Migraine and Chronic Daily Headache Merle Diamond M.D.
Migraine Prevalence (American Migraine Study II) There are currently 28 million migraine sufferers age 12+ in the United States 21 million females 7 million males One in 4 households has at least 1 migraine sufferer Migraine prevalence peaks in the 25-55 age range Lipton et al. Headache. 2001;41:638-657.
The Burden of Migraine 28 million affected 50 percent are diagnosed 1 in 6 women 17 billion in lost workdays 150,000 bedridden each day
Headache Prevalence 100% % of Population 80% 75% 80% 60% 60% 40% 40% 25% 20% 0% Ever Had HA 12% Episodic HAs Severe HAs 5% IHS Migraine 20% Cumulative Direct HA Cost 100% 90% CDH 0% Primary Care Network
2004 AMPP Prevalence vs Historical Data With Similar Methodology 1989 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% 1999 2004 17.6% 18.2% 17.1% 12.1% 12.6% 11.7% 5.7% Total 6.5% Males 5.6% Females One- Year Period Prevalence for Those Age 12 Stewart WF et al. JAMA. 1992;267:64-69; Lipton RB et al. Headache. 2001;41:646-657.
Prevalence of Migraine Migraine Prevalence (%) 30 Age & Sex Females Males 25 20 15 10 5 0 20 30 40 50 60 70 80 Age (in years) Peak prevalence at age 40 years Greatest impact on ages 25 to 55 years 100
Headache Time Course Minutes Minutes Days Days Weeks/Months Weeks/Months Months/Years Months/Years Vascular Infectious Inflammatory/Neoplastic Secondary Headaches Primary Headaches
Red Flags Comfort Signs First or worst Abrupt onset Fundamental pattern change New headache pattern when 5 years old 50 years old Cancer, HIV, pregnancy Abnormal physical exam Neuro symptoms one hour Headache onset: with seizure or syncope with exertion, sex or valsalva Source: Cady RK, Schreiber CP, Unpublished. Stable pattern Long-standing history Family history of similar headaches Normal physical exam Consistently triggered by: Hormonal cycle Specific foods Specific sensory input Light Odors Weather changes
Pitfalls in the Diagnosis of Primary Headaches Rarely due to secondary/underlying etiology Pathophysiological preconceptions Muscle = tension Vascular = migraine Nasal symptoms = sinus headache Patient-directed diagnosis It s my allergies stress sinuses Symptom assessment distorted by medications Partially treated headaches may have blunted symptoms or partially treated migraine
MRI vs CT Chronicity Posterior fossa Vascular abnormality-nonruptured Fresh bleeding Edema New focal findings
Working up the Headache Patient History Most important of all! Exam General and neurological Lab Basics if warranted; ESR if over 60 years Neuroimaging Not routinely warranted Consider if: first or worse, change in pattern Abnormal exam, under age 5 and over age 50, history of trauma Neurology. 1994;44:1353-1354. CT head vs. CT sinus vs. MRI
The Symptom-based Approach to Diagnosing Migraine At least 5 attacks 4 to 72 hours Pain (2 of 4) Unilateral location Pulsating quality Moderate or severe intensity Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs) In addition (1 of 2) Nausea and/or vomiting Photo and phonophobia No evidence of organic disease International Headache Society. Cephalalgia. 2004;24 (Suppl. 1):24-27.
Case Study 16 year old boy with onset of headaches at 9. Approximately 3/month. Prodrome of neck tightness which leads to neck cracking. Tic disorder Anxiety disorder
Prevalence 100% 92% Neck Pain During Migraine 75% of subjects 80% 61% Descriptions 69% - tightness 17% - stiffness 5% - throbbing 5% - other Prior diagnosis 60% 41% 40% 20% 0% 82% - tension Prodrome Headache Postdrome Migraine Phase N = 144 Kaniecki R. Neurology. 2002;58(Suppl 6):S15-S20.
Case Study 56 year old female with chronic daily headache for 12 years after a serious sinus infection. S/P 2 sinus sx and multiple infections. Takes 10-12 OTC and 6-8 vicoprofen per day. Headaches are bilateral and diffuse No prior history of headache
Nasal and Ocular Symptoms Can Accompany Migraine Attacks Autonomic Symptoms 45% 45% of patients had at least 1 autonomic symptom during migraine attacks Barbanti et al. Cephalalgia. 2001;21:295. Nasal Nasal 21% & Ocular 45% Ocular 34% Of these... 45% had both nasal & ocular symptoms 21% had only nasal symptoms 34% had only ocular symptoms
History Onset Character of Pain Severity Duration Location Associated symptoms Prodrome Prior history/tests/ treatment Medications for present headache Family history Exertional aspects Number of headache days /month
The Easy List Do you have recurrent headaches like this? How many days/month do you have headaches? Is this your first/worst headache? What have you taken for this headache? What work-up have you had in the past? Do you take medicine for your
P.I.N. the Diagnosis on the Migraine Sufferer ID MigraineTM screener validated in primary care setting Three items (any two of the three items) Photophobia Impact (headache related disability) Nausea Sensitivity 0.81, specificity 0.75 Positive predictive value = 93.3% Lipton R, et al. Neurology. 2003;61:375-382.
Clinical Expressions of Migraine Migraine Menstrual One Neurological Process Tension Sinus
5 Phases of Migraine Pre-Headache Prodrome Headache Post-Headache Aura Postdrome Mild 2000 Primary Care Network, Inc. 2000 Primary Care Network, Inc. Moderate Severe Rescue
Various Premonitions and Prodromes Feeling of wellbeing Talkativeness Surge of energy Hunger Anorexia Yawning Photophobia Drowsiness Depression Irritability Tension Restlessness Neck pain Nausea
Prodrome: Symptoms uirritability - 48% unausea - 43% umuscle pain or tenderness - 38% uchange in energy level - 30% uchange in mood - 24% usleepiness - 22% uchange in appetite - 21% uyawning - 21% Luciani, R et al Cephalalgia 2000;20:122-126
Phase II Aura Headache Pre-Headache Prodrome Post-Headache Postdrome Aura Mild Moderate Severe Rescue 10% - 20% of patients Onset over 5 to 20 minutes Duration usually 1 hour or less May occur without HA Visual - most common Other - tingling, numbness, weakness, clumsiness, speech disorder
Classical Migraine Typical fortification illusion of migraine
Teichopsia
Phase III Early - Headache Headache Pre-Headache Prodrome Postdrome Mild F F F F F F F Post-Headache Aura Moderate Severe Rescue Onset - gradual (30-120 minutes) Location - 60% one sided; 40% bilateral Duration - 4 to 72 hours Quality - 85% throbbing Associated - 90% nausea; 35 % have vomited Aversion - light, sounds, smells Aggravated - by movement or exertion
Phase IV Late - Resolution Pre-Headache Prodrome Headache Post-Headache Aura Postdrome Mild Moderate Severe Rescue Headache pain improves Sometimes abruptly triggered by emesis or sudden emotionally intense experience Associated symptoms may resolve with or after headache resolution
Phase V Postdrome Headache Pre-Headache Prodrome Postdrome Mild F Post-Headache Aura Moderate Severe Rescue Migraine Hangover F Fatigue, irritability F Limited food tolerance F Scalp tenderness
Some Characteristics of Migraines Familial in 70% Prodrome Visual or neurological in classical Vague in common Migraine forerunners Motor sickness Cyclic vomiting in childhood
Episodic Migraine Sufferer Severe Impairment Moderate Impairment Mild Impairment Normal Neurological Function
Episodic Chronic Episodic Migraine Migraine Chronic Headache Headache Transformed Migraine Severe Impairment Sufferer Depression Depression Moderate Impairment Anxiety Anxiety Mild Impairment Normal Neurological Function Sleep Sleep Disorder Disorder
Risk Factors for Transformation Frequency Disability Comorbidity Obesity Sleep Disorders Lower Socioeconomic Status Head/Neck Trauma Stress Medications overuse
Chronic Daily Headaches Rare disorder Only 5 percent of the U.S. population suffer from severe headaches on a daily basis 3 percent meet criteria for chronic tension-type headaches Account for majority of consultations seen in headache subspecialty practices
Chronic Daily Headache Classification Difficult to classify under current IHS guidelines Alternative classification separated chronic daily headache into primary and secondary types Primary chronic daily headache can be subclassified by average daily headache duration New system includes entities not recognized by IHS
Chronic Migraine Prior history of episodic migraine starting during adolescence or twenties Female predominance As headache frequency increases, typical migrainous features become less frequent and severe Many migraine features persist Superimposed full-blown migraines
Chronic Migraines In the general population 30-50 percent of patients overuse medications Headaches increase in frequency with increasing medication use Headache improvement correlated with discontinuing analgesics Significant long-term improvement seen following detoxification
Transformed Migraines Eighty percent are depressed; improves as medication overuse discontinued Transformed Migraine not recognized by IHS Silberstein et al recently proposed criteria Prior IHS migraine criteria Period of escalating headache frequency with decreasing migraine
Analgesic Rebound Ergot Triptan Isometheptene Short-acting NSAID OTC Carispiridol Decongestants Caffeine Opioid Butalbital Anything
The Barrage of OTCs
Diagnosis of Medication Overuse Headache Diagnosis and treatment take time1 Offending medications must be stopped and prophylactic medications started Diagnosis is confirmed in retrospect Patients typically overuse multiple medications simultaneously2 Mean tablets/day = 5.2 Most commonly overused medications Drugs. Butalbital combinations acetaminophen 1. Smith and Stoneman. 2004;64:2503-2514. 2. Bigal et(48%), al. Cephalalgia. 2004;24:483-490. (46%), opioids (33%), ASA (32%), triptans (18%)
Recognition of Medication Headache Overuse HAs are refractory and frequent (near daily) Patient frequently uses excessive quantities of analgesics; tolerance may develop HAs may vary in severity, location, and type HAs are easily triggered by slight physical or mental effort Weakness, nausea, anxiety, irritability, and cognitive problems often accompany HA HA spontaneously improves when Diener and Katsarava. Curr Med Res Opin. 2001;17(suppl 1):S17-S21. offending medications are discontinued
Strategies for detox Clear discussion of outcomes Tapering schedules versus cold turkey Withdrawal medications Cycle breakers Bridge drugs Early prophylaxisis Frequent check-ins
Cycle Breakers Steroids Triptan bid Bellergal bid Long-acting nsaids DHE Anti-dopaminergics Occipital nerve blocks
Case Study 38 year old CEO with 3 kids comes in because she has 2 severe migraine per month for 15 years causing her to miss work and her kids events. Duration of headaches is 48 hours and often awakens her from sleep. Has more than 15 days of headache per month
Intensity Headache Experts Agree that the Optimal Treatment Strategy is to Treat Early, Before Central Sensitization Occurs Phases of a Migraine Attack Pre-HA Premonitory/ Prodrome Headache Aura Mild Moderate to Severe HA Post-HA Postdrome Time Adapted from Cady RK. Clin Cornerstone. 1999;1(6):21-32.
Migraine specific Two Main Approaches Triptans Non-specific analgesics DHE NSAIDs ASA/acetaminophen/caff eine Be aware Opiates No evidence to support use of butalbital compounds in migraine management Little evidence to support use of isometheptene compounds in migraine management Snow V, et al. Ann Intern Med. 2002;137:840-849.
Drug Therapy of Migraine Abortive Treatment - A Triptans Sumatriptan Parenteral Oral Intranasal Naratriptan Oral Almotriptan -oral Zolmitriptan -dissolvable disc Oral Rizatriptan Oral Dissolvable discs Frovatriptan Eletriptan
Time Is Critical in Harvard Research Suggests: From Preventing Migraine A Sequence of Events Leads to Central Becoming Full-blown Sensitization Meningeal blood vessel Thalamus Peripheral neuron (trigeminal ganglion) Pain pathways Central neuron (dorsal horn) Within minutes of a migraine being triggered, the peripheral neurons that innervate meningeal blood vessels become sensitized Burstein R et al. Ann Neurol. 2000;47:614-624. Burstein R et al. Brain. 2000;123:1703-1709. If migraine is left untreated, those peripheral pain neurons activate and sensitize central neurons, leading to central sensitization Central sensitization signifies full-blown migraine, when central neurons are continually firing and the attack becomes more difficult to treat
Tips on Triptans Don t do a grab bag Try one drug for 3 to 4 migraines with early intervention and at the right dose Talk about nausea and use appropriate formulation Dose selection Insurance limitations Don t give up if one doesn t work They aren t diagnostic tools They are equally safe They are a single class of drug
Phases of a Migraine Pre-HA Headache Post-HA Attack Mild Premonitory/ Prodrome Aura Moderate to Severe Headache Time Early Intervention Postdrome
Clinical Efficacy Parameters Pain-free Pain response 3 Severe 2 Moderate 1 Mild 0 No pain Sustained response No pain at 2 hours No recurrence (2-24 hours) No rescue medication (2-24 hours) Tfelt-- Hansen P, et al. Cephalalgia. 2000;20:765 Tfelt 2000;20:765--786.
Formulation Options Nasal Spray Rectal Injection
Nasal Spray Choices Agent Triptan* sumatriptan zolmitriptan D.H.E.* dihydroergotamine Pros Cons More rapid onset than tablets, one spray Same efficacy as tablets, not as convenient as triptan tablet Triptan Device assembly, 4 alternative sprays, efficacy less than triptan sprays, pregnancy category X Butorphanol Moderate Significant abuse efficacy * = migraine specific Clinical Role potential use with caution Alternate primary therapy, possible pediatric use Alternative for triptan nonresponders Cardiovascular risk patients, rescue if used infrequently = Non-specific narcotic analgesic
Rectal Choices Agent Ergotaminecaffeine* Antiemetics promethazine Prochlorperazine trimethobenzamide Pros Most reliable ergot route Cons Nausea and other ergot side effects, potential for ergotism pregnancy category X Stops Potential for nausea, antidopamine side may help effects, sedation migraine Indomethacin Nonnarcotic * = migraine specific Not commercially prepared, requires compounding = Non-specific analgesic Clinical Role Alternative for triptan nonresponders Managing nausea, add on to migraine specific medicine Cardiovascular risk patients, rescue alternative
Home Injection Therapy Sumatriptan injection/dhe-45 Pros Highest efficacy route Highly efficacious early or late in attack Cons Needle-phobia Requires patient instruction More side effects than tablet
Wake Up, Crash Migraine! Injection as Early Injection Intervention Injection Migraine Evolution 2004 PCN
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Structured treatment plan follow the program! Step 2: Behavioral Management Regular exercise Consider Biofeedback Regulate Sleep Caffeine taper to 2 a day or less Fluids maintain hydration Don t skip meals! Especially breakfast
Migraine Treatment 90 80 70 60 50 40 30 20 10 0 5 5. 5 4. 5 3. 5 2. 1. 0. 5 APAP/ASA/CAF* (n=602) Placebo (n=618) 5 Response (%) Effect of Combined Acetaminophen-Aspirin-Caffeine on Migraine Pain Hours *Significantly different from placebo; P# 0.001. At 0.5 hours, APAP/ASA/CAF significantly different from placebo; P# 0.05. Lipton RB et al. Arch Neurol. 1999; 55:210217
Dr. Enuf Contains (10 oz. Bottle): Caffeine: 68 mg Niacin: 0.006 mg
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Migraine Treatment Rescue Treatment for Moderate-to-Severe Migraine First-Line Migraine Continues Migraine Resolves Recurs Rescue Rescue Repeat First-Line Diamond S. Headache Q. 1998; 8:39-44 Hoffert MJ et al. Headache. 1995; 17:65-69 Consensus Opinion. Stadol NS C-IV (butorphanol tartrate) Advisory Board Meeting, April 12, 1997, Boston, Mass.
When do I use narcotics? When abortive treatment fails When it is not abused When abortive treatment is contraindicated pregnancy breastfeeding medical reasons/elderly allergy Appropriate for rescue Use long-acting agents/appropriate dosing
Guidelines to migraine treatment Two days of treatment per week ( of anything) Watch for escalation of dose and frequency Avoid addictive substances in patients at risk Watch for catch phrases and doses
Pharmacologic Treatment of Migraine Preventive vs. Acute Medication Preventive medication given daily to decrease migraine: Frequency Severity Duration Acute care medication given during an attack to: Decrease severity and duration Treat associated migraine symptoms (nausea, photophobia, sonophobia and vomiting)
Methods (cont d) The self-administered survey included questions on: Headache symptoms/features (to classify cases) Headache-related impairment (none, some, severe, or bed rest required) Migraine Disability Assessment (MIDAS) Headache frequency Headache frequency data were collected 2 ways: A. About how often do your severe headaches occur? # in a week OR # in a month OR # in a year B. On how many days in the last 3 months did you have a headache? (From MIDAS) Prevention # of daysneed was Prevention need was estimated estimated using using both both approaches, approaches, data data for for the the more more conservative conservative approach approach B B are are presented presented here. here. Lipton RB. Headache. 2005;65:792. Abstract F38.
Prevention Need The decision to use preventive treatment should be based on doctor-patient collaboration as well as: Headache frequency Headache-related impairment In this study self-reported past 3-month headache frequency data were obtained (via MIDAS) and standardized to an average month Expert consensus Lipton RB. Headache. 2005;65:792. Abstract F38. was used to classify individuals
Preventive Rx Need Among Migraine Cases (Past 3-Month Frequency Based on MIDAS) Monthly Migraine Days How are you usually affected by severe headaches? ( # of Days in Last 3 Months) 1 2 3 Able to Work/ Function Normally 4.4% 0.6% 0.7% Impaired to Some Degree 22.6% 3.5% Severe Impairment Bed Rest Required 33.0% 4.6% Total 60.0% 4-5 6-10 11+ Total 0.6% 0.5% 0.4% 7.2% 4.4% 3.5% 3.1% 2.0% 39.2% 5.2% 4.1% 3.9% 2.9% 53.7% 8.7% 10.3% 8.2% 7.5% Offer Preventive Treatment = 25.7% Consider Preventive Treatment = 13.1% Not Indicated = 61.3% Lipton RB. Headache. 2005;65:792. Abstract F38. 5.3% 100% n = 18,670
Pharmacologic Treatment of Migraine Preventive vs. Acute Medication Preventive medication given daily to decrease migraine: Frequency Severity Duration Acute care medication given during an attack to: Decrease severity and duration Treat associated migraine symptoms (nausea, photophobia, sonophobia and vomiting)
Consider Migraine Preventive Medication When The Patient Has: 1. Recurring migraine that the patient feels significantly interferes with his or her daily routine 2. Two or more attacks per month that produce disability lasting three or more days per month 3. Overuse of acute medications (>2 week) 4. Acute medications are ineffective, contraindicated, or not well tolerated 5. An uncommon migraine condition: Hemiplegic Migraine Migraine with Prolonged Aura 6. Patient preference Migrainous Infarction Basilar Migraine Silberstein SD et al. Headache. 2003;43:171; Snow et al. Annals of Internal Medicine. 2002;137:846.
How to Choose Therapy Evidence-based Sleep disorders Related to comorbid condition depression anxiety /panic epilepsy
Using Preventive Start Medications with low dose and increase slowly Allow time for an adequate trial (2 to 6 months) Avoid drug overuse and interfering drugs Evaluate therapy Use a headache calendar Taper (and stop?) if headaches well controlled No established guideline on this clinical practice generally runs from 6 to 18 months of well-controlled migraines Discuss pregnancy issues before initiating therapy
Migraine Prophylaxis FDA Approved Drugs Methysergide (Sansert) Propranolol (Inderal; Inderal LA) Timolol (Blocadren) Divalproex Sodium (Depakote) Topiramate (Topamax)
Antidepressants NSAIDs 5-HT antagonists Preventive Medications TCAs, SSRIs, MAOIs Amitriptyline, nortriptyline Cardiovascular medications Propranolol Timolol Verapamil Antiepileptic drugs (AEDs) Divalproex Gabapentin Topiramate Other Methysergide* Other Riboflavin (B2) Feverfew Magnesium (Mg++) Botulinum toxin Petasites ACE inhibitor Angiotensin II antagonist Coenzyme Q TCAs=tricyclic antidepressants; SSRIs=selective serotonin reuptake inhibitors; MAOIs=monoamine oxidase inhibitors; NSAIDs=nonsteroidal anti-inflammatory drugs; ACE=angiotensin-converting enzyme. Currently indicated for migraine prophylaxis by the FDA *Not available in the United States.
Potential Mechanisms of Glutamate GABA Migraine Preventives Neurotransmissi Neurotransmissi NE 5-HT on on β-blockers â - âââ - Tricyclic Antidepressants â á á ááá ââ - - - âââ ááá Gabapentin - ááá - - Topiramate âââ ááá - - Ca Channel blockers Valproate GABA=gamma-aminobutyric acid; NE=norepinephrine; Adapted from Silberstein SD et al. Wolff s Headache and Other Head Pain. 2001:121-237.
Prevention Reduces Costs Using both acute and preventive therapies results in: Office visits 51% Emergency department visits 82% CT scans 75% MRI scans 88% Acute medication costs $48 to $132/month/patient based upon sumatriptan use (2001 $) Silberstein SD et al. Headache. 2003;43:171-178.
Patient Diaries How medication is used When medication is used Triggers Efficacy of medication Duration of the headache Patient ownership
Beta Blockers Propranolol LA 60mg-240mg Nadolol 20=120mg Metoprolol 50mg-200mg Timolol 10-20mg side effectshypotension,lethargy,depression
Antiepileptics Divalproex 125-2000mg Gabapentin 200-3000mg Topirimate 25-250mg side effects- weight,cognitive,hair loss,tremor,paresthesias
Antidepressants Tricyclics SSRI Atypical antipsychotics MAOI
Drug Effects of Antidepressants - 1Serotonin Nor- Dopamin Sedative AntiInhibition Amitriptyline Moderate Epinephrine e Inhibition Inhibition Effects Cholinergi c Effects Weak Inactive Strong Strong Doxepin Moderate Moderate Inactive Strong Strong Nortriptyline Weak Fairly potent Inactive Mild Moderate Imipramine Fairly potent Moderate Inactive Moderate Strong
Effects of Antidepressants - 2 Serotoni Nor- Dopamin Sedative Anti- Drug n Epinephrine e Inhibition Inhibition Inhibition Effects Cholinergi c Effects Protriptyline Weak Fairly potent Inactive None Strong Desipramine Weak Potent Inactive Mild Moderate Trimipramine Weak Weak Inactive Moderate Moderate Amoxapine Weak Potent Moderate Mild Mild Maprotiline Weak Moderate Inactive Moderate Moderate
Triptans: Use with SSRIs 50 n=94,522 % Prescriptions 40 28 30 20 18 10 0 Males Females Source: Pharmacy Claims Database
Effects of Antidepressants - 3Serotoni Nor- Dopamin Sedative Anti- Drug n Epinephrine e Inhibition Inhibition Inhibition Effects Cholinergi c Effects Trazadone Fairly potent Weak Inactive Strong Mild Fluoxetine Potent Weak Inactive None Mild-None Buproprion HCl Weak Weak Weak None None Sertraline HCl Potent Weak Weak None None Paroxetine HCl Potent Weak Weak None None
Effects of Antidepressants - 4 Serotoni Nor- Dopamin Sedativ AntiDrug n Epinephrine e Inhibition Inhibition Inhibition e Effects Cholinergi c Effects Vanlaxafine Potent Potent None None Mild Fluvoxamine (Luvox ) Potent Inactive Inactive Mild Mild Clomipramin e (Anafranil ) Potent Inactive Inactive Mild Mild Mirtazapine (Remeron ) Potent Inactive Inactive Promine nt None
Calcium Channel Blockers Verapamil 180-360mg Diltiazam 180-360mg Side effects- constipation,dyspepsia
Miscellaneous Cyproheptadine-2-16mg NSAID Occipital nerve block Tizanidine 2-24mg Botulinum toxin