Migraines and Headache Flashcards
Primary Headaches
- Tension headache
- Cluster headache
- Migraine
- With aura
- W/o aura
Secondary Headaches
- Head/neck trauma
- Vascular disorders (CVA)
- Non-vascular disorders (seizure, tumor)
- Substance withdrawal
- Medication overuse headache (MOH)
- Infection
- Psychiatric disorder
Depolarization Theory
Activation of trigeminal nerve system
* Vasoactive neuropeptide release (calcitonin gene-related peptide (CGRP), neurokinin A, substance P)
* Cortical spreading depression: neuropeptides interact with dural blood vessels–> promotes vasodilation–> neurogenic inflammation–> activation of sensory neurons in trigeminal nerve–> pain
What are some food triggers of migraine?
- Alcohol
- Caffeine/caffeine withdrawal
- Chocolate
- MSG
- Nitrate-containing foods
- Tyramine-containing foods
- Yeast products
What are some environmental triggers of migraine?
- Glare or flickering lights
- High altitude
- Loud noises
- Strong smells/fumes
- Tobacco smoke
- Weather changes
What are some behavioral-physiological triggers of migraine?
- Excess or insufficient sleep
- Fatigue
- Menstruation, menopause
- Skipped meals
- Strenuous physical activity
- Stress or post-stress
Premonitory phase
- Previously referred to as prodrome and/or warning symptoms
- Experienced by up to 80% of patients
- Occurs hours-days before onset of migraine
What are some symptoms of the premonitory phase?
- Allodynia, phonophobia, photophobia, hypersomnia, difficulty concentrating
- Anxiety, depression, euphoria, drowsiness, fatigue, hyperactivity, restlessness
- Polyuria, diarrhea, constipation
- Stiff neck, yawning, thirst, food cravings, anorexia
What are some visual symptoms of an aura?
Positive features: scintillating scotomas, fortification spectrum (flashes, diverging lines, zig zagging lines)
What are some sensory and motor symptoms of an aura?
Sensory: Paresthesia
Motor: Dysphasia, weakness, aphasia, hemiparesis
Postdrome phase
- Fatigue, irritability, impaired concentration, mood changes
- Some patients report mild euphoria or feeling unusually refreshed
- Sudden head movement may precipitate pain
What are the diagnostic criteria of a migraine without aura?
≥ 5 attacks meeting all the following criteria:
* Headache 4-72 hours (when untreated or unsuccessfully treated)
* Not better accounted for by another ICHD-3 diagnosis
Headaches with ≥ 2 of the following characteristics:
* Location: unilateral
* Quality: pulsating
* Intensity: moderate or severe
* Aggravation by or causing avoidance of physical activity (e.g., walking or climbing stairs)
AND
Headache with ≥ 1 of the following symptoms
* Nausea and/or vomiting
* Photophobia and phonophobia
SULTANS
What is the diagnostic criteria for migraines with an aura?
≥ 2 attacks with the following criteria
* Not better accounted for by another ICHD-3 diagnosis
* ≥ 1 fully reversible aura symptoms:
- Visual
- Sensory
- Speech and/or language
- Motor
- Brain stem
- Retinal
AND
* ≥ 3 characteristics
- ≥ 1 aura symptoms spreads gradually over ≥ 5 minutes
- ≥ 2 aura symptoms occur in succession
- ≥ 1 aura symptoms is unilateral
- ≥ 1 aura symptoms is positive
- Aura is accompanies or followed within 60 minutes by headache
What are some concerning symptoms?
- Systemic s/sx (fever, myalgias, weight loss)
- Neurologic s/sx (confusion, AMS)
- Onset (sudden, abrupt, split second)
- Older patient with new onset (> 40-50 yo)
- Pattern change (new or different? Frequency? Sx?)
- Secondary risk factors (HIV, systemic cancer)
What are some migraine symptom assessment tools?
- Migraine Disability Assessment (MIDAS) Test
- Headache Impact Test (HIT-6)
What is the MOA of analgesics?
Prevent neurogenic inflammation in trigeminovascular system by inhibiting prostaglandins
What is the place of therapy of analgesics?
- First line for mild-moderate symptoms
- Second line: combination products
What are some clinical pearls of analgesics?
- Limit to 3 days/week or 15 days/month to prevent MOH (medication overuse headache)
- Avoid butalbital-containing products due to abuse potential
- Acetaminophen/butalbital/caffeine (Fioricet)
- Aspirin/butalbital/caffeine (Fiorinal)
What are adverse effects of analgesics?
NSAIDS:
-Cardiovascular: blood pressure elevation
-Gastrointestinal (GI)
* Short term: dyspepsia
* Long term: GI bleed or ulceration
Renal: Injury with short- or long-term use
APAP: Hepatic injury at elevated doses
Aspirin: Tinnitus, GI bleed or ulceration
What is the MOA of triptans?
Selective agonist at 5-HT1B and 5-HT1D (serotonin) receptors
* 5-HT1B mediated vasoconstriction of cerebral blood vessels
* Stimulation of presynaptic 5-HT1D inhibits release of vasoactive neuropeptides (CGRP, substance P) from perivascular trigeminal neurons
* Stimulation of 5-HT1D receptors in brain stem trigeminal nuclei disrupts pain signal transmission
What is the place of therapy of Triptans?
- Severe migraines: first-line
- Mild-moderate migraines: unresponsive to combination analgesics
Which triptans have the most favorable outcomes?
- Sumatriptan SQ injection
- Rizatriptan ODT
- Zolmitriptan ODT
- Eletriptan tablets
What are some clinical pearls of triptans?
Large inter-patient variability:
* If unsuccessful treatment of 3 attacks with one triptan – try a different triptan
* Can consider different med class after 2 failed triptans
Effective, well-tolerated:
* If administered within 4 hours of migraine onset – preferably within the 1st hour
* Increased sustained pain-free response when combined with NSAIDs compared to either drug alone
- Best studied Triptan/NSAID combo: sumatriptan + naproxen (Treximet)
- Limit use < 3 days/week, < 10 days/month to prevent MOH
What are the contraindications of Triptans?
- Cerebrovascular disease: Stroke, TIA
- Ischemic Heart Disease
- Cardiovascular: Uncontrolled HTN, ischemic heart disease
- Hemiplegic or basilar migraine
What are some drug interactions of triptans?
- SSRI/SNRI: Serotonin syndrome
(rare; monitor if co-prescribed) - Ergot derivative/other triptan within 24 hours (prolonged vasospastic reaction
- MAOI administration within 2 weeks (everything is contraindicated but use caution with Almotriptan)
- CYP3A4 inhibitors
- Propranolol (causes INCREASED concentrations of triptans)
- Cimetidine (limit zolmitriptan to 2.5 mg or 5 mg/day)
What are some ADE of triptans?
- Dizziness, fatigue, flushing, paresthesias, nausea, vomiting
- Local injection site inflammation
- Taste perversion
- Nasal discomfort (following nasal administration)
- Angina/coronary ischemia
What is the MOA of Ergot Alkaloid?
Nonselective 5-HT1 agonists
* Constrict intracranial blood vessels
* Inhibit neurogenic inflammation in trigeminovascular system
Activate other types of serotonin receptors, alpha-adrenergic, and dopamine receptors
Both venous and arterial constriction occur with therapeutic doses
* Ergotamine tartrate exerts more potent artery vasoconstriction
* Dihydroergotamine exerts more potent venoconstriction
What is the place of therapy of Ergot alkaloids?
- Treat moderate to severe migraines
- Patients failing triptans
What are the effective routes of administration of ergot alkaloids?
- IV> IM» Inhaled > Sublingual > Oral
- GI absorption is erratic
What are the contraindications of ergot alkaloids?
- Pregnancy or breastfeeding
- Cardiovascular: Uncontrolled HTN, peripheral vascular disease, ischemic heart disease, coronary vascular disease
- Impaired renal/hepatic function
- Hemiplegic or basilar migraine
What are the drug interactions of ergot alkaloids?
- Concurrent use with CYP3A4 inhibitors (CONTRAINDICATED)
- Concurrent use with vasoconstrictors, including triptans (CONTRAINDICATIONS)
What are the ADE of triptans?
Common:
* Nausea, vomiting, muscle cramps, abdominal pain, numbness/tingling in fingers and toes
Serious:
* Sustained generalized vasoconstriction
* HTN, MI, CVA, gangrene, bowel ischemia, coronary ischemia
What is the MOA of CGRP Receptor Antagonists?
- Decreases activity of CGRP
- Lacks direct vasoconstrictive activity
- CGRP is a vasoactive peptide that dilates blood vessels, is involved in pain signaling
What is the place of therapy of CGRP Receptor Antagonist?
Patients with insufficient response or Cl to treatment with triptans
What are the contraindications of CGRP receptor antagonists?
- Concomitant use of strong CYP3A4 inhibitors
- Pregnancy
- Use not recommended based on animal studies
What are the clinical pearls of CGRP Receptor Antagonists?
- Avoid repeat dosing of rimegepant within 24 hours
- Can repeat ubrogepant x 1 after 2 hours (max daily dose 200 mg)
- Expensive
What are the ADE of CGRP Receptor Antagonists?
- Nausea
- somnolence
- dry mouth
What is the MOA of Lasmiditan?
- Selective serotonin 5-HT1F receptor subtype agonist
- Lacks vasoconstrictor activity (i.e., lacks 5-HT1B/1D receptor activity )
What are the clinical pearls of Lasmiditan?
- Controlled substance: C-V
- Do not drive within 8 hours of administration
- Repeat dosing not indicated
- Expensive
What are the ADE of Lasmiditan?
High rate of adverse effects:
* Dizziness (most common), somnolence, paresthesia, fatigue, nausea
Low (<1%) cardiovascular side effects
What are some clinical pearls of Frovatriptan?
- Efficacy for menstrual migraine prevention
- Slowest onset, longest half-life; less frequent side effects
What are some clinical pearls of Rizatriptan?
- ODT, tablet
- Fastest oral onset
- Dose limited to 5mg for pts on propranolol
What are some clinical pearls of Naratriptan?
- Efficacy for menstrual migraine prevention
- Slow onset; less frequent side effects
What are the formulations of Sumatriptan?
- Tablet, nasal spray, injection SQ
What are some clinical pearls of Sumatriptan?
- Fast injectable onset, good for severe nausea
What are some clinical pearls of zolmitriptan?
- Tablet, ODT, nasal spray
- Efficacy for menstrual migraine prevention
What are some rescue outpatient treatment?
SC sumatriptan, DHE injection or intranasal spray, corticosteroids
What are some inpatient rescue treatment?
- Parenteral formulations of triptans
- DHE
- antiemetics
- NSAIDs
- anticonvulsants (valproate sodium and topiramate)
- corticosteroids or
- magnesium sulfate
What are the parenteral preferred antiemetics?
- Metoclopramide IV, prochlorperazine IM/IV, chlorpromazine IM/IV
- Administer with diphenhydramine IV (12.5-25 mg) to prevent akathisia and acute dystonic reactions
Who are considered candidates for migraine prophylaxis?
- Recurrent attacks producing significant disability
- Frequent attacks
- Increased risk for medication overuse headache
- Ineffective, contraindicated, or intolerant to acute treatment
- Uncommon migraine variants with risk for severe disruption or neurologic injury
- Patient preference
What is an adequate therapeutic trial of migraine prophylaxis?
- Trial of 2-3 months oral agents or 3-6 months for monoclonal antibodies needed to achieve clinical benefit
- Maximum effects seen by 6 months of treatment
- Continued for at least 6-12 months after frequency and severity have diminished
What are some FDA approved migraine prophylaxis treatment?
- Propranolol
- Timolol
- Divalproex
- Topiramate
- Botox
- CGRP monoclonal antibodies
What are some Level A established efficacy for migraine prophylaxis?
- Antiepileptics (Divalproex, Valproate, Topiramate)
- Beta Blockers (metoprolol, propranolol, timolol)
- ARB (candesartan)
What are some Level B migraine prophylaxis?
- Antidepressants (Amitriptyline, venlafaxine)
- Beta blockers (atenolol, nadolol)
- ACE (lisinopril)
What is the MOA of CGRP mAbs?
A monoclonal antibody that antagonizes CGRP receptor preventing vasodilation during migraine attacks
What is the MOA of Botulinum Toxin A?
Inhibits acetylcholine release at motor nerve terminals
What is the indication for Botulinum Toxin A?
- FDA-approved botulinum toxin for chronic migraines
- 2016 AAN guidelines = effective for chronic migraine
- HA ≥ 15 days/mo for ≥ months, with ≥ of 15 HA per month fulfilling criteria for migraine without aura
What are the ADR of botulinum toxin A?
neck pain, muscle weakness
Magnesium Oxide
Beneficial for patients with migraine with aura or menstrual migraines
Riboflavin (Vitamin B-2)
- “Probably effective” per guidelines
- ADR: Change in urine color (yellow/orange) otherwise tolerated
What is the MOA of Atogepant (Qulipta)?
CGRP receptor antagonist
What are the indications for Atogepant?
- Patients with < 15 headaches/month
- High disability from frequent migraines
- Failure to respond to other preventative therapies
What are some considerations of Atogepant?
- Avoid use with recent cardiovascular or cerebrovascular ischemic events
- ADR: Weight loss, constipation, nausea, fatigue, and drowsiness
What are some factors associated with poor outcome of tension headache?
- Coexisting migraine
- Sleep problems
- Anxiety/depression
- Poor stress management
What are the clinical presentations of tension headache?
- Mild-moderate intensity pain
- Dull, non-pulsatile tightness/pressure
- Bilateral pain (“hatband” pattern)
- Tender spots/localized nodules in some patient’s cervical or pericranial muscles
- Episodic or chronic frequency
Who are candidates of tension headache prevention?
- Consider in those with > 2 attacks/week, lasting > 3-4 hours, or disability
- Similar to migraine prevention approach with regards to comorbid conditions and side effect profiles
How do you prevent tension headache?
- TCAs most common
- SSRIs not effective without depression, SNRIs limited evidence
Cluster Headache
- The most severe of the primary headache disorders
- Excruciating, unilateral head pain occurring in series lasting for weeks or months
- Episodic or chronic
- Unknown etiology, inflammation of nerves resulting in injury to carotid artery
What is the epidemiology of cluster headaches?
- 4:1 female-to-male ratio
- > 65% tobacco smokers or history of smoking (cessation does NOT improve course)
- Genetic predisposition
What are the clinical presentations of cluster headache?
- A circadian rhythm of painful attacks
- Occur commonly and suddenly at night in spring/fall
- Excruciating, penetrating pain with a boring intensity in orbital, supraorbital, and temporal unilateral locations
- Nasal stuffiness, rhinorrhea, eyelid edema, facial sweating
What is the acute treatment of cluster headaches?
- Oxygen: Inhaled oxygen, 100% at 6-12 L/min for 15 minutes
- Triptans
- Sumatriptan 6 mg SQ (level A recommendation)
- Zolmitriptan 5-10 mg inhalation (level A recommendation)
- Ergotamine derivatives (no controlled trials to support use)
How do you prevent cluster headaches?
- Verapamil (1st lines): 360-960 mg/day (level C recommendation)
- Benefits seen within 2-3 weeks of therapy
- Lithium carbonate – 600-1200 mg/day (level C recommendation)
- Levels have not been established, but should be maintained 0.6-1.2 mEq/L
- Corticosteroids – prednisone 60-100 mg/day for 5 days then taper
- Suboccipital steroid injection level A recommendation
What are the risk factors of medication overuse headache?
- age (less than 50 years old)
- female
- smoking
- physical inactivity
- high daily caffeine intake (> 540 mg)
What are the clinical presentations of MOH?
- Occurs daily or nearly daily, usually present upon awakening
- Improves transiently with analgesics, returns as the medication wears off
- Patients often report morning headaches and neck pain due to overnight drug withdrawal or poor sleep
- Other symptoms: Nausea, anxiety, restlessness, difficulty concentrating, memory problems
- Headache on > 15 days/month AND pre-existing headache disorder
Which drugs can cause MOH?
- Triptan: 10 days/months for > 3 months
- Ergotamine: 10 days/month > 3 months
- Opioids: 10 days/month for > 3 months
- Aspirin: 15 days/month for > 3 months
- NSAIDs: 15 days/month for > 3 months
- Acetaminophen: 15 days/month for >3 months
How do you prevent MOH?
- ≤ 3 days per month of butalbital-containing analgesics (i.e., Fioricet®, Fiorinal®)
- ≤ 9 days per month of combination analgesics (caffeine)
- ≤ 15 days per month of NSAIDs
Menstrual-Related Migraine (MRM)
- The most common class of headaches that occur in women
- Related to a decline in estrogen during menstrual cycle, reducing serotonin production
- Family history
- More prevalent in individuals with a history of migraines and those on combined hormonal contraception
How do you treat Menstrual-Related Migraine?
Triptans:
* Level A: Frovatriptan 2.5 mg daily to BID
* Level B: Naratriptan 1 mg BID or Zolmitriptan 2.5 mg BID-TID
(May start 1-2 days before menses)
NSAIDs
* Naproxen - strongest evidence
* Aspirin - weakest evidence
(May start up to 1 week before menses and continued for no more than 10 days)
