Chronic Daily HeadacheFebruary 13, 2013

Brian Plato, DO

Why is it important?

• Chronic headache disorders are among the top 20 causes of disability in the US according to the World Health Organization (WHO)

• 4% of Americans experience 4 hours of headaches per day, at least 15 days per month

• Headache disorders are responsible for more than $31B in economic costs in the US annually

What is it?

• Headache occurring more than 15 days per month for more than three months– Often times is daily

• Further divided into two subgroups– Headaches lasting more than four hours– Headaches lasting less than four hours

Where do we start?

• Realization– It is NOT normal to have a headache every day

How many people in this room have a bottle of Excedrin, Advil, Aleve, etc. in their purse

right now?

Meeting your doctor

• History• Examination• Testing– Neuroimaging (CT, MRI, etc)– Blood work– Ophthalmologic evaluation– Lumbar puncture

• Diagnosis• Management

Diagnosis

• Primary vs. secondary headache disorders• Primary headache disorders– “The headache is the thing”• Examples: migraine, tension-type, cluster

• Secondary headache disorders– The headache is caused by something else• Examples: medication overuse, cervical spine disease,

vascular disorders, trauma

Diagnosis• Primary headache disorders– Lasting >4 hours• Chronic migraine• Chronic tension-type headache•New daily persistent headache•Hemicrania continua

– Lasting <4 hours• Cluster•Other less common disorders

• Secondary headache disorders

Chronic Migraine• Headache on ≥15 days per month for at least 3 months– Has at least two of:

•Unilateral location• Pulsating quality•Moderate or severe pain intensity•Aggravation by or causing avoidance of routine physical activity (e.g.

walking or climbing stairs)– And at least one of:

•Nausea and/or vomiting• Light and sound sensitivity

– No medication overuse and not attributed to another causative disorder

Chronic Migraine

• Usually a prior history of episodic migraine• Eventually over time gradually develops in to a

daily pattern• May or may not be associated with medication

overuse

Why is this important for women’s health?

• Frequently stated that 18% of women have migraine

• But at mid-life is closer to 30%• By age 50, up to 40% of women have been

affected by migraine

What is migraine really?

• Rather complex and not fully understood• Neurons of individuals with migraine are

hyperexcitable• Migraneurs are more sensitive to external

stimulation– Some interesting evolutionary theories regarding

migraine

Migraine Aura

• A reversible focal neurological deficit– Most commonly visual

• Cortical spreading depression– Think a wave of activity moving across the brain

followed by decreased activity– The part of the brain inactivated causes the

neurological deficit• Occipital lobes = vision

The Headache• Trigeminal nerve and its blood supply

(neurovascular)– Release of neuropeptides

• CGRP• Substance P• 5-HT (serotonin) --> “triptans”• Nitric oxide

– Vasodilatation (CGRP) leads to further activation, and the process spreads

– Brainstem, thalamus, cortex become activated leading to “central sensitization”• Amplified pain signaling in the central nervous system

– Allodynia: pain due to a non-noxious stimulant

Secondary Headache Disorders

• Medication overuse headache (MOH)• Cervicogenic headache• Post-traumatic headache• Others

Medication Overuse Headache

• 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

• Headache resolves or reverts to its previous pattern within 2 months after discontinuation of overused medication

Medication Overuse Headache

• Generally believed to occur when medication usage exceeds 2-3 times per week

• Most patients have a history of episodic migraine that has transformed into a daily headache

• 80% of patients in a headache specialty clinic• Prior to diagnosis– Duration of primary headache: 20 years– Time of frequent medication intake: 10 years– Time of daily headache: 6 years

Medication Overuse Headache

• Simple analgesics:• Acetaminophen (Tylenol)• Ibuprofen (Advil, Motrin)• Aspirin (Bayer)• Naproxen (Aleve)

• Combination products:• Fioricet• Excedrin

• Opiates:– Lortab (hydrocodone)– Percocet (oxycodone)– Many others

• Triptans:– Imitrex, Maxalt, Relpax,

Zomig, Frova, Amerge, Axert, Treximet

• DHE

Medication Overuse Headache

The Cleveland Clinic Manual of Headache Therapy p. 156

Medication Overuse Headache

Bigal ME, et al. Headache. 2008;48:1157-1168.

Bigal ME, et al. Pain. 2009;142:179-182.

Medication Overuse Headache

• Serious consequences– May reduce effectiveness of other medications– Can cause kidney / liver problems– Tolerance – same dose becomes less effective– Dependence – physical need for medication•Withdrawal

Why opiates are bad

Medication Overuse Headache

Mathew N, et al. Headache. 1990;30:634-638.

Medication Overuse Headache

• Treatment– Must discontinue overused medication– Detoxification• Inpatient vs. outpatient

– Begin / adjust prophylactic medications– More appropriate rescue medications

Cervicogenic Headache

• Pain referred from a source in the neck and perceived in one or more regions of the head and/or face

• Evidence of a disorder or lesion within the cervical spine or soft tissues of the neck as a cause of headache

• Pain resolves within 3 months after successful treatment of the causative disorder or lesion

Post-Traumatic Headache

• Most patients with mild head injury are never hospitalized, so exact estimates hard to determine

• Estimated in 30-80% of patients with mild head injury

• Of patients with postconcussive syndrome up to 90% report headache

• 97% of patients with whiplash injury seeking medical attention also have headache

Post-Traumatic Headache

• At 3 months post-injury up to 78% have ongoing headache

• Most patients have headache remission within 6 months

• 12 months post-injury up to 35%• At 4 years 24%• 6 months seems to be the timeframe that if

still having symptoms will likely continue

Comorbidity of CDH

• Depression is 35 times more likely• Panic attacks and anxiety are three times more

likely• Sleep-related breathing disorders occur in up

to 30% of patients• These problems need to be considered and

addressed

CDH Treatment / Management

• Depends first on correct diagnosis• Not always as easy at is sounds

• Medications– Prescription and non-prescription

• Lifestyle modifications• Physical / behavioral therapies• Injections• Hospitalization• Surgical evaluation

Preventative Medications

Preventative Medications

• There are no “migraine specific” medications used in the prevention of migraine

• Use medications from other classes– Blood pressure medications– Antiseizure medications– Antidepressants– Serotonin antagonists– Vitamin supplements– Botox

Preventative Medications

• Important to identify patients that are using frequent rescue medications and may be on the way to developing medication overuse headache

• Patients who have disabling headache that is not easily treated with rescue medications

• Ideally treat multiple conditions with a single medication– ie. high blood pressure and migraine

Antidepressants

• Tricyclic antidepressants– Amitriptyline (Elavil)– Nortriptyline (Pamelor)– Protriptyline (Vivactil)

• Side effects– Elavil and Pamelor are sedating and taken at night

(useful for patients with sleep trouble)– Cause dry mouth, constipation, weight gain– At high doses can cause heart related issues that may

require an EKG to be checked

SSRI / SNRI• SSRI– Fluoxetine (Prozac)– Paroxetine (Paxil)– Fluvoxamine (Luvox)

• SNRI– Venlafaxine (Effexor)– Duloxetine (Cymbalta)– Desvenlafaxine (Pristiq)

• SNRIs tend to be more effective for migraine than SSRIs– Venlafaxine (Effexor) has the best evidence for use in

prevention of migraine

SSRI / SNRI

• Side effects– Weight gain– Sexual dysfunction– Sedation– Nervousness

Antiseizure Medications

• Recently have become most frequently used medications for prevention of migraine– Topiramate (Topamax)– Valproate (Depakote)– Gabapentin (Neurontin)– Zonisamide (Zonegran)

Topiramate (Topamax)

• One of the most frequently used medications in the prevention of migraine

• Has several advantages, but also does have some side effects to be aware of

• Effective in nearly 50% of patients that use it• Rather than weight gain, often times causes

weight loss• Optimal dose is 50mg twice per day– If side effects occur, sometimes may use nighttime only

dosing

Topiramate (Topamax)• Side effects

– Up to 13% of patients experience cognitive dysfunction of trouble with processing information and trouble finding words

– Numbness / tingling of fingers, toes, face• Actually a predictor of which patients will benefit from topiramate use• Potassium supplementation can help

– Risk of kidney stones– Glaucoma– Reduced sweating (important in athletes / overheating)

• Recently identified birth defects– Oral cleft (palate, lip) 11 times higher than general population– Rated as Category D for pregnancy

• Reduced oral contraceptive effectiveness– At doses greater than 200mg / day

Valproate (Depakote)• Quite effective, but less commonly used due to

side effect potential• Optimal dose is 500 – 1,500mg per day• Side effects– Weight gain– Hair loss– Pancreatitis– Liver problems

• Significant effects with women of child-bearing potential– Neural tube defects (ie. spina bifida)

Blood Pressure Medications

• Beta blockers• Calcium channel blockers• Other blood pressure medications– Not frequently used

• Useful in patients with co-existent high blood pressure

Beta Blockers• Propranolol• Timolol• Atenolol• Metoprolol• Nadolol– Lower blood pressure and heart rate

• Can lead to light-headedness– Can reduce aerobic capacity– Worsen asthma– Avoid in diabetics– Can worsen depression

Calcium Channel Blockers

• Verapamil• Diltiazem– Generally well tolerated– Often times more useful in patients with migraine

with aura– Side effects include light-headedness,

constipation, and swelling of legs

Vitamin Supplements• Not as well studied as prescription medications (product

of financing of studies)• Magnesium

– 400+mg / day– Diarrhea– Magnesium glycinate probably best tolerated form

• Riboflavin (B2)– 25 – 400mg / day– Will discolor urine

• Coenzyme Q10– 100mg 3x / day – I recommend 200mg 2x/day– Costly (sometimes)

• Butterbur and Feverfew also felt to be effective

Rescue Medications

• Primary goal is to achieve relief of pain, associated symptoms, and disability within 2 hours of use

• Goal is to use rescue medications 2 or fewer times per week to prevent developing medication overuse headache

Rescue Medications

• It is important to treat the headache as soon as possible, as time goes on the medications become less effective

• Allodynia is defined as pain resulting from stimulation that would not normally be perceived as noxious (ie. light touch of the skin)– To the patient this is perceived as scalp tingling or pain

when lightly touched during a migraine– To physicians this means that the deep parts of the

brain have been stimulated by the migraine attack and it is often times more difficult to treat

Rescue Medications

• Another note is that in treating migraine unlike treating other conditions (ie. high blood pressure) we often times suggest using higher dose medications initially and backing down the dose if side effects are experiences, rather than over time escalating doses– So it is important to understand what potential side

effects can occur with medications and understand that the goal is being pain-free with TOLERABLE side effects rather than being with pain and no side effects

Nonspecific Migraine Medications• Nonsteroidal Anti-inflammatory Drugs (NSAIDs)• Over 20 forms of NSAIDs available in the US, many

available over-the-counter• Have anti-inflammatory effects as well as analgesic (pain

relief) effects• Not processed through the liver• Kidney metabolism– Very important for patients with kidney disease, on

other medications that have effects on the kidneys, and in patients with extreme vomiting (dehydration can lead to kidney problems)

• Can lead to stomach bleeding with frequent use

NSAIDs

• Can be used alone or in combination with other medications (ie. triptans)

• Are non-sedating• Have been shown to be effective in treatment

of patients with allodynia• Because of the availability there is significant

problems with overuse, particularly leading to medication overuse headache

Acetaminophen• Acetaminophen (Tylenol)• Most people do not find useful for severe

migraine• Can be used for mild headache• Typical dose is 1000mg at onset of headache• Often times used in combination products (ie.

Fioricet, Midrin, etc)• Can lead to medication overuse headache• With heavy usage can lead to liver toxicity,

otherwise no significant side effects

Butalbital• Combination product• Butalbital / acetaminophen / caffeine

– Esgic, Fioricet• Butalbital / aspirin / caffeine

– Fiorinal• Side effects include incoordination, disinhibition, memory

problems, drowsiness• If used for extended periods of time and then

discontinued can cause withdrawal seizures• Significant risk of medication overuse headache

– Studies show when used as few as 5 times per month can lead to MOH

Excedrin• Combination of aspirin, acetaminophen, and caffeine• Can be used for mild to moderate migraine• Due to the multiple products combined there is

significant risk of medication overuse headache• Available OTC (unregulated by treating physicians

patients can take unlimited amounts)• In specialty headache clinics this is probably the

most frequently overused medication and causes more frequent headache

Anti-nausea medications

• Can often times alone or in combination be effective in treating migraine– Metoclopramide (Reglan)– Prochlorperazine (Compazine)– Promethazine (Phenergan) to a lesser extent

• Most common side effects are drowsiness and dizziness

• More significant side effects include dystonia (sustained muscle contraction) and akathisia (sense of restlessness) which can be treated with Benadryl

Opiates

• Worth mentioning, but in the hands of headache specialists are not frequently used

• In migraine, opiates are not well absorbed, they are associated with increased nausea, and sedation

• Very quickly can lead to physical dependence and are quite notorious for causing medication overuse headache

Migraine specific medications

Triptans

• Introduced in the 1990s• Often times considered the drug of choice in

treating migraine• Selective agonists (activators) of serotonin

blocking the release of other inflammatory chemicals during a migraine attack

Triptans

• Available in many different brand names with varying time of onset and duration of action

• Available in a variety of delivery methods– Oral tablet– Oral disintegrating– Nasal– Injection– Patch (in development)

Triptans• Side effects– Narrow coronary blood vessels by 10-20% (cannot be

used in individuals with a history of coronary or cerebro-vascular disease or uncontrolled risk factors)

– Tightening of the throat, chest, jaw, neck, and limbs– Numbness of the limbs and around the mouth– Hot and cold sensations

• Thought to be due to esophageal (not heart) related spasm and muscle contractions

• If warned in advance, most patients can tolerate side effects with the benefit that they give

Triptans• “Patients vary more than triptans”• Meaning, just because one did not help or caused

side effects does not mean that another will do the same– I give the example of Coke and Pepsi – it’s basically the

same stuff but some people like one and some people like another, and you won’t know until you’ve tried them

• Or that different routes of administration won’t have a different effect

Triptans

Sumatriptan• Imitrex, Statdose, Sumavel, Alsuma• First triptan brought to market (1991)• Available oral, nasal, subcutaneous injection and soon patch• Available as a generic• Oral dose is 25, 50, 100mg – maximum per 24 hours is 200mg

– Available in combination with naproxen as Treximet• Subcutaneous (SC) forms (Statdose, Sumavel, Alsuma) are 4 and

6mg (max 12mg / 24 hours)– Have much quicker onset of action (10 minutes) and are great

for patients with significant nausea and vomiting– Statdose and Alsuma use a needle, Sumavel is needle-less

Ergots

• Ergotamine tartrate available since 1925• Dihydroergotamine (DHE) more refined

version available since 1945– These were the only available migraine specific

medications until triptans introduced in 1990s

• Effect many chemicals in the nervous system which explains why they are so effective, but also explains the side effects

Ergots / DHE• Nausea is the major side effect

– May actually increase nausea of migraine rather than improve it• Again contraindicated in patients with vascular disease,

coronary artery disease, etc.• Available IV (hospital use)• Intramuscular – can be administer at home• Intranasal (Migranal) – very easy to use at home

– Inhaled in each nostril and then repeated in 15 minutes– Much less effective than IV / IM

• Orally inhaled DHE (Levadex) coming to market soon– Inhaled orally at home with blood levels as high as IV, but with

less nausea

Lifestyle Modifications• Diet– Tyramine containing foods• Cheeses: blue, cheddar, parmesan, swiss

– MSG– Nitrates• Processed foods / meats

– Chocolate– CAFFEINE• About two per day

– Water• More than 2.5 liters per day

Lifestyle Modifications• Sleep– Too much (>8.5 hours) and too little (<6 hours)•Maintain regular sleep schedule

– Snoring / not rested after sleep• Sleep apnea

– Relaxation techniques for sleep– Avoid caffeine, alcohol, nicotine– Avoid “activating” activities in bed• TV, phone, video games

Physical / Behavioral Modifications• Physical therapy

•Normalize the musculoskeletal system as much as possible in order to reduce stress and tension on soft tissues and joints

• Biofeedback•Method of gaining control of the body processes to

increase relaxation, relieve pain, and develop healthier, more comfortable life patterns

• Progressive muscle relaxation• Technique that teaches you to concentrate on relaxing

every muscle in your body

Injections

• Occipital nerve block– Combination of local

anesthetic (lidocaine) and steroid

– Studies vary, but up to 50% of patients report improvement

Injections

• Botox– Patients with 15 or more

days of migraine per month

– Up to 9 days less per month of headache

– Patients on opiates and butalbital did worse

– FDA approved

Botox

• OnabotulinumtoxinA• Famous for being used for “wrinkles”• Found to be effective in patients with chronic

migraine– Greater than 15 days of headache per month for

greater than 3 months• In clinical trials patients using opiates and

butalbital were excluded as they tend to do worse

Botox

• 155 units injected into 31 sites given every 3 months

• Minimal side effects– Injection site pain is largest

• Up to 9 days less per month of headache• FDA approved

Outpatient Infusion Therapy

• Treatment with IV infusions of medications under direction of physician

• Outpatient• Break the daily cycle• Transition to new therapies

Hospitalization

• Management of withdrawal from overused medication

• Repeated infusions of IV medications

• Adjustment of prophylactic medications

Prognosis / Outcome

• Goal is to transition from daily headache to episodic

• Studies report up to 80% of patients can have a 50% reduction in headache at 2 years

• Many of these patients require inpatient management initially

What can you do?

• Track headaches• Paper diary• iHeadache• www.iheadache.com• Evaluate lifestyle factors• Diet• Caffeine• Sleep

What can you do?

• Evaluate medicine use• Work with your physician• Set reasonable expectations• Not a cure, management

What can you do?

• Get involved!• Headache school• Alliance for Headache Disorders Advocacy• American Headache Society (AHS) Committee for

Headache Education (ACHE)

Headache School

• What is a migraine?– March 14

• Medication maze– April 11

• How diet affects headaches– May 16

• Women and Headaches– June 13

What can you do?• American Headache Society Committee for Headache Education• www.achenet.org

• American Headache Society• http://www.americanheadachesociety.org

• The International Headache Society• www.i-h-s.org

• OUCH - Organization For The Understanding Of Cluster Headache• www.ouch-us.org

• Southern Headache Society• www.southernheadache.org

• Alliance for Headache Disorders Advocacy• www.allianceforheadacheadvocacy.org

What can we do for you?

• Outpatient neurologists / headache specialists• 629-1234• Inpatient neurologists / headache specialists• IV infusion services• Elective hospitalization• Occipital nerve blocks• Botox• Psychological counseling • Neurosurgical consultation

Thank you!

Questions?