Headache:

A Practical Summary for Primary Care Providers

ANNETTE GOODMAN, DO
REDINGTON NEUROLOGY
Objectives

 Be able to identify common types of primary headache syndromes seen in

primary care:
 Medication overuse headache
 Migraine
 Cluster Headache
 Muscle Tension Headache
 Avoid triggers contributing to medication overuse headache
 Differentiate between treatment options for migraines, both acutely and as a
preventative
 Be aware of emerging therapies for migraines
Prevalence

 ½ - ¾ of adults have suffered from a headache within the past year.

 30% have had a migraine in the past year.
 1.7-4% have had a headache at least 15 days or more each month.
 Severe headache / migraine reported in 1out of 6 Americans over a 3 month period.
 9.7% males, 20.7% females
 Fifth leading cause of ER visits
 Third leading cause among females age 18-44
 1.3% of outpatient visits
 Third highest cause nationwide of years lost to disability [YLD].

Headache. 2018 Apr;58(4):496-505. doi: 10.1111/head.13281. Epub 2018 Mar 12.

World Health Organization fact sheet, 2016

Today’s Scope:

 Medication Overuse Headache

 Migraine
 Tension-type Headache
 Cluster Headache
Introduction

 NO pain receptors in the parenchyma [the brain tissue itself]

 Pain receptors ARE present in:
 Blood vessels
 Meninges
 Scalp
 Skull
Medication Overuse Headache
Medication Overuse Headache

 Also known as Rebound Headache

 Defined as:
 Headache present on >15 days/month.
 Regular overuse for >3 months of one or more drugs that can be taken for acute and/or
symptomatic treatment of headache.
 Headache has developed or markedly worsened during medication overuse.

Ther Adv Drug Saf. 2014 Apr; 5(2): 87–99.

Medication Overuse Headache

 Can be precipitated by many agents:

 NSAIDs
 Acetaminophen
 Aspirin
 Caffeine
 Triptans
 Opioids
 Butalbital
 Ergotamines
Pathophysiology

 Etiology is uncertain given multiple medication triggers

 Present in patients predisposed to headache
 Consideration given to chronic low serotonin, elevated CGRP and central
sensitization

Ther Adv Drug Saf. 2014 Apr; 5(2): 87–99.

Medication Overuse Headache

 Goal: withdrawal of offending agent

 Baseline headache pattern can therefore be established
 Achieved by one of three methods:
 Abrupt withdrawal
 Gradual wean
 Steroid taper – data does not prove superiority
 After successful wean, relapse is 20-40%
 Limit future abortive use to no more than twice weekly in susceptible patients
Migraine
Introduction

 Prevalence:
 Women 25% (lifetime)
 Men 8% (lifetime)
 28 million persons have migraine each year in the U.S.
 Highest from 25-50 years of age

 Genetics
 About 70% of migraineurs have a positive family history in a first-
degree relative
 Unknown mode of transmission
Strange (Scary) Facts

 Increased prevalence of:

 MVP
 PFO
 HTN
 Stroke
 Epilepsy
 Atopic allergies
 Asthma
 IBS
 Depression
 Bipolar disease
 Anxiety disorders
 Panic attacks
Migraine
The International Classification of Headache Disorders, 3rd edition

 A. At least five attacks fulfilling criteria B–D

 B. Headache attacks lasting 4–72 hours (when untreated or unsuccessfully treated)
 C. Headache has at least two of the following four characteristics:
 1. unilateral location
 2. pulsating quality
 3. moderate or severe pain intensity
 4. aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing
stairs)
 D. During headache at least one of the following:
 1. nausea and/or vomiting
 2. photophobia and phonophobia
 E. Not better accounted for by another ICHD-3 diagnosis.
Cephalalgia 2018, Vol. 38(1) 1–211
Migraine

 Migraine without aura [common migraine]

 Migraine with aura [classic migraine]
Migraine
 1. Migraine
 1.4 Complications of migraine
 1.1 Migraine without aura
 1.4.1 Status migrainosus
 1.2 Migraine with aura  1.4.2 Persistent aura without infarction
 1.2.1 Migraine with typical aura
 1.4.3 Migrainous infarction
 1.2.1.1 Typical aura with headache
 1.4.4 Migraine aura-triggered seizure
 1.2.1.2 Typical aura without headache
 1.5 Probable migraine
 1.2.2 Migraine with brainstem aura
 1.5.1 Probable migraine without aura
 1.2.3 Hemiplegic migraine
 1.5.2 Probable migraine with aura
 1.2.3.1 Familial hemiplegic migraine (FHM)
 1.2.3.1.1 Familial hemiplegic migraine type 1 (FHM1)
 1.6 Episodic syndromes that may be associated with
migraine
 1.2.3.1.2 Familial hemiplegic migraine type 2 (FHM2)
 1.6.1 Recurrent gastrointestinal disturbance
 1.2.3.1.3 Familial hemiplegic migraine type 3 (FHM3)
 1.6.1.1 Cyclical vomiting syndrome
 1.2.3.1.4 Familial hemiplegic migraine, other loci
 1.6.1.2 Abdominal migraine
 1.2.3.2 Sporadic hemiplegic migraine (SHM)
 1.6.2 Benign paroxysmal vertigo
 1.2.4 Retinal migraine
 1.6.3 Benign paroxysmal torticollis
 1.3 Chronic migraine

Cephalalgia 2018, Vol. 38(1) 1–211

Pathophysiology

 The neurovascular theory:

Pathophysiology

 The neurovascular theory:

Time Is Critical in Preventing Migraine From
Becoming Full-blown
Harvard Research Suggests:
A Sequence of Events Leads to Central Sensitization

Within minutes of a If migraine is left untreated, Central sensitization

migraine being those peripheral pain signifies full-blown migraine,
triggered, the peripheral neurons activate and when central neurons are
neurons that innervate sensitize central neurons, continually firing and the
meningeal blood vessels leading to central attack becomes more
become sensitized sensitization difficult to treat
 STAGES OF MIGRAINE

Phases of a Migraine Attack

Pre-HA Headache Post-HA

Intensity

Premonitory/ Aura Mild Moderate to Postdrome

Severe HA
Prodrome

Time

Adapted from Cady RK. Clin Cornerstone. 1999;1(6):21-32.

Prodrome
 Mood Changes
 Irritability, depression, sleepy, apathy
 Neurologic symptoms
 Yawning, photo/phonophobia, vision changes
 Constitutional symptoms
 Fatigue, pallor, fluid retention, myalgia
 Alimentary symptoms
 Hunger, anorexia, nausea, diarrhea
Aura

 15% of patients
 Episode of focal
neurologic changes
 Develop over 5 to 15
minutes & last up to 60
minutes
 Visual, weakness,
numbness, confusion
Headache

 Headache lasts hours to days

 Migraine head pain unilateral in 56 – 68% of patients
 90% of patients have coexisting nausea
 Constitutional symptoms common
Postdrome

 Depression
 Drowsiness
 Cognitive changes
 Memory loss
 Difficulty with concentration
Treatment philosophy

 If the pain can be stopped early, the cascade

of pain responses can be controlled
 Headache needs to be caught before central sensitization
occurs
 Patients may receive the greatest benefit
from their migraine medication if they:
 Practice early intervention
 Use a fast-acting migraine medication
General Treatment

 Avoid triggers!
 Maintain regular sleep schedule
 Maintain regular meal schedule
 Low tyramine
 Limit caffeine
 Avoid nitrates/nitrites/MSG
 Limit chocolate
 Reduce stress
 Adequate water intake
Treatment Options
Two Treatment Approaches
• Acute therapy
 Work quickly to relieve migraine pain and other
symptoms
 Are taken only at migraine onset

• Preventative therapy
 Prevent or reduce the number of migraine attacks
 Are taken on a daily basis
Migraine Abortives

 NSAIDs
 Triptans
 Acetaminophen/Butalbital/Caffeine
 OTC migraine preparations “Excedrin Migraine”
 DHE
Acute Treatment

 NSAIDS
 Inhibit prostaglandin formation, thus reducing inflammation
 Naproxen
 Ibuprofen
 ASA
 COX2 inhibitors
Acute Treatment

 Triptans
 Selective 5-HT1B/1D agonists
 Block actions of 5-HT such as dilation of cranial arteries/AV anastomoses, neurogenic dural
plasma extravasation
 Use early!
 More effective in mild/moderate pain
 Caution about rebound
Acute Treatment

 Triptans:
 Almotriptan (Axert)
 Eletriptan (Relpax)
 Frovatriptan (Frova)
 Naratriptan (Amerge)
 Rizatriptan (Maxalt)
 Sumatriptan (Imitrex)
 Zolmitriptan (Zomig)
Acute Treatment

 Triptans side effects:

 Chest pressure/heaviness
 Jaw tightness
 Dizziness
 Somnolence
 Fatigue
 Nausea
 Paresthesias
Acute Treatment

 Triptans
 Relative contraindication:
 Complicated migraine
 CAD, CVD, PVD
 Smoker + oral contraception
 Severe HTN
Acute Treatment

 Ergotamine tartrate
 Available for over 50 years
 Vasoconstrictors
 Oral, SL, IV, PR
 Caution about rebound, dependence
 Contraindicated:
 CVD
 CAD
 PVD
 Severe HTN
 Sepsis
 CKD
 Hepatic disease
 Pregnancy
Acute Treatment

 OTC agents
 Cautious of rebound!

 Opioids and butalbital are NOT considered appropriate abortive agents except in
cases of last resort. [US Headache Consortium]
Status Migrainosus

 Migraine lasting greater than 72 hours in duration

 Refractory to conventional treatment
 Steroid burst – oral methylprednisolone, prednisone
 “Headache cocktail”:
 Ketorolac 60mg IM
 Diphenhydramine 50mg IM
 Prochlorperazine 10mg IM
 Patient must have a driver
Prophylactic Treatment

 Indicated in patients with:

 >2 migraines per month
 Attacks lasting for several days per week
 Severity/frequency that critically impacts patient’s daily life
 Abortive therapies are contraindicated, ineffective, overused, not tolerated
 Uncommon migraine type (hemiplegic, basilar, prolonged aura, migrainous infarction)
Prophylactic Treatment

 Start low and go slow!

 Adequate trial with adequate dose
 Consider comorbid conditions when choosing a medication
 May add a second medication
Reduce Frequency

 Seizure Medications
 Topiramate, valproate, gabapentin, zonisamide
 Blood Pressure Medications
 Beta Blockers: propranalol, nadolol
 Ca+ Channel Blockers: verapamil
 Antidepressants
 Tricyclics: amitriptyline, nortriptyline
 Combos: venlafaxine
Botulinum Toxin

 FDA approved for chronic migraine

 Defined as headache present for 15 days per month or more
 Administered every 12 weeks
Other treatment options

 Magnesium glycinate 400mg bid

 Riboflavin 400mg daily
 Melatonin
 CoQ10
 Butterbur/Feverfew/Skullcap
 Acupuncture
 Biofeedback/Yoga/Meditation
Other treatment options

 Vagus Nerve Stimulation

 Spring TMS
 Transcranial magnetic stimulation
 Cefaly
 Tens-like unit
Emerging migraine therapy
Primary Most
Sponsoring Molecular Advanced
Company INN or Code Name Format Target Phase Indications
Alder
ALD403/ Humanized Migraine
Biopharmaceu CGRP Phase 3
eptinezumab IgG1 prevention
ticals
Migraine and
Eli Lilly and LY2951742/ Humanized cluster
CGRP Phase 3
Company galcanezumab IgG4 headache
prevention
Teva
TEV‐48125/ Humanized Migraine
Pharmaceutica CGRP Phase 3
frestanezumab IgG2 prevention
ls

Amgen/Novart AMG334/ CGRP Migraine

Human IgG2 Phase 3
is erenumab receptor prevention

Clin Pharmacol Drug Dev. 2017 Nov-Dec; 6(6): 534–547.

Tension-type Headache
 Tension-Type Headache:
Diagnostic Criteria
At Least 10 Episodes Fulfilling the Criteria Below
Headache Description of Headache Associated Symptoms
lasting Two of the following: Both of the following:
AND
30 minutes
to 7 days Pressing/tightening quality No nausea or vomiting
(nonpulsating)
Photophobia and
Mild or moderate intensity phonophobia are
(may inhibit, does not prohibit absent, or one but
AND activities) not the other
is present
Bilateral location

No aggravation by walking up
stairs or similar routine physical
activity

Olesen J. Cephalalgia. 1988;8(Suppl 7):1-96.

Treatment

 Acute
 NSAIDs
 Acetaminophen
 Muscle relaxers ?
 Chronic
 TCA
 Physical Therapy
 OMT
 Occipital Nerve Block
Cluster Headache
Cluster Headache: Diagnostic Criteria
At Least 5 Attacks Fulfilling the Criteria Below
Frequency Description of Headache Associated Symptoms
of attacks:
1 every All of the Following: AND One of the Following
other day Severe Present on the Pain Side:
to 8 per
day Unilateral orbital, Conjunctival Miosis
supraorbital, and/or injection
Ptosis
temporal location
Lacrimation
AND Lasts 15 to
Eyelid edema
Rhinorrhea
180 minutes
(untreated) Nasal congestion

Forehead and facial sweating

Olesen J. Cephalalgia. 1988;8(Suppl 7):1-96.

Cluster Headache

 Location: strictly unilateral, often periorbital or temporal

 Pain characteristics: constant, severe, burning, or boring
 Frequency: 1-6(+) per day
 Demographics: Males : Females  6 : 1
 Duration: 15-180 minutes
 Associated symptoms: autonomic symptoms – (ipsilateral to pain)
tearing, rhinorrhea, conjunctival injection, eyelid edema, ptosis,
pupillary miosis, restlessness
Cluster Headache

 Triggers: ETOH, REM sleep, diurnal or annual cycles

 Treatment:
 Abortive: high-flow oxygen, DHE, parenteral triptans
 Bridge therapy: steroids
 Prophylactic: Verapamil, Divalproex Sodium, Topirimate, Lithium
Summary

 Identify headache type

 Implement acute vs chronic therapies
 Avoid medication overuse