Types of headaches
- Migraine
- Tension-type
- Cluster
- Daily persistent (new and chronic)
- Medication overuse
Red Flags for HA (8)
- sudden onset of headache, or severe persistent headache that reaches maximal intensity within a few seconds or minutes after the onset of pain (“thunderclap”, “worst headache of my life”)
- A worsening pattern
- Focal neurologic symptoms other than typical visual or sensory aura
- Fever associated with headache
- Any change in mental status, personality, or fluctuation in the LOC
- Rapid onset of headache with strenuous exercise, especially when minor trauma has occurred
- Nuchal rigidity or pain
- New headache
Migraine: Pathophysiology
what is believed to be the cause of auras?
Self-propagating wave of neuronal and glial depolarization across cerebral cortex
what are the migraine phases?
- Prodrome
- Aura
- Headache
- Postdrome (recovery)
when does the prodrome phase typically start?
what are some symptoms associated with prodrome phase?
o Usually starts 24-48 hours before pain
o Some symptoms: euphoria, depression, irritability, food cravings, constipation, neck stiffness, increased yawning
how do auras typically present
o Most are visual: bright spots, shapes, visual field loss
o Others: tingling numbness, language/dysphasia, motor
how is the headache phase in migraines? (type of pain, associated symptoms, etc.)
o Usually unilateral, throbbing/pulsatile
o Ranges in severity
o Can be accompanied by nausea/vomiting
o May also have photo-/phonophobia, osmophobia, cutaneous allodynia
o Usually lasts for ~4 hours to several days if untreated
describe the postdrome phase of migraines
o After headache resolves
o Patient may feel exhausted, elated, or euphoric
o Some report sudden head movements that cause pain at location of previous headache
what are some migraine triggers?
- Emotional stress (80 percent)
- Hormones in women (65 percent)
- Not eating (57 percent)
- Weather (53 percent)
- Sleep disturbances (fluctuations in sleep also) (50 percent)
- Odors (44 percent)
- Neck pain (38 percent)
- Lights (38 percent)
- Alcohol (38 percent)
- Smoke (36 percent)
- Sleeping late (32 percent)
- Heat (30 percent)
- Food (27 percent)
- Exercise (22 percent)
- Sexual activity (5 percent)
Abortive/Symptomatic Therapy
what are some mild analgesics used for abortive/symptomatic therapy?
- APAP, NSAIDs, ASA
- Combinations:
some OTC/Rx with ASA/APAP/Caffeine
Some Rx with APAP or ASA + butalbital +/- caffeine
Butalbital is a short- to intermediate-acting ________
barbiturate.
what are some effects of Barbiturates
depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, hypnosis, and dose-dependent respiratory depression.
there are some combo drugs with APAP or ASA + butalbital +/- caffeine
If the Rx is with ASA C-III controlled substance, what is the medication?
Fiorinal
there are some combo drugs with APAP or ASA + butalbital +/- caffeine
If the Rx is with APAP and is not controlled substance, what is it called?
Fioricet, Esgic-Plus, Dolgic
Triptans MOA
Serotonin 1b/1d agonists
o Inhibits release of vasoactive peptides
o Promotes vasoconstriction
o Blocks pain pathways in brainstem
o Inhibits transmission in trigeminal nucleus caudalis (blocks afferent input)
o May also activate 5-HT 1b/1d receptors in descending brainstem pathways to inhibit dural nociception
what is considered first-line for abortive therapy if mild analgesics fail?
triptans
choosing a triptan for a patient is usually based on what things?
Choice based on route of administration, cost, personal preference, PK differences
what are the names of triptan products (drug names)?
- Almotriptan (Axert): tablet only
- Eletriptan (Relpax): tablet only
- Frovatriptan (Frova): tablet only
- Naratriptan (Amerge): tablet only
- Sumatriptan + Naproxen (Treximet): tablet only
- Rizatriptan (Maxalt, Maxalt MLT): tablet and dispersible tablet
- Sumatriptan (Imitrex, Alsuma): tablet, nasal spray (solution and powder), subcutaneous injection, transdermal patch
- Zolmitriptan (Zomig, Zomig ZMT): tablet, nasal spray, dispersible tablet
- Some products/dosage forms still brand only
if you want to prescribe a triptan that is not in tablet form, what could you prescribe?
- Sumatriptan (Imitrex, Alsuma): tablet, nasal spray (solution and powder), subcutaneous injection, transdermal patch
- Zolmitriptan (Zomig, Zomig ZMT): tablet, nasal spray, dispersible tablet
triptans are best dosed when?
Best if used early in course of attack (within first few minutes)
if there is no relief after taking first triptan medication, when can you take another one?
Can repeat in 2 hours (except naratriptan 4 h)
what is the typical max dose for triptans?
All have max dose/24 period (usually 2 doses)
Triptans ADRs with PO administration?
paresthesias; asthenia and fatigue; flushing; feelings of pressure, tightness, or pain in the chest, neck, and jaw; drowsiness; dizziness; nausea; and sweating
Triptans ADRs with subcutaneous administration?
irritation at the site of injection (transient mild pain, stinging, or burning sensations)
Triptans ADRs with Intranasal administration?
bitter taste
Triptans: Limitations of Use
Rare but serious cardiac events, including coronary artery vasospasm, transient myocardial ischemia, atrial and ventricular arrhythmias, and myocardial infarction, predominantly in patients with risk factors for coronary artery disease.
why can these events occur?
triptans cause vasoconstriction!!!
contraindications for triptans (8)
- Hemiplegic or basilar migraine
- Known or suspected ischemic heart disease- Angina, MI, vasospasm, Prinzmetal’s angina, etc.
- Cerebrovascular syndromes- Stroke, TIA
- Peripheral vascular disease- Including ischemic bowel disease
- Uncontrolled HTN
- Use of another 5-HT1 agonist within 24 hours due to risk of serotonin syndrome–> Thought to be rare to nonexistent with SSRI/SNRI medications
- Use of ergotamine derivative within 24 hours
- Use of MAOI (usually within 2 weeks) (except eletriptan, frovatriptan, naratriptan)
it patient experiences significant nausea/vomiting with PO triptan medication, what should you do?
consider parenteral, nasal, or dispersible formulation
also Can pre-treat with antiemetic
triptan with Highest consistent success
Rizatriptan, eletriptan, and almotriptan
triptan that is -Most likely to produce short-term and sustained benefit
Eletriptan
triptans that are similar orally?
Sumatriptan, rizatriptan, eletriptan, almotriptan, zolmitriptan
triptans with Slower onset of action and lower efficacy?
Naratriptan and frovatriptan
if patients have a sulfa allergy which triptan should they avoid?
Almotriptan
when should you avoid use of Almotriptan
Avoid if renal/hepatic impairment + concomitant 3A4 inhibitor
possibly sulfa allergy
when should you avoid use of Eletriptan
Avoid use if within 72 hours of 3A4 inhibitors such as –azole antifungals, clarithromycin, ritonavir, nelfinavir
*High potential for DDI with 3A4 inhibitors
which triptan has the fastest onset of action
Rizatriptan
the taking rizatriptans, you Must adjust dose down if there is concomitant use of what drug?
propranolol
propranolol (increases rizatriptan levels by 70%)
what two Antiemetics are DA antagonist
o Metoclopramide (Reglan) given IV o Promethazine (Phenergan) or prochlorperazine (Compazine) given IV or IM
what two Antiemetics are 5-HT3 antagonist
o Ondansetron (Zofran) o Granisetron (Sancuso; Sustol)
these medications Can be monotherapy or adjunct for migraine pain as well as emesis
Antiemetics
DA Antagonist Antiemetics
Can be dosed with______ to prevent akathisia and acute dystonic reactions
IV diphenhydramine
DA Antagonist Antiemetics and diphenhydramine can cause what cardiac side effect?
QT prolongation
Ergots MOA
Bind to 5-HT 1b/1d receptors just as triptans do
when are Ergots used for HA?
Reserved for triptan failure
name of medication in Ergots class
Dihydroergotamine (DHE 45, Migranal)
medication name that can be used as Adjunct Therapy for headache?
Dexamethasone
ergots come in IV/IM/nasal formulations and might be used for ____ therapy
acute abortive
Dexamethasone has been Shown to be helpful in the acute setting to reduce _____.
headache recurrence
should Avoid overuse of Dexamethasone because it can lead to _______
glucocorticoid toxicity
when is Preventive Therapy for Migraines indicated?
o Frequent attacks o Long-lasting attacks o Significant disability o Uncommon migraine types/conditions Hemiplegic migraine Basilar type migraine Migraine with prolonged aura Migrainous infarction o Predictable onset: i.e., menstrual migraine
if Preventive Therapy for Migraines is unresponsive, what should you do?
May have to switch between drug classes if unresponsive
Preventive Therapy for Migraines Usually requires titration over ______ to see maximal effectiveness
weeks to months
there are Relatively few drugs with FDA indication for preventative migraine therapy, so many drugs used off-label for prophylaxis. what are some examples of these medications?
Propranolol, timolol, valproate, topiramate
drug classes for preventative migraine therapy (7 classes)
- Antihypertensives: BBs, CCBs, ACEIs/ARBs
- Antidepressants: TCAs
- Anticonvulsants
- Calcitonin gene-regulated peptide (CGRP) 5. antagonists
- Botulinum toxin
- Butterbur extract
limitations for antihypertensives used for preventative migraine therapy
caution in over 60, smokers, erectile dysfunction, PVD, Raynaud’s syndrome/disease, bradycardia/hypotension, asthma, DM, cardiac conduction disturbances, pregnancy
most common CCB used for preventative migraine therapy?
verapamil
common beta blockers used for preventative migraine therapy?
metoprolol, propranolol, timolol, nadolol, atenolol
which TCAs (antidepressants) are used for preventative migraine therapy?
amitriptyline, nortriptyline, doxepin
limitations for Antidepressants (TCAs) used for preventative migraine therapy
sedation, anticholinergic effects, weight gain, use in elderly
which Anticonvulsants are used for preventative migraine therapy?
o Valproate: avoid in child-bearing age women if possible
o Topiramate: caution in child-bearing age women
o Gabapentin
which anticonvulsant should you use for preventative migraine therapy if you have a female patient that is child bearing age.
Gabapentin
what is the name of the drug that is a Calcitonin gene-regulated peptide (CGRP) antagonists used as preventative migraine therapy treatment
Erenumab (Aimovig)
CGRP mediates________ pain transmission and vasodilatory component of neurogenic inflammation
trigeminovascular
how is Erenumab (Aimovig) dosed?
Monthly subcutaneous administration
Botulinum toxin only has evidence for chronic migraine (>15 days per month for at least 3 months) NOT _______ migraines
episodic migraines
why is Butterbur extract not usually recommended as preventative migraine therapy
not usually recommended due to lack of long-term safety and regulation
Contains alkaloids that can be hepatotoxic and potentially carcinogenic
what medications are good first-choice options for treating tension headaches?
Simple analgesics are first-choice
o APAP (good in pregnancy), ASA, NSAIDs o ****Rx v. OTC o IBU (200-400 mg), naproxen (220-550 mg) or ASA (650-1000 mg)
when treating tension headaches, analgesics with a combo of ________ might help but can increase ADRs
caffeine
in treating tension headaches, you should AVOID combinations of analgesics with ______.
butalbital or opioids or muscle relaxants
in treating tension headaches, IM _______ is good option if presenting to facility
ketorolac
what are some Nonpharmacologic therapy first-line options for treating tension headaches
relaxation, cognitive-behavioral therapy, biofeedback, acupuncture, PT, etc.
which drug class has the most evidence for being used as preventative therapy for tension headaches
TCAs
describe cluster headaches
Short-lasting, very severe pain, usually unilateral
Typically accompanied by autonomic symptoms- Ipsilateral tearing and/or rhinorrhea
Often occur many times per day over several days
first line therapy for cluster headaches
Oxygen: 100% via non-rebreather at 12-15 L/min
patients with what comorbidity may need to avoid first line therapy for cluster headaches
first line therapy is oxygen, so Only limitation is with COPD patients where O2 might lead to hypercapnia
when treating cluster headaches, _________ can be sued if response is not complete with O2 or if not available
Subcutaneous sumatriptan
what are some alternatives that can be used for Subcutaneous sumatriptan when treating cluster headaches?
IN sumatriptan, IN zolmitriptan, oral zolmitriptan
ergotamine formulations are also available for second-line options very early in the attack
drug of choice for preventative therapy in cluster headaches
verapamil
second line options for preventative therapy in cluster headaches
glucocorticoids, lithium, valproate, topiramate, gabapentin
what is medication overuse headache caused by?
Caused by use of medications too frequently which results in “rebound” headaches
Pathophysiology of medication overuse headache is uncertain but believed to be due to?
o Genetic predisposition
o Central sensitization like in migraines
o Biobehavioral factors
which medications can cause medication overuse headache
All acute symptomatic medications used to treat HA have potential to cause MOH
medications with the highest risk to cause medication overuse headache
o Butalbital-containing combination analgesics
o APAP
o Opioids
o ASA
medications with the Intermediate to high risk that can cause medication overuse headache
Triptans/ergotamine derivatives
medications with the lowest risk to cause medication overuse headache
NSAIDs
medication overuse headache diagnosis criteria
o HA > 15 days per month
o Regular overuse of more than three months with acute/symptomatic drugs-
1. Ergotamine, triptans, opioids, or combination analgesics > 10 days per month for more than three months
2. Simple analgesics >15 days per month for more than three months
medication overuse headache treatment
- Patient education as to cause and how to prevent
- Withdraw offending drug therapy
- Start preventive medication according to HA type
when treating medication overuse headache, how long may it take for the HA to resolve?
May take weeks for headaches to resolve
when treating medication overuse headache, Withdrawal of offending medication may occur as outpatient or may require admission for inpatient withdrawal. when would admission for withdrawal be indicated?
patients taking barbiturates, opioids, or tranquilizers
options for Bridge therapy when treating medication overuse headache
o Long-acting NSAID, prednisone: good for triptan/APAP overuse
o Clonidine helps with opioid overuse
how should you approach treatment for Chronic Daily Headaches (CDH)
Identify the phenotype and treat accordingly