Headache Disorders 2

Question 1

evidence comparison for migraine meds

Answer 1

triptran = other triptans
ASA, NSAID = triptans in trials
ASA, NSAD < triptans in clin practice
ergotamine/caffeine<triptans
suma 50 + naprox 500mg > either alone
ASA = acetaminophen + codeine

Question 2

OTHER LINES OF THERAPY
v Ergot derivatives

Answer 2

 Non-selective 5-HT receptor agonists
 Also, they have effects on alpha, beta adrenergic and dopaminergic
receptors
 The non-selectivity is responsible for their many side effects and
limiting their use
 Adverse effects:
 Nausea and vomiting (very common, and so antiemetics are given prior
to iv dose)
 Chest discomfort
 Fatigue, dizziness, drowsiness
 Cramps
 Paresthesia
 Vasoconstriction

Question 3

OTHER LINES OF THERAPY
v Ergot derivatives contra

Answer 3

Contraindications:
 Ischemic heart disease
 Uncontrolled hypertension
 Pregnancy
 Renal or liver disease
 Co-administration with triptans
 Co-administration with CYP3A4 inhibitors

Renal or liver disease because of the reduced metabolism and elimination. And co-administration was triptans because both are vasoconstrictors. And co-administration of CYP 3A4 inhibitors because they are metabolized by those enzymes. T

Question 4

 Dihydroergotamine (DHE)

Answer 4

Intranasal and parenteral
 The iv-route is reserved for severe resistant headache
 metoclopramide 10 mg iv or prochlorperazine 5 mg iv can be given as
pre iv

we use that in the emergency department. And you need to give metoclopramide as prokinetic anti-nausea
2 reasons: avoid the side effects of the ergotamine. And at the same time, metoclopramide could work as an abortive therapy for migraine.

Question 5

OTHER TREATMENT MODALITIES
 Antinauseants and prokinetics

Answer 5

 In headache disorders associated with nausea and vomiting
 Metoclopramide iv is also used an abortive agent in ED
 May facilitate absorption of headache drugs
 Alternatives:
 Metoclopramide 10 mg po or iv (strongest evidence)
 Prochloperazine
 Domperidone 10 mg po
 Dimenhydrinate 50 to 100 mg po

Question 6

LAST LINES – AVOID ROUTINE USE
Opioids

Answer 6

Codeine or Tramadol combination analgesics
Could be used when NSAIDS and triptans are
contraindicated or poorly tolerated
Or as rescue medications
Butorphanol nasal spray
To avoid the risk of dependence, opioids should
be reserved for moderate to severe headache that
is infrequent and in patients to whom
conventional therapy is contraindicated
Butalbital-containing combination analgesics

Question 7

CALCITONIN GENE-RELATED PEPTIDE RECEPTOR
ANTAGONISTS (GEPANTS)

Answer 7

 For the Acute Treatment of Migraine
 Ubrogepant (Ubrelvy®)
 Rimegepant (Nurtec ODT®) – (Not yet in Canada)
 Both effective within 2h in moderate to severe migraine (pain and
associated symptoms)
 No direct comparison to other abortive agents.

calcitonin gene related peptide, It’s actually it’s a nociceptor transmitter. It actually can call responsible for pain transmission and it’s released in migraine and causes vasodilatipm.
This could be the proposed mechanism for migraine and could cause systemic like say, neurogenic inflammation.

Sumatriptan or triptans in general, when the work they worked in the serotonin receptors, they reduce neurogenic inflammation and for some time the actual also the reduced the level of calcitonin gene related peptide. So based on this mechanism, say what if we decide to have an antibody against that order receptor antagonist?

Question 8

DITANS

Answer 8

 For the Acute Treatment of Migraine – (Not yet in Canada)
 5HT-1F receptor agonist
 Lasmiditan (Reyvow®)
 Both effective within 2h in moderate to severe migraine
 ADR: temporary driving impairment (no driving for 8h post
dose)

very selective serotonin receptor agonist. It works similar to the triptans. However, it devoid of the vasoconstrictor effect. Oh, this is a big plus is not vasoconstrictor.

Question 9

Which agent would you choose for a
female patient with migraine and:
 It is severe enough to limit daily activity
Pregnant
Peptic ulcer disease
Previous stroke
Gout
On citalopram 40 mg po daily for depressio

Answer 9

Severe enoguh:
- Sumatriptan; severe enough to use stratified approach
Pregnant: Sumatriptan
- Won’t start right away
- Use Tylenol first
- don’t use any other triptans. Because we don’t we don’t have any evidence.

Peptic ulcer disease.
- Can you use Tylenol, acetaminophen, right
- can use sumatriptan or any triptan
Previous stroke
- no to All the vasoconstrictors, triptans, ergot derivatives
Gout
-can use anything

Citalopram
- acetaminophen, NSAID
Triptan, you can use but you need to monitor for serotonin syndrome. They are not absolutely contraindicated unless the patient on seven serotonergic agents that increase serotonin,

Question 10

MIGRAINE PROPHYLAXIS

Answer 10

When?
The attacks are severe enough to limit the usual
daily activity of the patient
Headache is so frequent
Three or more attacks per month that are resistant
to therapy
Migraine medications are contraindicated or failed

Beta blockers
 First-line agents
 Examples: Metoprolol, Propranolol and Timolol
 Adverse effects: hypotension, bradycardia,
bronchospasm, depression, insomnia

Calcium channel Blockers
They act by modulating neurotransmitters function
 Flunarizine: the most effective CCB but complicated
with EPS, depression and weight gain
Verapamil: less effective than flunarizine but better
tolerated. SE: Constipation, dizziness (limited
evidence)

BBit’s complicated by extrapyramidal symptoms. Depression, weight gain.

verapamil: similar to some of the other calcium channel blockers, one of the major side effects, constipation

Question 11

migraine prophylaxis other agents

Answer 11

 ACE inhibitors/ARBs
 Lisinopril
Candesartan
There’s also a strong good evidence for ACE inhibitors, lisinopril , candesartan can be used

 Tricyclic antidepressants
 They act as analgesics in doses less than those used in
depression
 Amitriptyline
 Weak evidence for other TCAs
 nortriptyline
 Anticholinergic side effects, sedation
it’s preferred to be taken at night. Why? Because you’re sedating drugs. So looking at night and good sleep,

 Antiseizure Medications
 Topiramate: Topiramate strongest evidence out of the anti-seizure meds to do my migraines for migraine prophylaxis.
if you take lots of it right away, it has cognitive side effects. Some people will get like really drowsy and affect their cognitive concentration.
 Slow dose titration is recommended
 Valproic acid
 Gabapentin

BB are more benign agents than other; strong evidence
Valproic acid: Although it’s strong evidence for migraine prophylaxis, the weak recommendation strands because they are nasty drugs and side effects
Botox actually has evidenced for chronic migraine.

Question 12

CALCITONIN GENE-RELATED PEPTIDE (CGRP)
ANTIBODY

Answer 12

 Erenumab (Aimovig®)
 Fremanezumab (Ajovy®)
 Galcanezumab (Emgality®)
 Eptinezumab (Vyepti®)
 Indication: Migraine Prophylaxis

stay in the body for a long time because antibodies are proteins and Locker IVIG or something, they have stayed in the body for weeks. That’s why it could be used for prophylaxis. They are recently, recently approved

because they are antibodies, they are not available as oral medication. All of them are injectables, either subcutaneous or intravenous medications. But good news they are taking like every month or every two months.

Question 13

MIGRAINE PROPHYLAXIS
Initiate LOW and go SLOW

Answer 13

 Success defined by 50% reduction in headache frequency
 If headache occurs in a pattern e.g. menstrual cycle give
NSAIDs at the time of the incident
 If the patient is healthy or with hypertension, IHD give beta
blockers
 CCBs or ARBs/ACEIs if beta blockers are contraindicated
 If patient with depression or insomnia give TCAs

 If patient with seizure disorder or with bipolar disorder give
an antiseizure medication
 If other agents are ineffective use drug combination or other
treatment alternatives such as cGRP antibodies or Pizotifen
 If any of the recommended agents are CI or failed, with
adequate trial period at target dose for 2 months, try the
therapy in the next priority

Question 14

MIGRAINE IN EMERGENCY DEPARTMENT

Answer 14

What agents?
 Sumatriptan SC
 Metoclopramide IV
 Prochlorperazine IV
 Opioids
 DHE
 Meperidine
 Ketorolac
 Corticosteroids
 IV dexamethasone 6-10 mg
 Associated with reduced headache recurrence for up to 3 days

Ketorolac: it is the only NSAID available as parenteral here,

Question 15

CLUSTER HEADACHE - MANAGEMENT

Answer 15

 Abortive Therapy
 Challenged by its short lived nature that makes oral
therapy useless

 Prophylaxis
 Used to control a cluster period and produces remission
by the time you take oral medication, by the time it kicks in, it’s already gone. So most patients cluster headache would benefit from prophylaxis. Sometimes we do some sort of a transitional prophylaxis and give a short period of steroids until the chronic prophylaxis kicks in

 Surgical intervention
 For refractory cluster headache
 Nerve radio frequency ablation
 Neurostimulation (e.g. deep brain stimulation, occipital
nerve stimulation)

Question 16

CLUSTER HA- ABORTIVE THERAPY

Answer 16

 First line: O2, Sumatriptan S.C., intranasal Zolmitriptan
 Oxygen
 7 L/min (up to 12 L/min) of 100% O2 for 15 min via high
flow mask
 80% of patients respond in 30 min
 Mechanism of action is unknown
 No adverse effects
 Requires bulky equipment

Question 17

CLUSTER HA- ABORTIVE THERAPY
in addition to O2 tx?

Answer 17

 Sumatriptan SC
 The most effective abortive agent
 75% of patients respond within 20 min
 6 mg SC injection, higher doses are no more effective.
 Zolmitriptan nasal spray
 5 mg (1 spray)
 Effective within 30 min
 Sumatriptan nasal spray – 2nd - line
 20 mg (1 spray) – less effective than the SC form
 Others: intranasal lidocaine, oral zolmitriptan, sc
octreotide

Question 18

CLUSTER HEADACHE
PROPHYLAXIS

Answer 18

 Verapamil
 The drug of choice
 240-960 mg/d
 Well tolerated, safe and effective
 SE: constipation, bradycardia, hypotension at higher doses

 Lithium
 Second line when verapamil is contraindicated or ineffective
 Dose 900-1200 mg/d (target 0.6-1.2 mmol/L)

 Topiramate 25 mg/day – target at least 100 mg/d
 Melatonin 10 mg qhs
 Others: valproate, capsaicin intranasal, topiramate,
gabapentin, baclofen, prednisone (short term)

Question 19

MEDICATION-OVERUSE HEADACHE
(MOH)

Answer 19

 Epidemiology
 Prevalence = 1-1.4% in the general population
 Highest rate is women in their 50’s; prevalence of 5%
 More commonly associated with barbiturate and opioid use
But now it’s reported for all the analgesics, all the triptans, and the other agents for pain control.

 Diagnostic Criteria
A. Headache present on ≥15 days/month AND
B. Regular overuse for ≥3 months of one or more acute/symptomatic
treatment drugs (The abortive agents)
A. 10 days or more for opioids
B. 15 days or more for Tylenol, NSAIDs

C. Headache has developed or markedly worsened during medication
overuse

Question 20

MEDICATION-OVERUSE HEADACHE
(MOH)

treatment

Answer 20

 Treatment
 Patient education
 Stop/taper headache medications.
 Try prophylactic therapy
 If headache worsens may get iv DHE (Raskin protocol)
 After control, limit the use of headache medications
 Role of the pharmacist?

Question 21

SPECIAL POPULATIONS
 Pure menstrual migraine, or menstrually-associated migraine

Answer 21

 Use triptan BID starting 2 days prior to onset of menses, continuing
for 5-7 days
 Frovatriptan 2.5 mg po BID
 Naratriptan 1 mg po BID
 Administer NSAID BID e.g. Naproxen on a standing basis 2 days
prior to onset of menses, continuing for 5-6 days
 Other options:
 Supplementing estrogen around the menstrual period
 Risk of relapse after stopping the therapy
 Use of OCs without interruption
 Consider the risk of continued hormonal therapy and avoid in migraine with auras,
smokers, focal neurologic symptoms, age > 35 (risk of stroke)

Question 22

 Pregnancy

Answer 22

 Focus on nutrition, non-pharmacologic interventions
 TTH – approx. 30% report improvement
 Treat with analgesics, acetaminophen preferred
 Migraine – approx. 65% report improvement
 Acute: analgesics; possibly sumatriptan
 Prophylaxis: low-dose propranolol; Mg; possibly amitriptyline
 Cluster – few studies in pregnant women
 Acute: Treat with oxygen
 Alternatives: SC or intranasal sumatriptan for acute treatment
 Prophylaxis: Verapamil or prednisone; gabapentin as alternative

. Many of the pregnant women report improvement in their headaches. Most likely, probably because of the increase hormonal levels
- Tylenol
- Generally, first trimesters, if you can avoid all the drugs in the world, that will be the best, right?
- The third trimester, I, nsaids are not recommended because especially like closer to delivery tool because they cause premature closure of something called patent ductus arteriosus.
2nd trimester is ok?

Question 23

 Pregnancy - Summary

Answer 23

Non-pharm
 Acetaminophen
 Ibuprofen, naproxen (avoid indomethacin; avoid NSAIDs in 3rd
trimester)
 If have to, codeine combinations – avoid near term
 Avoid Ergots, barbiturates, valproic acid, topiramate, triptan
(possible exception: sumatriptan)
 Refer if new onset headache to rule out serious causes e.g.
eclampsia
new onset headache during pregnancy, she needs to get checked. You need to refer the patient because the medial could be preeclampsia, eclampsia

Question 24

Lactation

Answer 24

Non-pharm measures
Acetaminophen, ibuprofen
Avoid: ergots, barbiturates and opioids
Sumatriptan could be used (more data than other
agents) – but avoid in the immediate post partum
period
Prophylaxis: propranolol, magnesium; VPA

Question 25

MONITORING HEADACHE DISORDERS

Answer 25

Advise patient to keep a headache calendar
Headache severity
Associated symptoms
 Frequency of headache
Adverse reactions
 Efficacy of certain agents
Record use of headache medications