Headache

disorders
Debalke D.
Lecturer, AMU
 Definition

• A headache is pain or discomfort in the

head or face area.
• Types of headaches include
– migraine, tension, and cluster.

2
Migraine - Definition
 “Migraine is a familial disorder
characterized by recurrent attacks of
headache widely variable in intensity,
frequency and duration.
 Attacks are commonly unilateral and are
usually associated with anorexia, nausea
and vomiting”
-World Federation of Neurology
Migraine Facts
• Migraine is ……..
– one of the common causes of recurrent headaches
• According to International Headache Society/IHS,
migraine constitutes ………..
– 16% of primary headaches
• Migraine afflicts …10-20% of the general population
• More than 2/3 of migraine sufferers either have
……..
– never consulted a doctor or have stopped doing so
• Migraine is ………underdiagnosed and undertreated
• Migraine greatly affects quality of life.
• The WHO ranks migraine among …………
– the world’s most disabling medical illnesses
Burden Of Migraine
• World
– 15-20% of women
– 10-15% of men
• Adults
– Female: Male ratio is 2 : 1(A drop in estrogen
levels can trigger a headache.)
• Childhood migraine
– boys and girls - until puberty….affected
equally
– After puberty …..more shift to girls
NEJM 2002; 346(4): 257-269; XI Congress of the IHS, 2004
Headache in the Population
• 99% of women and 93% of men have had
headache during their lifetime
• 25% of women and 8% of men in the
United States have had migraine
headache
• 18% of women and 6% of men have had
migraine over the previous year
• Prevalence is highest between age 25 – 55
years
• In the U.S.
– An estimated 30 million have migraine and …
– up to 10 million have chronic daily headache
Migraine, chronic tension-type
headache, and cluster headache in an
Ethiopian rural community
• 15,500 adults (> or = 20 years) in a rural
district in Ethiopia studied for chronic headache.
• The 1-year prevalence of migraine headache
was 3.0% (4.2% for females and 1.7% for
males) with the peak age specific rate in the
fourth decade.
• Migraine headache was about three times
more common in females than in males at
any decade.
• Family occurrence of migraine in first-degree
relatives was 30%.
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Causes of Migraine
• Increased excitability of CNS
• Meningeal blood vessel dilation
• Activation of perivascular sensory
trigeminal nerves
• Pain impulses
• Vasoactive neuropeptides contain:
– substance P
– calcitonin gene-related peptide (CGRP)
– neurokinin A
• combination of increased pain sensitivity,
tissue and vessel swelling, and
inflammation
Interaction in Brain
Nerve signals travel to the pain nuclei in the
brain stem, where the sensation of pain is
processed
• pain of a migraine
arises between the
skull and the brain
tissue
• 3 meningeal
membranes
•dura mater
•arachnoid membrane
•pia mater
 Classification of headaches
• Primary • Secondary
Headaches Headaches
• OR Idiopathic • OR Symptomatic
Headaches Headaches
– The headache is – The Headache Is Only
itself the disease A Symptom Of
Another underlying
– No organic lesion in
disease
the background
– Treat the underlying
– Treat the headache! disease!
SECONDARY, SYMPTOMATIC
HEADACHES
• THE HEADACHE IS A SYMPTOM OF AN
UNDERLYING DISEASE, LIKE
– Hypertension - Sinusitis
– Glaucoma - Eye strain
– Fever
– Anaemia - Temporal arteriitis
– Meningitis, encephalitis
– Brain tumor, meningeal carcinomatosis
– Haemorrhagic stroke…
 Primary, idiopathic
headaches

1. Tension type of headache

2. Migraine
3. Cluster headache
4. Other, rare types of primary
headaches
Primary, idiopathic
headaches…

13
 Tension headache
• Renamed as…….. tension-type headaches by
the International Headache Society in 1988
• Is the most common type of
primary headaches.
• The pain can radiate from the neck, back,
eyes, or other muscle groups in the body.
• It account for …….
– nearly 90% of all headaches.
• Approximately 3% of the population has …….
– chronic tension-type headaches
Tension –type headaches
• Can be episodic or chronic.
• Episodic tension-type headaches occur
…….
– 15 days a month.
• Chronic tension-type headaches ……..
– 15 days or more a month for at least 6
months.
• Can last from minutes to days, months or
even years, though a typical tension
headache lasts 4-6 hrs
Cluster headache
• Nicknamed - "suicide headache“
• Neurological disease that involves an
immense degree of pain.
• "Cluster" - occur periodically, with active
periods interrupted by spontaneous
remissions.
• Cause ……….unknown
• Prevalence - 0.1% of the population
• Gender - men affected the most vs.
women
 Migraine Triggers
• Food:Alcohol,Caffeine/ • Visual stimuli
caffeine
• Auditory stimuli
withdrawal,Chocolate,
Fermented food etc… • Olfactory stimuli
• Disturbed sleep pattern • Weather changes
• Hormonal changes • Hunger
• Drugs • Psychological
• Physical exertion factors
• Stress
Phases of Acute Migraine
• Prodrome

• Aura

• Headache

• Postdrome
PRODROME
• Vague premonitory symptoms that
begin from..
– 12 to 36 hours before the aura and
headache
• Symptoms include……..
– Yawning
– Excitation
– Depression
– Lethargy
– Craving or distaste for various foods
Duration – 15 to 20 min
AURA
• Aura is ……….a warning or signal before
onset of headache
Symptoms
• Flashing of lights
• Zig-zag lines
• Difficulty in focusing
Duration : 15-30 min
HEADACHE

• Headache is generally unilateral and

is associated with symptoms like:
– Anorexia
– Nausea
– Vomiting
– Photophobia-fear of light
– Phonophobia-fear of sound
– Tinnitus-a ringing sound
• Duration is 4-72 hrs
POSTDROME (RESOLUTION
PHASE)

Following headache, patient complains

of
• Fatigue
• Depression
• Severe exhaustion
• Some patients feel unusually fresh
Duration: Few hours or up to 2 days
MIGRAINE –
CLASSIFICATION

According to Headache Classification Committee

of the International Headache Society, Migraine
has been classified as:

[Link] without aura (common

migraine)
[Link] with aura (classic migraine)
[Link] migraine
MIGRAINE: CLINICAL
FEATURES

Migraine Without Migraine With Aura

Aura
No aura or Aura or prodrome is
Prodrome present
Unilateral throbbing Unilateral throbbing
headache may be headache and later
accompanied by becomes
nausea and generalised
vomiting
During headache, Patient complains of
patient complains of visual disturbances
 MIGRAINE -
PATHOPHYSIOLOGY

VASCULAR THEORY
•Father of neurology, “Thomas Willis”….
proposed the vascular theory…….
•Dilatation of blood vessels in the head was
the cause of migraines
•when pressure was applied to the
superficial temporal artery, the patient
improved
 MIGRAINE -
PATHOPHYSIOLOGY

SEROTONIN THEORY
•Decreased serotonin levels linked to
migraine
• Specific serotonin receptors found in the
blood vessels of the brain
PRESENT UNDERSTANDING
•Neurovascular process, in which neural
events result in activation of blood vessels,
 MIGRAINE: DIAGNOSIS
• Medical History
• Headache diary
• Migraine triggers
• Investigations (only to exclude secondary
causes)
EEG
CT Brain
MRI
• Common misdiagnoses for migraine:
– Sinus Headache
– Stress
 Migraine Remembered
S evere
U ni-
L ateral 2 of 1st 4
T hrobbing
A ctivity worsens HA
N ausea
S ensitive to light/sound 1 of last 2
Headache is episodic, and usually lasts 4-72
hours
DIFFERENTIATING COMMON PRIMARY
HEADACHES

Strictly unilateral
 Tension headaches: Do not have the associated
features like nausea, vomiting, photophobia,
phonophobia.
 The muscle contraction leads to headache.
 Usually bilateral. Intensity is mild or moderate
 Cluster headaches: Severe unilateral pain.
 Headache associated with lacrimation, nasal congestion,
rhinorrhea, facial sweating or eyelid edema.

• The International Headache
Society (IHS) classifies migraine
headache
• The IHS defines the intensity
of pain with
Number
a verbal, four-point
Pain Annotations
scale:
0 NO
1 Mild does not interfere with
usual activities
2 Moderate inhibits, but does not
wholly prevent usual
activities
3 Severe prevents all activities
 LONG-TERM TREATMENT GOALS FOR
THE MIGRAINE SUFFERER

• Reducing …..the attack frequency and

severity
• Avoiding …escalation of headache
medication
• Educating and enabling the patient to
manage the disorder
• Improving the patient’s quality of life
Non-pharmacologic treatments

• Application of ice to the head

• Bed rest or sleep, usually in a dark, quiet

environment
• Identification and avoidance of factors that
provoke migraine attacks
• Behavioral interventions (relaxation therapy,
cognitive therapy)
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MIGRAINE MANAGEMENT

• Pharmacotherapy

– Abortive therapy(acute therapy)

• non-specific

• specific

– Preventive(prophylactic)
therapy
34
 MIGRAINE: ABORTIVE
THERAPY
Non-specific treatment
Drug Dose Route
Aspirin 500-650 mg Oral
Paracetamol 500 mg-4 g Oral

Ibuprofen 200- 300 mg Oral

Diclofenac 50-100 mg Oral/IM
Naproxen 500-750 mg Oral
 ABORTIVE THERAPY FOR
MIGRAINE

Specific treatment
Drug Dose Route
Ergot alkaloids
Ergotamine 1-2 mg/d; max-6 Oral
g/d
Dihydroergotam 0.75-1 mg SC
ine
5-HT receptor agonists
Sumatriptan 25-300 mg Orally
6 mg SC
Rizatriptan 10 mg Orally
ANTI-NAUSEANT DRUGS FOR MIGRAINE
TREATMENT

Drug Dose Route

(mg)/d
Domperidone 10-80 mg Oral
Metocloprami 5-10 mg Oral/IV
de
Promethazine 50-125 mg Oral/IM
Chlorpromazin 10-25 mg Oral/IV
e
Ergots

• 1868: use of ergot in the treatment of

one-sided headache

• Ergot: potent neurotoxin & vasoconstrictor

found in a fungus that grows on rye

• 1940’s: ergotamine tartrate became the

preferred treatment for acute migraine

 Ergotamine
• Structurally similar to amines,
serotonin, norepinephrine, and
dopamine
• interact with multiple receptors
in these systems
• wide-range of effects
• cause constriction of the blood
vessels
• avoid if patient has coronary disease; safety
margin is small; overdose
Serotonin
• Neurotransmittor

• Serotonin ( 5- hydroxytryptamine) is thought to be

an important mediator of migraine.
• Unstable serotonergic neurotransmission

– has lower threshold for migraine.

• There are 7 classes of 5-HT receptors

• Out of 7, 2 involve in migraine pain.

Abortive therapy - Tritpans
5 Triptan Family - 5-HT1 receptor agonists
Examples-
• Sumatriptan – Imitrex
•Zolmitriptan – Zomig
•Rizatriptan – Maxalt
•Eletriptan – Relpax
•Naratriptan – Amerge
•Frovatriptan (Frova)
•Almotriptan (Axert)
Triptan side effects/risks
• Common…….sedation, nausea, muscle
ache, chest tightness (2 – 5%)
• Contraindications………CAD, CVA, PVD
• CAD – Coronary Artery Disease
• CVA – Cerebro vascular Accident
• PVD – peripheral vascular disease

• hemiplegic/basilar migraine
• Risk of serious cardiac event with
triptans is ~
– 1:1,000,000
Sumatriptan
• The first selective serotonin agonist
approved for the treatment of migraine
• Triptans are an advance over ergots
• Acts on receptors at smooth muscle cells
of brain vessels (also in peripheral blood
vessels like coronary artery = side
effects)
• 3 dosage forms: oral, nasal, & parenteral
• Rapid relief
Zolmitriptan
• Better……..oral bioavailability to
~50% (sumatriptan 14%)

• Half-life of 3 hours

• take orally at ……..the onset of

headache pain
Naratriptan
• Oral bioavailability improved to
~60%
• Longer half-life of 5-6 hours

• take orally at the onset of headache

pain
rizatriptan

• Oral bioavailability ~40%

• Shorter half-life of 2.5 hours ……..but

• shows the fastest time of onset!

 Triptans
• For faster onset…use.
– sumatriptan and zolmitriptan nasal sprays in 15 minutes.
– Sumatriptan injection starts working in 10 to 15 minutes

• Orally disintegrating tabs (Maxalt-MLT, Zomig-ZMT)

– Dissolve in the mouth, but are then swallowed and
absorbed in the GI tract.
– Work faster than other oral tabs
– For patients who can't take the oral tabs due to nausea
and vomiting.
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Triptans
• Longer duration.
– Frova (frovatriptan) and Amerge (naratriptan)
– longest-acting triptans...but also have the lowest
onset
• Combo therapy. Combining a triptan and an
NSAID
– Treximet (sumatriptan/naproxen)
• Medication overuse headaches ……..
– can occur with any of the acute migraine
drugs...triptans, analgesics, caffeine.
• If patients need an acute drug more than two
days a week, suggest …………prophylactic
therapy
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Ergot and Triptan
comparison
• The rates of ergotamine and
sumatriptan overuse were ………
– 14.2% and 3.5%, respectively

• Drug-induced headache could be found

more frequently in cases of ……..
– ergotamine overuse than triptan
 Abortive care strategies
• Stepped Approach…….Start with lower level drugs, then
………
– switch to more specific drugs if symptoms persist or worsen.

• Drugs……..
– Analgesics –NSAIDs…

– Vasoconstrictors – sympathomimetics…

– Opioids (try to avoid) - Butorphanol

– Triptans – sumatriptan (oral, SQ, nasal), naratriptan, rizatripatan,

zomatriptan.
– Limited by patient compliance.
 Abortive care strategies
• Stratified
– Adjusts treatment according to symptom
intensity.
• Mild – analgesics, NSAIDs
• Moderate – analgesic plus
caffeine/sympathomimetic
• Severe – opioids, triptans, ergots…
– Severe sx treatment limited due to
concomitant GI sx’s.
• Staged
– Bases treatment on intensity and time of
attacks.
– HA diary reviewed with patient.
– Medication plan and backup plans.
Acute Migraine Therapiesa
Medication Dosage Comments
Analgesics
Acetaminophen 1,000 mg at onset; repeat Max. daily dose is 4 g
every 4–6 hours as needed
Acetaminophen 250 2 tablets at onset and every 6 Available over-the-counter as
mg/aspirin 250 mg/caffeine hours Excedrin Migraine
65 mg
Aspirin or acetaminophen 1–2 tablets every 4–6 hours Limit dose to 4 tablets/day
with butalbital, caffeine and usage to 2 days/week
Isometheptene 65 2 capsules at onset; repeat 1 Max. of 6 capsules/day and 20
mg/dichloralphenazone 100 capsule every hour as needed capsules/month
mg/acetaminophen 325 mg
(Midrin)
Nonsteroidal antiinflammatory drugs
Aspirin 500–1,000 mg every 4–6 Max. daily dose is 4 g
hours
Ibuprofen 200–800 mg every 6 hours Avoid doses >2.4 g/day
Naproxen sodium 550–825 mg at onset; can Avoid doses >1.375 g/day
repeat 220 mg in 3–4 hours
Diclofenac potassium 50–100 mg at onset; can Avoid doses >150 mg/day 56
repeat 50 mg in 8 hours
Ergotamine tartrate Dosage Comments
Oral tablet (1 mg) with 2 mg at onset; then 1–2 Max. dose is 6 mg/day or 10
caffeine 100 mg mg every 30 minutes as mg/week; consider
needed pretreatment with an
antiemetic
Sublingual tablet (2 mg)
Rectal suppository (2 mg) Insert 1/2 to 1 suppository Max. dose is 4 mg/day or 10
with caffeine 100 mg at onset; repeat after 1 mg/week; consider
hour as needed pretreatment with an
antiemetic
Dihydroergotamine
Injection 1 mg/mL 0.25–1 mg at onset IM, IV Max. dose is 3 mg/day or 6
or subcutaneous; repeat mg/week
every hour as needed
Nasal spray One spray (0.5 mg) in each Max. dose is 3 mg/day;
nostril at onset; repeat prime sprayer 4 times
sequence 15 minutes later before using; do not tilt
(total dose is 2 mg or 4 head back or inhale through
sprays) nose while spraying; discard
open ampules after 8 hours
57
Serotonin agonists (triptans) Dosage Comments
Sumatriptan Injection 6 mg subcutaneous at onset; Max. daily dose is 12 mg
can repeat after 1 hour if
needed

Oral tablets 25, 50, 85 or 100 mg at onset; Optimal dose is 50–100 mg;
can repeat after 2 hours if max. daily dose is 200 mg;
needed combination product with
naproxen, 85 mg/500 mg
Nasal spray 5, 10, or 20 mg at onset; can Optimal dose is 20 mg; max.
repeat after 2 hours if needed daily dose is 40 mg; single-
dose device delivering 5 or 20
mg; administer one spray in
one nostril
Zolmitriptan Oral tablets 2.5 or 5 mg at onset as regular Optimal dose is 2.5 mg; max.
or orally disintegrating tablet; dose is 10 mg/day Do not
can repeat after 2 hours if divide ODT dosage form
needed
Nasal spray 5 mg (one spray) at onset; can Max. daily dose is 10 mg/day
repeat after 2 hours if needed
Naratriptan 1 or 2.5 mg at onset; can Optimal dose is 2.5 mg; max.
repeat after 4 hours if needed daily dose is 5 mg 58
Miscellaneous Dosage Comments
Butorphanol nasal spray 1 spray in 1 nostril (1 mg) Limit to 4 sprays/day;
at onset; repeat in 1 hour consider use only when
if needed nonopioid therapies are
ineffective or not
tolerated
Metoclopramide 10 mg IV at onset Useful for acute relief in
the office or emergency
department setting

Prochlorperazine 10 mg IV or IM at onset Useful for acute relief in

the office or emergency
department setting

a
Limit use of symptomatic medications to 2 or 3 days/week when
possible to avoid medication-misuse headache.

59
WHY THE NEED FOR PROPHYLAXIS
?
• Abortive drugs should not be used …….
– more than 2-3 times a week
• Long-term prophylaxis improves ……..
– quality of life by reducing frequency and
severity of attacks
• 80% of migraineurs may require
prophylaxis
WHEN IS PROPHYLAXIS
INDICATED?
According to the US Headache Consortium Guidelines,
indications for preventive treatment include:
• Patients who have very frequent headaches (more than 2
per week)
• Attack duration is > 48 hours
• Headache severity is extreme
• Migraine attacks are accompanied by prolonged aura
• Unacceptable adverse effects occur with acute migraine
treatment
• Contraindication to acute treatment
• Migraine substantially interferes with the patient’s daily
routine, despite acute treatment
• Special circumstances such as hemiplegic migraine or attacks
with a risk of permanent neurologic injury
Prophylactic…

• Selection of prophylactic therapy depends

on
– Efficacy

– Comorbid conditions

– Side-effect profiles

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 Prophylactic…

• Prophylaxis should be initiated with low doses and

advanced slowly until a therapeutic effect is achieved
or side effects become intolerable.
• Prophylaxis is usually continued for at least 3 to 6
months after headache frequency and severity have
diminished, and then gradually tapered and
discontinued, if possible.

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Treatment algorithm for prophylactic management of
migraine headaches

64
 PREVENTIVE THERAPY FOR
MIGRAINE
• Beta-blockers (propranolol, timolol, etc)
– ‘Gold standard’ in migraine prophylaxis
– Well established efficacy and safety in
migraine prophylaxis
– Preferred especially…….if hypertension or
anxiety co-exist
– Watch for……….fatigue and exercise
intolerance
– Limit rizatriptan (Maxalt) to just 5 mg per
dose in pts using propranolol b/c it can
increase levels of rizatriptan 65
 PREVENTIVE THERAPY FOR
MIGRAINE
• Amitriptyline and other tricyclics also help
but caution…
– dry mouth, constipation, and sedation
– Consider if ……insomnia, anxiety, or depression
present
– Recommend…….combining low doses of a BB
and TCA

• Topiramate is popular – effect on

weight(loss)
– But impair cognition and lower the efficacy of
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oral contraceptives.
 PREVENTIVE THERAPY FOR
MIGRAINE
• Divalproex - teratogenic...
– And can cause…….drowsiness, nausea, weight gain,
and hair loss

• Verapamil, lisinopril, candesartan, or gabapentin

– second-line because there's less evidence they
work.
– Caution ….. using an ACE inhibitor or ARB in women
who might get pregnant.
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 Prophylactic migraine therapies
Medication Dose

Adrenergic antagonists Atenolol 25–100 mg/day

Metoprolola 50–200 mg/day in divided
doses

Nadolol 80–160 mg/day

Propranolola,b 80–240 mg/day in divided
doses

Timololb 20–60 mg/day in divided

doses

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 Prophylactic migraine therapies…
Antidepressants Dose

Amitriptyline 25–150 mg at bedtime

Doxepin 10–300 mg at bedtime
Nortriptyline 10–150 mg at bedtime
Protriptyline 5–60 mg at bedtime
Fluoxetine 10–80 mg/day
Venlafaxinea 75-225 mg/day
Anticonvulsants Gapapentin 900–2,400 mg/day in divided
doses
Topiramateb 100 mg/day in divided doses

Valproic acid/divalproex 500–1,500 mg/day in divided

sodiumb doses
CCB Verapamila 240–480 mg/day in divided doses
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 Prophylactic migraine therapies…
Nonsteroidal antiinflammatory drugsc Dose
Ketoprofena 150 mg/day in divided
doses
Naproxen sodiuma 550–1,100 mg/day in
divided doses
Coenzyme Q10 300 mg/day in divided
doses
Feverfew 10–100 mg/day in divided
doses
Magesium gluconate 400–600 mg/day in
divided doses
Petasites 150 mg/day in divided
doses
Vitamin B2 400 mg/day
a
Sustained-release formulation available.
b
FDA approved for prevention of migraine.
c
Daily or prolonged use limited by potential toxicity. 70
Evaluation of therapeutic outcome

• Monitor for frequency, intensity, duration and change in

pattern of headache.
• Monitor for frequent use of medications, compliance, and
for side effects of medications.
• Patients should be encouraged to keep a headache
diary to document the frequency, severity, and duration
of migraine attacks, as well as response to medication
and potential trigger factors.
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Thank you!!!!

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