Headaches Part 2

Migraine is the 3rd most prevalent disease in this world
• One of the most common complaints encountered by
healthcare practitioners and among the top 5 reasons given by
adults 18 to 44 years of age for visiting US emergency
departments.
• 20.7% women and 9.7% men in the US have 1+ migraine
headaches per year.
• 1 or more TTH occurs in 38% to 86% of men and women per
year
• For cluster headaches, the ratio if 4:1 (Male: Female), 65% of
patients have a history of smoking.

• Primary Headaches
• Migraine
• Tension-type
• Cluster

• Secondary Headaches
• Tumor
• Trauma
• Infection
• Withdrawal

- • Associated Symptoms
• Frequency
• Duration
• Onset

Triggers
• Predictable?
• Better/worse?
• Sleep?

Rule Out Secondary Causes
• Imaging: CT, MRI, MRA, MRV
• Lumbar Puncture

mnemonic for identifying secondary headaches.

- Systemic: fever, weight loss, fatigue (infection, metastatic cancer, HIV, immunosuppression)
• Neurologic: altered consciousness, focal deficits (encephalitis, stroke)
• Neoplasm history
• Onset: sudden, thunderclap (hemorrhage)
• Older Age (>50): new, progressive (temporal arteritis)
• Pattern Change, Position, Papilledema: (tumor, intracranial pressure), Precipitated by sneezing, coughing, or exercise, Progressive, Pregnancy, Painful eye with autonomic features, Post-trauma, Pathology of the immune system, Painkiller overuse

LIFE THREATENING!!!

Adverse Effect
• Nitrates (nitroglycerin),
• BP medications: calcium channel blockers, ACE inhibitors, alpha- and beta-
adrenergic agnoists/blockers
• Medications for erectile dysfunction: Sildenafil (Viagra), vardenafil (Levitra,
Staxyn), tadalafil (Cialis) and avanafil (Stendra)
• Estrogen

• If Abruptly Withdrawn
• Caffeine, opioids, amphetamines, estrogen

• Due to Overuse
• General analgesics (butalbital, NSAIDs, aspirin)
• Anti-migraine (triptan, ergots)

1. Premonitory Symptoms (77%)
▪ Onset: Hours to days before headache onset

Symptoms Include:
• Neurologic: Allodynia, photophobia, phonophobia, hyperosmia, difficulty concentrating
• Psychological: Anxiety, depression, fatigue, irritability, drowsiness
• Autonomic: Polyuria, diarrhea, constipation
• Constitutional: Food cravings, decreased food intake, stiffened neck, increased thirst

2. Aura (25%)
▪ Onset: Up to 60 minutes before headache
• Gradual development over 5 minutes
▪ Symptoms Include:
• Visual: Disturbances (i.e., flashes/shimmers of light, partial vision loss)
• Sensory/Motor: Paraesthesias of face and arms (i.e., aphasia, weakness, hemiparesis)

3. Headache
▪ Onset: Gradual, with peak intensity over minutes to hours
• Last 4 to 72 hours
▪ Symptoms Include:
• Gastrointestinal: Nausea, vomiting
• Sensory: Photophobia, phonophobia, osmophobia
• Psychological: Impaired concentration, fatigue, dizziness, irritability

4. Postdrome/Resolution
▪ Symptoms Include:
• Psychological: Exhaustion, irritability, impaired concentration, euphoric

• Episodic Migraine
• <15 headache days/month

• Chronic Migraine
• ≥ 15 headache days/month for > 3 months, with ≥ 8 headaches that have features of migraine headaches

• Status Migrainosus
• Migraine > 72 hr

• Female gender
• Age 25-50
• Low education status
• Depression
• Obesity
• Stress
• Caffeine overuse

Acute
• Ice to head
• Rest in dark, quiet environment

Prevention
• Trigger avoidance
• Behavioral: CBT, biofeedback

Headache Diary
• Frequency, severity, duration
• Identify triggers

Lifestyle
• Regular sleep, exercise
• Avoid smoking, caffeine
• Aerobic exercise, biofeedback, other forms of relaxation training

Neuromodulation Devices
• eTNS: external trigeminal nerve stimulator
• REN: remote electrical neuromodulation
• nVNS: noninvasive vagus nerve stimulator

Abortive Treatment = acute, symptomatic treatment

General Analgesics
• NSAIDS, ASA, APAP

Migraine-Specific
• Triptans: 5-HT1B,1D receptor agonists
• Dihydroergotamine: 5-HT1 receptor agonist
• Lasmiditan: 5HT1F agonist
• Gepants: small-molecule CGRP antagonists

Other Options
• Anti-emetics
• Corticosteroids
• Muscle relaxants for select patients

• Headache severity
• Time: Onset and Duration of headache (route of administration)
• Effectiveness
• Patient preference
• Contraindications/adverse effect profile

Indication: Infrequent/mild-moderate acute migraine episodes

Agents:
• Efficacy enhance when combined with caffeine

• Combination agents
• Excedrin® Acetaminophen (APAP) + aspirin (ASA) + caffeine 250mg/250mg/65mg- for 18
yrs or older Max 2 per day
• Fioricet® APAP + butalbital + caffeine (avoid)

• Acetaminophen
• Aspirin – irreversible inhibitor of the enzyme cyclooxygenase (COX1 and 2)

• NSAIDS:
• Reversible inhibition of the enzyme cyclooxygenase (COX1 and 2)
• OTC: ibuprofen, naproxen

Indication: acute migraine episode (off-label use)
MOA: Aspirin irreversible inhibits the cyclooxygenase (COX) pathways
Acetaminophen not clear (weak inhibit COX, inhibit serotonergic pathways)
Efficacy: Acetaminophen (paracetamol-international name) or Aspirin as a monotherapy usually not effective enough

Combinations:
• Caffeine- improves analgesic effect, may work faster
• Butalbital- a sedative, avoid as increased risk of chronic migraine, overuse HA
• Oxycodone - Percodan (ASA) & Percocet (APAP); avoid as increased risk of chronic migraine, overuse HA

Indication: acute migraine episode. MOA- Reversible inhibition of COX

• Limit use to minimize risk of medication overuse headache (< 10 days/mo
for migraine specific meds, < 15 days/mo for acetaminophen/aspirin/NSAIDS)
• Cardiovascular ADRS: Can increase the risk of a heart attack, stroke and high blood pressure
• Can increase risk for bleeding (i.e. Gastroduodenal ulcer)

Mechanism: 5-HT1B,1D Receptor Agonists (inhibit the release of vasoactive and pro-
inflammatory neuropeptides including calcitonin-gene-related peptide (CGRP));
vasoconstriction of intracranial arteries. Inhibit nociceptive neurotransmission and plasma
protein extravasation by activating 5-HT1B,1D receptors in the descending brainstem pain-
modulating pathways; block neurogenic inflammation

Indication: 1st Line for moderate-severe acute migraine episodes
▪ Specific CNS activity compared to general analgesics

Use: 1 dose PRN for migraine; may repeat in 2 hr
▪ Key efficacy measure: 100% symptom and pain reduction in < 2 hours

Limit: 2 doses/day, 2 days/week
▪ Note: Triptan use for > 10 days/month can lead to rebound or daily headache

ADRs: Paresthesia, dizziness, flushing, warmth, “triptan sensations”
(tightness; pressure in chest/throat), GI distress

Warnings: Evaluate cardiovascular risk factors prior to initiation because triptans can cause vasoconstriction. Watch for medication overuse. Monitor patients with seizure history

Contraindications:
• Cardiovascular: history of ischemic or vasospastic heart disease, MI, angina or accessory pathway arrhythmia;
• Cerebrovascular: history of stroke, TIA, or hemiplegic/basilar migraine
• Other: peripheral vascular disease, uncontrolled HTN, ischemic bowel disease, smoking, hepatic or renal dysfunction
• Triptans should not be used within 24 hours of the use of an ergotamine preparation or a different triptan

• Faster Onset (0.25-2hrs) but shorter duration (half-life <4 hr except eletriptan =4hr)
• Sumatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan

• Slower Onset (>1-2hr) but less headache recurrence
• Naratriptan(onset 1-3 hr; half-life 6 hrs); frovatriptan (onset 2-3 hr; half-life 26 hrs)

In comparison to sumatriptan 100mg:
• Lower adverse events: naratriptan(2.5mg), almotriptan(12.5 mg), frovatriptan(2.5mg)
• Better 2-hr pain response: eletriptan(80mg), rizatriptan(10mg), almotriptan(12.5mg)
• Lower recurrence rate: frovatriptan(2.5mg), eletriptan(40mg) (slightly long half-life)

Indication: Patients with nausea and/or vomiting

Onset: SQ (10 min) < IN (15-30 min) < SL (30 min)
• Subcutaneous injection (SQ): Sumatriptan
• Intranasal inhalation (IN): Sumatriptan, zolmitriptan
• Sublingual (SL): Rizatriptan, zolmitriptan

SSRI/SNRI
• Risk of Serotonin Syndrome (low)

Ergot derivative/other triptan within 24 hours
• Contraindicated
• Affected Medications: all in class

MAOI administration within 2 weeks
• Contraindicated
• Affected Medications: Sumatriptan, Rizatriptan, Zolmitriptan

CYP3A4 inhibitors
• Screen medication list
• Affected Medications: Almotriptan, Eletriptan

Propranolol
• Increases concentration of rizatriptan, zolmitriptan, frovatriptan, eletriptan

Mechanism: 5-HT1B,1D receptor agonist + long acting NSAID

Use: 1 dose (85mg/500mg) PRN for migraine; may repeat in 2 hours
• Combination tablet approved for episodic migraine only

Efficacy of Combination:
• Sumatriptan/naproxen was superior in achieving 24-hour pain relief endpoint compared to monotherapy with either agent
• Decreased incidence headache recurrence in 24 hours

ADRS: No difference in ADR occurrence with combo

Indication: moderate-severe acute migraine episodes
MOA: non-selective 5-HT receptor agonist
Agents:
Ergotamine tartrate (SL, Ergot/Caffeine suppository combo) Not recommended: more
ADRs, less effective
Dihydroergotamine (DHE) (Intranasal, IV, Subcutaneous, IM injection)
• Preferred over ergotamine: Proven effective, less ADRs, faster IN/IM route
• Place in Therapy: Patients who experienced rebound headache with triptans;
patients who experienced medication overuse headaches
• Intravenous DHE for chronic intractable migraine headache or status migrainosus
• Combine with an antiemetic if administer intravenously and consider adding with
other routes as well

ADRs: N/V, vasospasm, ischemia, fibrotic valves, stroke, hemorrhage, ergotism
(gangrene of extremities), abdominal pain

Contraindications
• Renal/hepatic failure, cardiac (ischemia, MI, angina), hemiplegic/basilar
migraine, peripheral vascular disease (Raynaud’s), uncontrolled hypertension,
pregnancy, breastfeeding

DDIs
• Potent CYP3A4 inhibitors (i.e protease inhibitors, azole antifungals, and some
macrolide antibiotics).
• Vasoconstrictors (peripheral or central)
• Serotonin modulators (separate 24-hr from triptan)

▪ MOA: 5HT1F agonist
▪ Advantage: lacks vasoconstrictor activity
▪ Current role- when cardiovascular risk factors caution use of triptans or failed 2 triptans
▪ Dose: 50 mg, 100 mg, or 200 mg orally, as needed
• No more than one dose should be taken in 24 hours
• If the 50 mg dose does not work take 100mg in a subsequent attack
▪ CNS depression: Wait 8 hours after dosing before driving or operating machinery
▪ May be taken with or without food
▪ Controlled substance (C-V) Some potential for abuse due to euphoria
▪ The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established
• Risk of rebound may be greater if used 10 or more days per month

Agents:
▪ Ubrogepant (Ubrelvy®) – Dec 2019 for acute treatment of migraine
▪ Rimegepant (Nurtec®) – Feb 2020 for acute; off-label for prevention
▪ Investigational: Zavegepant (IN formulation) and Atogepant (prevention)
• Avoid use in severe renal impairment (Ubrogepant) and hepatic impairment (Rimegepant)

• Consider for patients who have failed two triptans or cannot use triptans. May have less
risk of medication overuse headache

Safety & Efficacy- need more long-term post marketing studies and comparison studies with
triptans.. Prevents 1-2 episodic migraine/mo vs placebo. 25% of patients have at least 50%
decrease in migraine days/mo

Acute:
• Start with 50 to 100 mg as a single oral dose (time to peak ~ 1.5 hrs)
• May repeat once based on response and tolerability after ≥2 hours. Maximum dose: 200 mg per 24 hours
• Half-life ~5 to 7 hours.
• The safety of treating >8 migraines/month has not been established.

Pharmacokinetic Considerations: Metabolized by CYP3A4 also
BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor)
Do not use with strong CYP3A4 inhibitors

ADRs: Drowsiness, nausea, dry mouth

Cost: ~\$100 per tablet

• Acute treatment: 75 mg orally - disintegrating tablet as a single dose; maximum:
75 mg/24 hours. Onset < 2 hours Effect should last ~ 48 hours
• Migraine prevention (off-label use): Oral: 75 mg every other day. May take 4
weeks to have full effect.

• Metabolism/Transport Effects Substrate of CYP3A4 (major), BCRP/ABCG2, CYP2C9 (minor), P-glycoprotein/ABCB1 (minor)
• Avoid with strong CYP3A4 inhibitors/inducers

• ADRS: Nausea (2%) <1% for skin rash, hypersensitivity reaction, dyspnea

• Cost: 1 tablet > \$100

Mechanism: Dopamine Receptor Antagonist

Indication: Monotherapy or adjunctive to abortive treatment in patients with refractory headaches
▪ Severe nausea/vomiting
▪ Efficacy for migraines
• Increased response and absorption of analgesics

Agents: IV/PO metoclopramide, prochlorperazine, chlorpromazine, droperidol

Most commonly used as a rescue agent for status migrainosus

Dexamethasone 10 to 25mg IV or IM x1 in combination with patient’s standard abortive therapy

• Reduction in migraine occurrence for up to 72 hours (NNT: 9)
• No additional benefit for immediate headache relief

Prednisone: Addition of oral prednisone did not prove to be beneficial in prevention of recurrent headaches

EARLIER IS BETTER!
Efficacy: Pain or symptom-free at 2 hours post-dose
• Without recurrence
• 20-80% response to an NSAID or triptan, depending on agent

Individualized Response
• e.g. if fail 1 triptan, can try another

Combination Therapy
• Inadequate response to monotherapy
• Any 2 agents from different classes (e.g. NSAID + triptan)

Moderate to severe migraine, particularly if the migraine is accompanied by
vomiting or significant nausea
• sumatriptan 6 mg SQ, or
• parenteral antiemetic agent (metoclopramide 10 mg or prochlorperazine (10
mg) with of diphenhydramine (12.5 to 25 mg IV every hour up to two doses) to prevent akathisia and other dystonic reactions, or
• dihydroergotamine (DHE 45) 1 mg IV combined with IV metoclopramide 10 in patients without ischemic vascular disease involving cardiac, cerebrovascular, or peripheral circulations.

Consider adjunctive treatment with IV or intramuscular dexamethasone (10 to 24
mg) to reduce the risk of early headache recurrence

Therapeutic lifestyle measures:
• good sleep hygiene, routine meal schedules, regular exercise, and management of migraine
triggers are appropriate for all patients with migraine.

Herbs/supplements: no longer recommended or need more study
• 2012 AAN Guidelines in 2012 from the AAN concluded that Petasites (butterbur) feverfew,
magnesium and riboflavin are probably effective.

Nonpharmacologic: may be beneficial
Neuromodulation: use electric current or a magnetic field to centrally or peripherally stimulate
the nervous system to minimize pain
3 devices (eTNS, nVNS, and sTMS) acleared for monotherapy or adjunctive therapy for
preventive migraine treatment
3 devices (nVNS, REN, and sTMS) are cleared for the acute and preventive treatment of migraine
in adolescents between 12-17 years of age

Indications:
• Frequent or long-lasting migraine headaches
• Migraine attacks that cause significant disability or diminished quality of life
despite appropriate acute treatment
• If needing acute therapy more than twice per week
• Contraindication to acute therapies
• Failure of acute therapies
• Serious adverse effects of acute therapies
• Risk of medication overuse headache
• Menstrual migraine

• Patient Preference
• Contraindications/adverse effects
• Take ADVANTAGE of side effect profile (i.e. topiramate for obesity)

• Comorbidities
• Depression, seizures, hypertension
• Note: doses for migraine prophylaxis may be suboptimal for other indications

• Combining agents from different classes may improve efficacy

• Goals of Treatment:
• Reduce frequency, duration, and severity of migraine attacks/headache days
• Reduce by 50% within 3 months of starting preventative treatment
• Improve response to acute treatments
• Reduce overuse of abortive medications

• Antidepressants
• Anticonvulsants
• Beta blockers
• Botulinum Toxin (Botox®)
• CGRP Antagonists

Agents: Amitriptyline, venlafaxine

Considerations for therapy/ADRs:

Amitriptyline: 1st or 2nd line
Increased number of trials showed its efficacy (compared to venlafaxine)
Nortriptyline may be used if need less ADR but lack of controlled trial
ADRs: Dizziness; dry mouth; sedation (give at bedtime; if too sedating, can use
nortriptyline); weight gain; orthostatic hypotension; QT prolongation; lower seizure
threshold

Venlafaxine extended-release: 2nd line
May be beneficial in patients with co-morbid depression and anxiety disorders
ADRs: Hypertension; insomnia; worsened anxiety
Avoid with MAOI use within 12 days. Caution in patients with seizures

Agents: Topiramate, valproate
• Topiramate is FDA-indicated for migraine prevention
• Proven efficacy for chronic migraine prevention

Considerations for Therapy/ADRs:
• Topiramate:
• Known teratogen (causes cleft palate)
• ADRs: Weight loss; kidney stones; cognitive delay (difficulty finding words, concentrating); drowsiness; paresthesia
• Dose adjustment for renally impaired patients

• Valproate:
• Known teratogen (causes spina bifida; decreased IQ)
• ADRs: Headache; nausea; weight gain, hepatotoxicity;
thrombocytopenia; alopecia

• Agents: metoprolol, propranolol, timolol, candesartan, lisinopril
• Metoprolol and propranolol are FDA-indicated for migraine prevention
• Metoprolol, propranolol, and timolol are 1st-line (reduce at least a 50% reduction in migraine
frequency (atenolol and nadolol may be effective)
• Candesartan and lisinopril are 2nd-3rd line (reduce migraine days around 25%)
• Nicardipine and verapamil are 3rd line (poor evidence for verapamil)

• Considerations for Therapy/ADRs:
• Caution in patients with comorbidities (i.e., asthma, diabetes, thyroid disease)
• ADRs: Bradycardia, hypotension, depression, weight gain, dizziness (decreased exercise
tolerance)
• Beta-Blockers good in patients with comorbid HTN or angina
• If taking rizatriptan limit dose to 5 mg/dose if taking propranolol
• The dose of rizatriptan must be adjusted downward in patients who take propranolol, since propranolol increases rizatriptan levels by 70%

• Can cut 2 more headaches/mo compared to placebo ( Prevents, on average, 8 to 9
headache days and migraine/probable migraine days a month (vs 6 to 7 for placebo)
• Indicated for patient with 15 or more headaches days per month, with headaches lasting
4 or more hours per day in patients 18 and older. (It is not approved for 14 or fewer headache days a month.)
• Administered every 3 months.
• BOTOX® may cause serious side effects:
• Problems swallowing, speaking, or breathing, due to weakening of associated
muscles
• Loss of strength and all-over muscle weakness, double vision, blurred vision and
drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly,
loss of bladder control, trouble breathing, and trouble swallowing
• Do not drive a car, operate machinery until familiar with the effects

Large molecules in the form of monoclonal antibodies directed against the CGRP receptor or ligand

Agents:
• Erenumab (Aimovig®) monthly SubQ self-injection
• Fremanezumab (Ajovy®) monthly SubQ self-injection, (quarterly option)
• Galcanezumab (Emgality®) monthly SubQ self-injection
• Eptinezumab (Vyepti®) 30 min IV infusion in clinic

ADR: Injection site reactions; CGRP causes vasodilation and could have cardiovascular effects
(studies excluded pts with CV risk factors). Erenumab reports of HTN and constipation

Use: Due to cost, Consider for patients with adherence issues, side effects, poor response, or
drug interaction concerns with oral agents. Can be combined with oral agents. Special
authorizations needed. (after 8-week trial of 2 or more other agents)

• Third-line agent
• 2 mg BID may be as effective as propranolol 40 mg BID
• Antihistamine that impacts serotonin, comes in a syrup, and may help kids sleep
• ADRs: Weight gain and sedation
• Considerations: Use caution in patients taking MAOIs or CNS depressants, patients involved in activities requiring alertness and coordination, patients in whom anticholinergic effects are
undesirable
• Considered safe in pregnancy

Migraine headaches may improve independent of treatment. If the headaches are well
controlled, slowly taper the drug if possible. Many patients experience continued relief
with either a lower dose or cessation of the medication.
• Efficacy ("success") demonstrated for patients that:
• Use medication for at least 2 months at target or maximally tolerated dose
• Decrease in migraine attack frequency or number of headache days per month is reduced by 50% or more

• After 6 to 12 months of successful prophylactic therapy:
• Consider tapering and discontinuing the prophylactic medication
• If headache frequency increases as dose is reduced, increase dose and use slower taper

Agents: Triptan or long-acting NSAID (naproxen)

Given daily for 3 days prior to and throughout menstrual cycle

Evidence (all off-label):
• “A” [Effective]: Frovatriptan
• “B” [Probably effective]: Naratriptan, zolmitriptan
• Other triptans studied: Rizatriptan, almotriptan
• Rizatriptan was only agent to demonstrate two-hour pain relief and 24-hour sustained pain relief

≥ 15 headache days/month
Overuse of acute headache medications for > 3 months
APAP, NSAIDs: > 15 days/month
Triptan, ergot, combination medication: > 10 days/month
Most offending agents: butalbital and Narcotics

Diagnose in addition to chronic tension or migraine

Management:
Abortive Therapy Plan:
• Discontinue offending agent
• Switch to another abortive agent in a different class
• Taper over 2-4 weeks
• Cross-titrate with another abortive agent in a different class
• Newly initiated abortive agent should be used no more than 2
days per week
Preventative Therapy Plan: Initiate medication (controversial, limited data that prevention therapy will have an impact as takes several weeks to work)

Most common headache type. Yearly prevalence rates for episodic TTH are ~80
percent

Unlike migraine: Generally, No nausea/vomiting, photophobia or phonophobia
≥ 2 of the following symptoms:
▪ Location: Bilateral
▪ Type of Pain: pressing or tightness; non pulsating
▪ Intensity: mild to moderate
NOT aggravated by physical activity (walking up stairs & similar routines)

Despite its frequency, few placebo-controlled preventive therapeutic trials have been conducted in TTH

Infrequent episodic: < 1 headache/month
Frequent episodic: 1-14 headaches/month, for at least 3 months or more
Chronic: ≥ 15 headaches/month, for at least 3 months or more

Non-Pharmacologic: CBT, acupuncture, heat/ice, massage, rest, and biofeedback
▪ Many patients have comorbid sleep problems, anxiety, stress, or depression
▪ Check for teeth clinching at night (mouth night guard)

Acute Treatment: OTC analgesics
▪ NSAIDS, aspirin, acetaminophen (less effective but preferred if pregnant)
▪ If poor response to monotherapy add (i.e two tablets of combined acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg)
▪ On average, limit medication to ten days per month and 2 doses per day- to minimize overuse headache risk

Tricyclic antidepressants:
• Amitriptyline)- [1st Line]: 10-12.5 mg nightly, then increase by 10-12.5 mg every 2-3 weeks to max 100-125mg/d
• Increased risk of cardiac conduction abnormality and arrhythmia
• Weight gain and sedation
• Nortriptyline- less sedating (mild to moderate). Weight gain
• Protriptyline- nonsedating, the mild stimulating effect can worsen anxiety and
panic disorders. Weight loss.

• Less evidence: mirtazapine, venlafaxine, tizanidine, gabapentin, topiramate
• SSRIs: not effective
• Behavioral therapies: CBT, relaxation, biofeedback, regulate
sleep/exercise/meals

• At least 5 attacks fulfilling the criteria:
• Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15-180 minutes (without treatment)
• Either one or both of the following:
1. a sense of restlessness or agitation
2. At least one symptom, ipsilateral to side of headache: Forehead and facial sweating,
flushing, sensation of fullness in the ear, lacrimation, nasal congestion and/or rhinorrhea,
OR eyelid edema
• Attacks happen anywhere from eight per day to every other day for more
than half of the time when active
• Half the patients may also have associated symptoms similar to
migraine(photophobia, phonophobia)

• Episodic: occurring in periods lasting from 7 days to 1 year, separated by pain-free periods lasting at least 3 months. Generally, 6-12 weeks with attacks more common in spring and autumn.
• Chronic: Occurring without a remission period, or with remission lasting <3 months, for at least a year
• Triggers: alcohol, foods with nitrates, Nitroglycerine, strong odors,

• Acute:
• 100% oxygen: 6-10 liters per minute administered by face mask
• Sumatriptan SQ/IN, Zolmitriptan IN at pain onset

• Prevention: (in order of preference). Treat for up to 4 weeks after an attacks have settled, then gradually taper:
1. Verapamil for episodic or chronic cluster headache - 1st line
2. Topiramate, melatonin
3. Lithium carbonate for episodic and chronic cluster headache attacks check cp 12
hr after dose, every 1-2 mo. (0.4-1.2 mEq (mmol)/L ) Requires regular monitoring
• Used as resort option when alternatives fail or are contraindicated
4. Galcanezumab (Emgality)-approved for episodic cluster, \$\$, no long-term data