2015-11-01

1

Christine Lay, MD, FAHS Associate Professor of Medicine (Neurology)

Director, Centre For Headache

Women’s College Hospital

High Frequency and Chronic Migraine: Current and Future Management Strategies

Disclosure

! This lecture has not been financially compensated ! This lecture will reference both on and off-label uses of

medications in the treatment of migraine and this will be identified wherever possible.

! Potential for conflict(s) of interest: ■  The Centre for Headache (CL and/or SL) have received grant/

research support/funding from Allergan, Tribute and Teva whose respective products onoabotulinum toxin, diclofenac potassium and frovatriptan will be discussed in this program

2015-11-01

2

Learning Objectives

●  Identify high frequency and chronic migraine patients ●  Utilize pharmacological and non-pharmacological

treatment strategies for therapy ●  Become aware of up and coming new therapies

Steps For Treatment Success

1. Diagnose 2. Assess Disability 3. Educate 4. Individualize Care 5. Stratify Therapy

2015-11-01

3

Dowson A, et al. Cephalalgia 2002;22:590-591.

Headache Sufferers vs Those Seeking Care

Sufferers seeking care General Population

Migraine

16% 76%

Tension-type Headache

78%

3% Migrainous

Other 3%

Other 6%

18%

Rasmussen et al., J Cin Epidemiol 1991;44:1147-1157.

Migraine ●  is a complex neurological disorder ●  not just a headache - it affects multiple sites

■  cortical (photophobia, phonophobia etc), ■  subcortical (fatigue, euphoria, yawning, cravings) ■  brainstem (muscle neck pain)

●  as a result, sensory, affective, autonomic and cognitive functions are compromised

●  often a few times/yr in childhood and progresses over time to few times/week with time

2015-11-01

4

How Does Migraine Impact Patients?

American Migraine Prevalence and Prevention study results (Lipton RB et al. Neurology. 2007;68:343-349).

7.2

39.153.7

Function Normally

Some Impairment

Severe Impairment orBed Rest Required

Headache-Related Impairment During a Severe Attack

Lost Years to Disability: Neurological Disorders

Vos, Lancet 2012.

Migraine Dementia Parkinsons Epilepsy Atherosclerosis Headache Others Stroke

2015-11-01

5

What are the 3 best clinical clues to diagnose migraine?

1.  Unilateral, throbbing, nausea 2.  Throbbing, photophobia, worse with

activity 3.  Impairing, photophobia, nausea 4.  Unilateral, more than 4 hours,

osmophobia

Survey says…

ID MIGRAINE: Simple, Accurate, Fast Screener

●  Strongest predictors of migraine diagnosis ■  Photophobia

–  Does light bother you when you have a headache? ■  Impairment (Disability)

–  Has a headache limited your activities for a day or more in the last 3 months?

■  Nausea –  Are you nauseated or sick to your stomach when you

have a headache? ●  2 out of 3 symptoms: 93% PPV, 81% Sensitivity, 75%

Specificity ●  3 out of 3 symptoms: 98% PPV

Lipton RB, Dodick DW, et al. Neurology. 2003;61:375-382.

PIN the diagnosis

2015-11-01

6

Risk Factors EM èHFMè CM Bigal 2008, Blumenfeld 2011, Katsarava 2012

●  Prevalence CM 0.9% in normal wt , 2.5% in ++ obese ●  Caffeine in diet, Rx and non-Rx meds

■  CM more likely to be high consumers while had EM ■  Starbuck’s Grande = 9 cans coke (330mg vs 32mg)

●  May be a biologic predisposition ■  Prevalence of CM is elevated in 1st degree relatives

●  Frequency may be a cause or a consequence ●  Medication use/overuse – édoses with ê effect

■  Barbiturates/opiates OR 1.25 at 5d/month ■  Triptans – don’t increase risk of CM (OR 1.07) but associated with

progression to CM at days >10-14/mo ■  NSAIDs – protect/promote – ibuprofen>2 days/week è MOH

Risk Factors for MOH

●  Smoking – 2x increase ●  Inactivity – 2x increase ●  Alcohol consumption ●  Tranquilizer use ●  Comorbid anxiety/depression ●  Family Hx MOH or substance abuse ●  70% MOH pts fulfill DSM-IV or severity of

dependence scale for substance abuse Lundqvist 2010, Zwart, Neurology 2004, Jonsson, Cephal 2011, Cephalalgia 2010, 2012

2015-11-01

7

Risk Factors AM è HFMè CM Scher AI, et al. Pain. 2003

●  Snoring, sleep disorders (insomnia), disturbed sleep maintenance……70% prevalence ■  consider sleep study, check iron, ask about ETOH ■  Mindfulness

●  ACE – Adverse Childhood Experience

HA and ACE §  Increased risk of chronic HA in adults who experienced

childhood maltreatment ACE §  Physical abuse, sexual abuse, emotional abuse, parental discord,

alcoholic parent §  Screen for depression/anxiety/abuse ●  Stress affects immunity and inflammation ●  Adults with ACE have increased inflammatory markers ●  Different gene expression in brains of ACE ●  Abnormal cortisol regulation – increased cortisol levels with

minimal stress, suppressed immunity, memory impacted Danese, Fugundes, S

2015-11-01

8

Migraine progression

o  Transformation is often gradual and can evolve over several months or years

o  Transformation is neither inexorable nor irreversible

■  Spontaneous or induced remissions are possible and common

No migraine

Low-frequency episodic migraine (4-6/mo)

High-frequency episodic migraine (6-14/mo)

Chronic Migraine

(>15 d/mo)

Lipton RB. Neurology. 2009;72:S3–S7.; Bigal ME, Lipto RB. Curr Opin Neurology. 2008;21:301–308. Manack A et al. Neurology. 2011;76:711–718.

Epidemiology of Chronic Migraine

Prevalence of Chronic Migraine: 1.4%–2.2% in general practice1

80% of CDH in headache clinics

Chronic Migraine with or without medication overuse2

Chronic daily headache accounts for 30%–80% of patients in

headache clinics2

1.  Natoli JL et al. Cephalalgia. 2010;30:599–609. 2.  Silberstein SD et al. Neurology. 1996;47:871–5.

2015-11-01

9

Importance of Chronic Migraine diagnosis

●  Almost 300,000 Canadians*, mostly women, suffer from Chronic Migraine1

●  Only approximately 20% of patients receive a Chronic Migraine diagnosis2†

*Estimated global Chronic Migraine prevalence rate of 1%1 has been applied to 2010 Canadian population figures for individuals 18 years of age and older (n=27,196,554) (Source: Statistics Canada).

†Based on US population data.2

1.  Natoli JL et al. Cephalalgia. 2010;30:599–609.

2.  Bigal ME et al. Neurology. 2008;71:559–566.

The ID-Chronic Migraine (ID-CM) Screening Tool

A 12 item screening tool developed by

Headache specialists to help identify CM not to diagnose CM

2015-11-01

10

Treatment ●  Education – get ‘head-ucated’ (L Newman) ●  Acute Meds/Preventative Meds ●  Vitamin/Herbal ●  Lifestyle Modification

■  Sleep routine – insomnia, maintenance, quality, naps ■  Hydration ■  Limit caffeine – Grande Starbucks = 9 cans coke ■  Reduce high fructose drinks ■  Eliminate additives/dyes – migraine triggers ■  Eating routine - especially breakfast/protein ■  Mindfulness, Relaxation

Formulating a treatment plan for your patient: clinical questions to consider

●  Is the attack easy to recognize from the start? ● Does pain build quickly or slowly? ● Does it come on during the day when it can be

treated early? ●  Is there significant nausea early? Is there vomiting? ● What are the functional repercussions of the

attack? Does it lead to bed rest, absenteeism? ● What is the frequency of attacks (risk of medication

overuse)?

2015-11-01

11

Acute Migraine Medications Specific/Approved Health Canada ●  Triptans ●  Dihydroergotamine ●  Diclofenac K for oral solution

(Cambia)

Nonspecific ■  NSAIDs ■  combination

analgesics ■  corticosteroids ■  Antiemetics No Opioids!!

Snow V et al. Ann Intern Med. 2002;137:840-852.

Canadian Guidelines Acute Rx Canadian Journal Neurol Sci 2013

Rx Early

2015-11-01

12

Rx Migraine Treatment Strategies After OTC Failure

Adapted from: Worthington et al. Can J Neurol Sci 2013;40:S1-S80

Increasing migraine severity – Refractoriness to therapy

Moderate–severe attack /

NSAID failure

Refractory migraine

Prescription NSAIDs

•  Voltaren •  Cambia •  Naproxen Sodium NSAID ± metoclopramide

NSAID w/ triptan rescue •  NSAID

± metoclopramide

•  Voltaren •  Cambia •  Aleve •  + A triptan later

for rescue if necessary

Triptan •  Triptan

± metoclopramide

Imitrex®(SC injection, nasal, oral) Zomig®, nasal, oral, wafer) Maxalt®(oral, wafer) Amerge® oral) Relpax®( oral) Axert®(oral) Frova®( oral)

Triptan + NSAID

Triptan + NSAID

(simultaneously) ±

metoclopramide

Triptan + NSAID w/ rescue • Triptan + NSAID (simultaneously) ± metoclopramide + ≥1 for rescue later (as nec.) of: •  Ketorolac •  Indomethacin •  Prochlorperazine •  Chlorpromazine

Dexamethasone or prednisone

Dihydroergotamine Dihydroergotamine (nasal, or SC, IM self inj.) ± metoclopramide

* Diclofenac potassium is now available as a novel water soluble buffered powder formulation (Cambia) with a Tmax of approximately 15 minutes. It has shown superiority over the regular tablet at the same dose for onset of action and the pain-free at two hours endpoint in clinical trials

Mild–moderate attack /

OTC failure

Treating Fast is Important:

Delayed Treatment Can Lead to Failure

Pryse-Phillips W, Aubé M, Bailey P et al. A Clinical Study of Migraine Evolution. Headache: The Journal of Head and Face Pain 2006;46(10):1480-6.

•  Severe pain can occur within 20-60 minutes in up to 75% of patients

•  After 60 minutes of onset, treatment success drops significantly from 80% to 50%

60 min.

Minimal

Severe

Delayed Treatment

PAIN

Failure

Treatment Initiation

Time

Worthington I, Pringsheim T, Gawel M, et al on behalf of the Canadian Headache Society Acute Migraine Treatment Guideline Development Group. Canadian Headache Society Guideline: Acute Drug Therapy for Migraine Headache. Can J Neurol Sci. 2013;40[suppl 3]:S1-S80.

Moderate

2015-11-01

13

Case ●  36 year old woman ●  menstrual headaches as a teen ●  now with more severe headaches 6x/month ●  headaches last 3 days, first day mild ●  18 days/month ●  bilateral, non-throbbing pain ●  associated neck pain, prefers dark/quiet ●  using Tylenol #1 (6/mo) and ibuprofen 600mg q4h (30/month) ●  Sleeps in on weekends

Where do we start?

Calendar

Sunday Monday Tuesday Wednesday Thursday Friday Saturday H H H H H H H H H H H H H H H H H H H

2015-11-01

14

Calendar

Sunday Monday Tuesday Wednesday Thursday Friday Saturday H H H H H H H H H H H H H H H H H H H

Case

●  Cycle regular, not on OCP ●  Treats on day 2 when pain escalates ●  Often on weekends, can be bedridden by day 3 ●  Blames it on stress of her job Diagnosis – 18 days/mo, debilitating HA with P/P

■  HFM/CM & MOH ■  Under-treating

●  Sleep routine, keep calendar, lifestyle ●  Mindfulness ●  Taper codeine, stop OTC ●  Treat early with powdered diclofenac +/-triptan ●  Preventative?

2015-11-01

15

CALENDAR

Case

●  Returns 3 months later: ■  Treating at mild migraine with NSAID +/- triptan ■  Getting excellent results ■  HA lasts 2-3 hours and not disabling ■  No need for preventative as with lifestyle changes, HA

reduced to 3/month ■  Sleep improved

2015-11-01

16

What if our case has…..

●  Returns 3 months later: ■  Treating at mild migraine with triptan ■  Getting better results but some HA lasts 1-2 days ■  Sleep still problematic ■  Calendar shows 12 days/month

■  Sleep Study ■  Preventative

Prevention ● Establish expectations of reduced, not

eliminated migraines ● Provide acute medicines with limits ● Headache diary ● Pick medications that will treat concomitant

conditions: get a pharmacologic two-4-one ● Need 2-3 month trial ● Patients are often non-compliant

2015-11-01

17

Preventative Agents ●  Start low, go slow - better efficacy at lower doses with fewer side effects

●  Approved Agents ■  onabotulinum toxin ■  topiramate ■  divalproex ■  timolol ■  propranolol

●  Off Label - numerous agents ■  nadolol, verapamil, flunarazine, candesarten ■  nortriptyline, amitriptyline ■  gabapentin ■  ssris

●  Herbal - magnesium, riboflavin, butterbur, co-enzyme Q-10, melatonin

CHS Guidelines Episodic Migraine Prevention

Can Jour Neuro Sci 2012 ●  Prophylactic drug choice should be based on evidence for

efficacy, side-effect profile, migraine clinical features, and co-existing disorders

●  11 strong recommendation for use (topiramate, propranolol,

nadolol, metoprolol, amitriptyline, gabapentin, candesartan, butterbur, riboflavin, coenzyme Q10, and magnesium citrate)

●  6 weak recommendation (divalproex sodium, flunarizine, pizotifen, venlafaxine, verapamil, and lisinopril)

●  Consider co-morbidities

2015-11-01

18

What if our case has…..

●  Returns 3 months later:

■  Cannot stop codeine – No realizes was using 10-12/month –  Treating at moderate migraine with triptan

■  HA lasts 1-2 days ■  Sleep still problematic ■  Calendar shows 16 days/month This is CM ■  Sleep Study ■  Preventative

Chronic Migraine Prevention

●  Only approved agent is onabotulinum toxin A ●  Based on PREEMPT protocol ●  Reserved typically for those who fail 2 agents ●  Now approved by most insurance companies and recently by

ODSP = must submit 3 month calendar data ●  New ‘tweak’ in protocol so ensure your patient is going to a

headache-trained injector

●  Consider co-morbidities

2015-11-01

19

Why Treatment Fails

●  Diagnosis is incomplete or incorrect ●  Important exacerbating factors have been missed ●  Pharmacotherapy has been inadequate:

■  Too high a dose was initiated, resulting in side effects ■  Too low a dose was reached to evaluate effectiveness ■  Too short a period for treatment (must be 2-3 mos)

●  Nonpharmacologic treatment has been inadequate ●  Other factors, including unrealistic expectations and

comorbidity ●  Patient is in MOH; frequent use of acute meds nullifies

effectiveness of prophylaxis

Lipton et al. Neurology 2003;60:1064-1070.

What’s New for HFM/CM?

●  Patch, needle-free sumatriptan and sumatriptan with naproxen (Treximet) ●  Inhaled DHE

●  Monoclonal antibodies targeting CGRP – RCTs phase III ■  CGRP intimately involved in every stage of migraine ■  CGRP levels are increased during a migraine attack ■  Following resolution of migraine, CGRP levels normalize ■  Statistically significant reduction migraine attacks in phase II

●  Cefaly - TENS unit – approved ●  GammaCore - External vagal stimulator –approved

●  rTMS – repetitive transmagnetic stimulation – studies underway ■  Reduces cortical excitability, decreases/stops CSD

●  Cerena – at home, single pulse TMS device for migraine w/aura

2015-11-01

20