Migraine: Clinical Overview, Medication Overuse and Treatment Options Esther Tomkins Clinical Nurse Specialist

Institutions & Organisations National organizations – Migraine Association of Ireland (MAI) & Migraine Trust (UK) European Headache Federation (EHF) World Health Organization (WHO) European Brain Council Lifting The Burden (LTB) Focus on the high prevalence and high disability of headache

Clinical Burden of Headache Tension-type headache and migraine are the second and third most prevalent medical disorders on the planet Account for 4% of consultations in primary care in the UK1 GP’s refer 2% to neurology clinics Accounts for 30% neurology outpatient consultations in the UK1 Migraine is the most common primary headache seen by doctors (population prevalence of 15%)1 Affects over 500,000 people in Ireland2 Cause severe disability in some patients3 NICE Clinical Guideline 150. Headaches costing report. September 2012 The Irish Nurses & Midwives Organisation http://www.inmo.ie/Home/Index/7066/8626 Accessed OCTOBER 2013 World Health Organization. The Global Burden of Disease: 2004 update, Part 3, p28–37. http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/ last accessed October 2013

Burden of Migraine World Health Organisation (WHO) – in 2000, migraine ranked as the 12th most disabling medical condition for women WHO (Global Burden of Disease study, 2010) - migraine ranked as the 4th most disabling medical condition for women (7th most disabling overall)2 Chronic Daily Headache >15 days per month (affects 3-4% of people in the UK)3 In lower socioeconomic populations, higher prevalence of CDH (for example, 10% Russia & 8% Georgia) WHO (2001) The World Health Report 2001: Mental health, new understanding new hope. World Health Organization, Geneva, Switzerland www.who.int/whr/2001/en/whr01_en.pdf Accessed October 2013 World Health Organization and Lifting The Burden. Atlas of headache disorders and resources in the world 2011. WHO, Geneva; 2011. NHS UK http://www.nhs.uk/Livewell/Pain/Pages/Headachesandmigraines.aspx Accessed October 2013

Burden of Migraine Estimated migraine costs Direct costs – medication, out patient visits, healthcare1-2 Indirect costs - work, productivity, impaired quality of life, financial burden1-2 Annual cost per patient - €1,200/year (plus medication overuse €3,500/year) Migraine - in the EU, migraine is estimated to cost €50,000,000,000 per annum (plus 37 billion per annum for medication overuse headache) 1. Steiner TJ et al. Cephalalgia 2003;23:519–527. 2. Hawkins K et al. Headache 2008;48:553−563.

Lancet 2012; 380: 2197–223 Tension-type headache and migraine are the 2nd and 3rd most prevalent medical disorders on the planet Migraine accounts for 30% of the global burden and more than 50% of the disability burden attributable to all neurological disease worldwide. Overall, it is the 4th ranking cause among women and the 7th ranking cause of all disease-associated disability worldwide.

How to Classify Headache Migraine (episodic V chronic) Tension-type Headache (TTH) Trigeminal Autonomic Cephalgias (TAC) – Cluster Headache, Hemicrania (Paroxysmal & Hemicrania Continua), SUNA/SUNCT Secondary Headache – bleed, stroke, infection (meningitis), tumours, CSF pressure (low/high), seizure related Cranial neuralgias (trigeminal neuralgia) Central causes of facial pain (neuropathic facial pain)

Migraine Neurological Condition - brain disorder Complex syndrome - not just Headache Headache with associated features Dysfunction of nerve cells in the brain Causes brain hypersensitivity Genetic factors - family history Three genes for familial hemiplegic migraine (FHM) are known

Migraine – How common? Very common Prevalence 4/10 Women, 2/10 Men 90% patients attending GP with headache were diagnosed with Migraine (Tepper et al., 2004) Patients are often diagnosed with tension-type headache, neck problems or sinusitis

Migraine – Diagnostic Criteria Classification (2004) Repeated attacks lasting 4-72 hours: - Normal physical examination - No other reasonable cause for the H/A - At least 2 of: pain on one side, throbbing/pounding pain, movement aggravation, moderate/severe intensity - Nausea, vomiting, photophobia or phonophobia

Migraine – Human Cost Patients – 25% will have four or more severe attacks per month (lasting 24 hours) Episodic migraine often changes into a chronic daily headache (CDH – defined as headache on more than 15 days per month – often daily) The headache is usually mild for most of that time – superimposed severe episodes Transformed migraine or chronic migraine

Most Important Clinical Points Patients history – all important Aim is to get a definite diagnosis and exclude secondary causes of headache Inadequate history is the cause of most misdiagnosis Most headache groups have developed standard questions to help with history taking (for example, the Headache Information Board in Beaumont)

Tools to Aid the Clinical History Almost all headache experts use headache diaries and appropriate assessment questionnaires to diagnose and manage headache Headache Impact Test (HIT/HIT6) & Migraine Disability Assessment (MIDAS) ID Migraine

Migraine – Patients Symptoms Headache – pounding, tight, pressure, dull ache, muzziness, fullness or abnormal sensation Headache may not be a prominent feature Location: top, front or back of head – not always one sided Photophobia, Phonophobia & Osmophobia Nausea/Vomiting – travel sickness, repeated abdominal pain Unsteadiness/dysequilibrium – like being on a boat or drinking alcohol (without the alcohol)

Migraine – Symptoms Eyes – drooping eyelids, swelling around eyes, tearing or conjunctival injection (bloodshot) Visual – wavy lines, visual loss of part of vision (eg. tunnel vision) Nose – stuffed (nasal congestion) in 87% of people with migraine - confused with sinusitis Face – neuropathic facial pain: pain in teeth, jaw, cheeks, TMJ Limbs – pain, tingling, numbness, “heaviness”, weak (hemiplegic migraine) Ears – pain, fullness, deafness or tinnitus Neck/back – stiff neck, shoulder & back pain

Symptoms - Summary Migraine patients often have a variety or constellation of different symptoms affecting head, vision, balance, neck, ears, nose, eyes, scalp, face & limbs Headache may NOT be the most prominent symptom Often labelled as depressed, tension type headaches, neck related headaches, jaw/teeth problems or sinusitis

Migraine – Triggers Change in routine Stress Hormonal changes Alcohol Sleep habits – sleeping in, sleep deprivation Eating habits – going hungry (low sugar levels) Stress Hormonal changes Alcohol Weather – stormy weather Food and drinks

Migraine – Hormonal Factors 70-80% of our patients are female Migraine usually worse from teens to 50’s Often worse perimenstrually Migraine with aura, smoking and COCP not good combination – higher risk of stroke Hormone manipulation of limited benefit Mirena and progesterone only pill (POP)

COMMON TRIGGERS (Kelman 2007)

Primary Headache Disorders: Frequency Classification1,2 After Secondary Causes Are Ruled Out Silberstein Neurol 1996, p872 Dodick NEJM 2006, p158, 159/Table 1 Primary Headache Disorders Chronic Headache Frequency ≥15 days/month Episodic Headache Frequency <15 days/month 1 / Silberstein Neurol 1996, p872, 873 2 / Dodick NEJM 2006, p159/Table 1, 160/Table 2 p158 3 /Scher 1998 p498, 500 4/Castillo 1999 p 192 5/Lanteri-Minet 2003, p145 Primary chronic daily headache (CDH) of long duration is a syndrome characterized by headaches not attributable to a secondary disorder that last more than 4 hours a day and occur 15 or more days per month.1,2 This syndrome affects 3-5% of the general population worldwide2-5 and approximately 40% of patients seen in headache clinics.6 The criteria most frequently used to classify primary chronic daily headache of long duration are those proposed by Silberstein and Lipton.1 According to these criteria, the chronic daily headache syndrome encompasses 4 main diagnoses1,2: Chronic Migraine Chronic tension-type headache New daily persistent headache Hemicrania continua These subgroups are further divided into those with and without medication overuse.1 References: Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: field trial of revised IHS criteria. Neurology. 1996;47:871-875. Dodick D. Chronic daily headache. N Engl J Med. 2006;354:158-165. Scher AI, Stewart WF, Liberman J, Lipton RB. Prevalence of frequent headache in a population sample. Headache. 1998;38:497-506. Castillo J, Munoz P, Guitera V, Pascual JG. Epidemiology of chronic daily headache in the general population. Headache. 1999;39:190-196. Lanteri-Minet M, Auray J-P, El Hasnaoui A, et al. Prevalence and description of chronic daily headache in the general population in France. Pain. 2003;102:143-149. Mathew N, Reuveni U, Perez F. Transformed or evolutive migraine. Headache. 1987;27:102-106. Short-Duration Chronic Daily Headache Duration <4 hours or multiple discrete episodes Chronic Daily Headache (Long Duration) Daily or near-daily headache lasting ≥4 hours With or Without Medication Overuse 1 / Silberstein Neurol 1996, p872 1. Silberstein SD et al. Neurology. 1996;47:871-875. 2. Dodick D. N Engl J Med. 2006;354:158-165. 6 / Mathew 1987, p103 table 1

Differential Diagnosis of Chronic Daily Headache New Daily Persistent Headache1,2 Includes at least 2 of the following characteristics: Defined by new onset (within 3 days) and persistency Bilateral location Pressing/tightening (non- pulsating) quality Mild or moderate intensity Not aggravated by routine physical activity such as walking or climbing stairs Chronic Migraine1,2 Unilateral location Pulsating quality Moderate/severe pain intensity Aggravated by routine physical activity 1 / ICHD-2 - HCC; Olesen 2004, p52 2 / Dodick NEJM 2006, p160/Table 2 1 / ICHD-2 - HCC; Olesen 2004, p52 2 / Dodick NEJM 2006, p160/Table 2 1 / ICHD-2 - HCC; Olesen 2004, p39 2 / Dodick NEJM 2006, p160/Table 2 1 / ICHD-2 - HCC; Olesen 2004, p24-25, 31-32 2 / Dodick NEJM 2006, p159 Hemicrania Continua1,2 Includes all of the following characteristics Strictly unilateral location Daily and continuous, without pain-free periods Moderate intensity, but with exacerbations of severe pain Indomethacin-responsive This slide summarizes the differential diagnosis of the types of chronic daily headache: Chronic Migraine, new daily persistent headache, hemicrania continua, and chronic tension-type headache.1,2 References: 1. Headache Classification Committee; Olesen J, Bousser MG, Diener HC, et al. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24(suppl 1):9-160. 2. Dodick D. Clinical practice: chronic daily headache. N Engl J Med. 2006;354:158-165. Chronic Tension-Type Headache1,2 Includes at least 2 of the following characteristics: Bilateral location Pressing/tightening (non- pulsating) quality Mild or moderate intensity Not aggravated by routine physical activity 1 / ICHD-2 - HCC Olesen 2004, p24-25, 31-32 2 / Dodick NEJM 2006, p159 1. Headache Classification Committee; Olesen J et al. Cephalalgia. 2004;24:9-160. 2. Dodick D. N Engl J Med. 2006;354:158-165.

Migraine, Medication Overuse & Chronic Daily Headache (CDH) Up to 80% of patients consulting in headache clinics suffer from CDH Medication overuse reflects an interplay between a therapeutic agent & the mechanism for headache Also called chronic migraine, transformed migraine and rebound headache

Principles of Acute Treatment Painkillers/analgesics, triptans and NSAID’s are excellent drugs if used infrequently or for short courses Number of days per month is the key Regular use of even small doses (more than one/two days per week) is a bad idea Avoid codeine and opiates Naproxen (Naprosyn) more frequently

Treatment Options for Migraine Reduce acute medications as much as possible (analgesics/painkillers, non-steroidal anti-inflammatory agents & triptans) – keep diary! Preventative agents if needed (>8/30) Greater occipital nerve (GON) blocks Botox (PREEMPT protocol) In-patient treatments (IV DHE, lidocaine, etc,) Neuromodulation

Preventative Medication Every day for at least 4-6 months at a reasonable dose – all have potential side effects Different classes of preventatives Flunarizine/Sibelium - can take many months Tricyclics - Amitriptyline, Nortriptyline BP medication - Propranolol (Candesartan) Epilepsy medication - topiramate, valproate, gabapentin (zonisamide) Pizotifen (Sanomigran) Pregabalin (Lyrica)

Amitriptyline (TCA) Commonest prescribed migraine agent It is an “old” anti-depressant Maximium dose of 300mg For migraine, use 10-150mg Start at 10mg at night for 2-8 weeks Possible common side effects (dreams, drowsiness, dry mouth, weight) Use for 4-6 months at maximium tolerated dose before considering changing

Topiramate/Topamax In the top three most commonly prescribed migraine agents It is also an epilepsy medication Highest daily dose of 700mg For migraine, use 25mg to 200mg twice daily Start at 25mg at night for 2-8 weeks and increase gradually Common side effects of weight loss, tingling, mood, speech, kidney stones Use for 4-6 months at highest tolerated dose before considering changing

Flunarizine/Sibelium In the top three most commonly prescribed migraine agents Highest dose of 15mg daily Start at 5mg once daily for at least 3 months (often longer) Common side effects of weight gain, mood disturbance or anxiety Use for 4-6 months at highest tolerated dose before considering changing

Gabapentin (Neurontin) Second line migraine drug Also used in epilepsy & pain management Maximium dose of 4800mg daily Start at 100mg BD for 1-2/52: aim for 300mg TDS as a starting maintenance dose (may need much higher doses) Possible common side effects (weight gain, abdominal symptoms) Use for 6/12 at maximium tolerated dose before considering changing

Valproate (Epilim) Second line migraine drug Also used in epilepsy & psychiatry Maximium dose of 3000mg daily Start at 200mg OD for 1-2/52: aim for 400mg – 600mg as a maintenance dose (may need higher doses) Possible common side effects (weight gain, abdominal symptoms) May act as a mood stabiliser Not good for women of child bearing age Use for 6/12 at maximium tolerated dose before considering changing

GON Blocks Greater occipital nerve (GON) blocks Often used to supplement one or two migraine preventative agents Migraine patients with at least 15-20 headache days per month Also used in other primary headaches (Cluster) No more than three blocks each side per year Very little side effects Suitable for pregnant/breast feeding patients May need several blocks for prolonged benefit

Botox Based on the two PREEMPT studies 31-39 injections (5 units each) per patient Migraine patients with at least 15-20 headache days per month Often used in combination with preventative agents Every three months Very little side effects Suitable for patients considering children May need several courses of injections

Beaumont & Mater Hospital Headache Clinics Multidisciplinary (doctors, nurses, PT, etc.) 45-60 patients per week Vast majority of patients have migraine >50% of patients have chronic daily headache (CDH)

Conclusions Migraine is very common & can be very disabling Migraine can give a variety of different symptoms (headache may not be that prominent) Affects more women than men Frequent regular use of acute medications is not good in patients with migraine