile
-one day duration(4-72h if untreated or poor treatment)
-unilateral headache
-nausea or vomiting
-disabling intensity
each one is worth 1 point
What is the likelihood of migraine based on points derived from the POUND mnemonic?
4-5 pts = 92%
3 pts = 64%
0-2 pts = 17%
Describe a simplified treatment approach to acute migraine.
- NSAID
-cheap
-response in 4-5/10 patients - triptan
-bit of a boost compared to NSAIDs
-can start here
-response in 5-6/10 patients - NSAID + triptan
-combining is better than one alone
-response in 6-7/10 patients - subcutaneous sumatriptan
-can start here if really bad migraines
-response in 8/10 patients - refractory patients
-manage agent failure
-try alt combinations (acet, NSAIDs, triptans, metoclopramide, caffeine)
-start migraine prophylaxis
-possibly try DHE nasal spray
What is “response” defined as for acute migraines?
pain relief at 2 hours
-placebo response is 2-3/10 patients
Which agent has the fastest onset for acute migraine?
subcutaneous sumatriptan
Which drugs should be avoided in acute migraine?
opioids and barbiturates
-risk of MOH, AE, and overdose
-not doing anything for inflammation
-2x as likely to cause MOH
Which agent can be added anywhere along the treatment approach to acute migraine to improve efficacy and decrease nausea?
metoclopramide
-anti emetic by speeding up GIT motility
-faster absorption of other drugs
What is the DHE nasal spray?
dihydro ergotamine
-hits 5HT receptors but dirtier (more AE)
-almost never used
How can we manage NSAID failure for acute migraine?
ensure NSAID is taken at earliest onset of migraine pain and on an empty stomach (food delays onset)
try a faster-acting NSAID formulation (10-20 min faster than regular tabs)
-naproxen sodium, ibuprofen liquid gels, diclofenac potassium
Differentiate naproxen sodium and naproxen base.
naproxen sodium is 20-30min faster than naproxen base
-sodium of choice for migraine
What are the benefits of migraine prophylaxis?
decrease intensity of migraines and less migraines
decreasing intensity helps boost efficacy of other drugs
How can we manage triptan failure for acute migraine?
ensure triptan is taken at earliest onset of migraine pain
switch to a different triptan
-try for at least 3 different migraines (not a class response)
add acetaminophen, NSAID, or metoclopramide
ensure adequate absorption
-switch to injectable or nasal spray if vomiting dose
fast-acting triptan often preferred but if tolerability concerns then try slow-onset triptan
What are the slow-onset triptans?
naratriptan
frovatriptan
What are the fast-acting triptans?
eletriptan
almotriptan
rizatriptan
sumatriptan
zolmitriptan
Why should Tylenol #3 be avoided for migraines in almost every patient?
opioids have double the risk of MOH
caffeine dose is subtherapeutic
-~100mg needed for migraine efficacy, T3 has 15mg
acetaminophen dose is often subtherapeutic
-1000mg has best evidence, would need T3 x 3
codeine metabolism is unpredictable
What are the side effects and contraindications of triptans?
triptans are potent vasoconstrictors
-chest discomfort/tightness, palpitations, dizziness, flushing
-CI in CV disease (uncontrolled HTN, previous stroke/MI, etc)
-CI within 24h of ergots due to coronary vasospasm; do not combine triptans
triptans are potent 5HT agonists
-nausea
-CI with MAOI (serotonin syndrome) and caution with other serotonergic drugs (increase monitoring)
What are some considerations when deciding which triptan is best for your patient?
fastest relief: 10-15min with SC or nasal
best efficacy at 2hr: SC suma
-lowest efficacy at 2hr: nara or frova
best tolerability: slow onset or nara or frova decreases AE or nausea
best if long-lasting attacks: nara or frova
best for privacy: ODT (no H20)
lower cost: almo po
useful if vomiting: SC or nasal or add antiemetic
True or false: all triptans have similar safety in hepatic and renal disease
false
Which triptan has the highest efficacy?
SC sumatriptan
-works in up to 80% of patients
-useful if vomiting/severe nausea with oral agents
-guarantee absorption
What are some tips and tricks for acute migraines?
try a triptan for at least 3 migraines before giving up and try at least 3 triptans before giving up on the class
acetaminophen alone or in combo can be helpful
-overall less powerful than NSAIDs
N/V is common with migraines
-ODT, antiemetic, intranasal, injectable = all useful
True or false: ODT triptans are faster than regular tabs
false
they are not buccal, absorbed in the intestine
useful if water causes nausea
What is the max days per month of acute meds to help avoid MOH?
opioids: 9 days
triptans: 9 days
NSAIDs or acet: 14 days
multiple classes: 9 days
What is menstrual migraine?
for some, migraines increase during menstruation
What are the options for pre-treatment of menstrual migraine?
start ~2 days before treatment
-naproxen 500mg BID x ~6 days
-frovatriptan 2.5mg BID x ~6 days
-naratriptan 1mg BID x ~6 days
-estradiol gel 1.5mg daily x 7 days
option for prevention with continuous CHC
-but CHC + migraine with aura = CI
What are the available anti-CGRP drugs?
ubrogepant
-treatment dose: 50-100mg stat
rimegepant and zavegepant (USA)
atogepant approved for prevention
-10-60mg daily
What are the adverse effects of the anti-CGRP drugs?
nausea
somnolence
What are the benefits of the anti-CGRP drugs?
not CI in CV disease
very low risk of MOH
What is a con of the anti-CGRP drugs?
not as effective for acute migraine
-although not compared head to head
Who should consider utilizing migraine prophylaxis?
patient preference
-patient prefers prophylaxis for any reason
frequent attacks
-e.g. > 6 headache days/month
severely disabling attacks
-especially if > 3/month
difficult-to-treat attacks
-acute tx doesnt work well, is CI, or causes problems
Describe the steps in setting up an adequate trial for migraine prophylaxis.
- initiate a headache diary
- start a migraine prevention drug at a low dose
- increase dose gradually q1-2wks guided by target dose range, patient response and tolerability
- remain at that dose for ~8-12wks to assess effectiveness and tolerability
- assess and decide whether to continue, increase the dose, or taper/dc
Which agents have the best efficacy data for migraine prophylaxis?
amitriptyline 50-75mg/d hs
propranolol 80-160mg/d
metoprolol 100-200mg/d
topiramate 100mg/d
Which agents for migraine prophylaxis have the fewest adverse effects?
candesartan 16mg/d
magnesium 500-600mg/d
riboflavin 400mg/d
Which agent might be tried for migraine prophylaxis if the patient wants to pursue smoking cessation?
nortriptyline
Which agent might be tried for migraine prophylaxis if the patient experiences insomnia?
amitriptyline
Which agent might be tried for migraine prophylaxis if the patient has hypertension?
beta-blocker
candesartan
lisinopril
verapamil
Which agent might be tried for migraine prophylaxis if the patient has chronic pain?
amitriptyline
venlafaxine
duloxetine
topiramate
possibly gabapentin
Which agent might be tried for migraine prophylaxis if the patient has depression or anxiety?
venlafaxine
duloxetine
amitriptyline
What are some tips and tricks for migraine prophylaxis?
set realistic expectations
-decrease in migraine days/month by >50%; less severe headaches
use a headache diary
-watch for triggers & track medication effectiveness + tolerability
be patient: allow time to stabilize on an effective dose
-effectiveness increases with time
-tolerability improves with time
help manage side effects
What are the next steps if a trial of migraine prophylaxis fails?
consider:
-another drug class
-combo therapy
-a CGRP antagonist if failure with 2 or more agents
How long should we treat at target dose before deciding if prophylaxis is helping?
8-12 weeks
Which beta-blockers are used for migraine prophylaxis and what are their target doses?
propranolol: 40-80mg BID, 80-160mg LA
metoprolol: 50-100mg BID, 100-200mg SR
timolol: 10-15mg BID
Which TCAs are used for migraine prophylaxis and what are their target doses?
amitriptyline: 50-75mg hs
nortriptyline: 50-75mg hs
Which anticonvulsants are used for migraine prophylaxis and what are their target doses?
topiramate: 50mg BID
divalproex: 500-750mg BID cc
What is a caution with anticonvulsants as migraine prophylaxis?
caution with women of child-bearing age
Which ACEI and ARBs are used for migraine prophylaxis and what are their target doses?
candesartan: 16mg daily
lisinopril: 20mg daily
Which SNRIs are used for migraine prophylaxis and what are their target doses?
venlafaxine 150mg daily
duloxetine: 60mg daily
What is the target dose of pizotifen for migraine prophylaxis?
1.5mg hs
What is the MOA of pizotifen?
serotonin antagonist
What is an adverse effect of pizotifen?
very sedating
Which CCBs are used for migraine prophylaxis and what are their target doses?
flunarazine: 10mg hs
verapamil: 240mg daily with food
Which herbals are used for migraine prophylaxis and what are their target doses?
magnesium oxide: 500mg elemental daily
magnesium citrate: 300mg BID
riboflavin: 400mg daily
What is an adverse effect of high dose riboflavin?
neon-yellow urine
What are the anti-CGRPs used for migraine prophylaxis?
fremanezumab: 225mg SC q4wk or 675mg SC q12wk
eptinezumab
erenumab
galcanezumab
atogepant
rimegepant
What are some “other” drugs used for migraine prophylaxis?
memantine: 10mg hs
Botox: maybe if > 15 migraine days/month
What is a critical drug interaction of propranolol with respect to migraines?
slows metabolism of rizatriptan and thus levels increase 70%
How can we manage the propranolol-rizatriptan drug interaction?
use 5mg rizatriptan tabs instead of 10mg
change triptans
change beta-blockers
What is the MOA of the CGRP MABs?
MAB targeting calcitonin gene-related peptide
What is the response rate of the CGRP MABs?
40% of patients
Which CGRP MAB is covered by Sask and NIHB?
fremanezumab
-failed two po prophylactic agents
How frequently is fremenazeumab dosed?
can be given q3mo but prefer monthly (better Css)
What are the adverse effects of CGRP MABs?
injection site rxn
hypertension
What are the red flags of acute headache?
emergency (call for ambulance)
-worst HA
-impaired speech, strength, sensation, consciousness
-neck stiffness or fever
-thunderclap HA
-head trauma
-eye symptoms
urgent (send for referral)
-first ever headache
-headache with exercise or sex
-new headache if age >50 yrs
-HIV, cancer, lyme dx, pregnancy
-papilledema
-older adult with cognitive changes
What are the different types of headaches?
migraine
tension type
cluster
Describe migraines based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis
duration: 4-72h
location: typically unilateral (but 40% bilateral)
pain: pulsating, mod-severe
sx: N/V, photophobia, phonophobia, aura (5-60min), triggers
acute tx: NSAIDs, acet, triptan, anti-emetic, DHE
prophylaxis: BB, TCA, topiramate, candesartan, herbs, anti-CGRP, venlafaxine
Describe tension type headache based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis
duration: 30min-7d
location: typically bilateral
pain: photo or phonophobia, NO N/V, not usually triggered by routine activity
acute tx: NSAIDs, acet
prophylaxis: TCA
Differentiate frequent and infrequent TTH.
infrequent: < 1 day/month average
frequent: 1-14 days/month average
Describe cluster headache based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis
duration: 15min-3h (untreated)
location: unilateral, orbital, supraorbital, temporal, combo
pain: stabbing, nonpulsating, severe to excruciating
sx: clusters qod up to 8 HA/d, ipsilateral, nasal, eye, sweating, restlessness
acute tx: SC sumatriptan
prophylaxis: verapamil (240-960mg/d)
Differentiate episodic and chronic cluster headache.
episodic: 2 cluster periods lasting 7-365d, remissions of >1 month
chronic: episodes recur for >1 year without remission or with remission lasting < 1 month
What is MOH?
chronic HA caused by the overuse of acute HA medication that often provides inadequate pain relief
- > 15 HA days/month
-common to wake up with a daily HA
What causes MOH?
> 9 days/month of triptans or opioids
14 days/month of NSAIDs or acet
9 days/month of combo
How can we break the cycle of MOH?
recognize MOH
stop the overused med
create a prevention and treatment plan to avoid relapse
How is MOH treated?
stopping the overused medication
stop or taper the overused med while starting a prophylactic med
start prophylactic med only
What is considered resolution of MOH?
return to episodic headaches ( < 15 days/month)
-allow 3 months to establish new baseline
What are some tips and tricks for treating MOH?
educate all patients on risk of MOH
prophylactic meds may become more effective once the overused med is stopped
headache diaries
non-drug approaches
What are the withdrawal symptoms of MOH?
HA will increase in pain and frequency before they improve
anxiety, NV, sleep issues
generally last 2-10 days but can be up to 2-4wks
meaningful improvement in HA frequency usually 4-8wks
