MANAGING MANAGING PRIMARY PRIMARY

HEADACHESHEADACHESAN OVERVIEWAN OVERVIEW

FAYYAZ AHMEDFAYYAZ AHMEDHULL & EAST YORKSHIRE HOSPITALS HULL & EAST YORKSHIRE HOSPITALS

NHS TRUSTNHS TRUST

LEARNING OUTCOMELEARNING OUTCOME

The Current management strategy for common The Current management strategy for common primary headache disordersprimary headache disorders

Appraisal of currently available treatmentsAppraisal of currently available treatments New treatments on the horizonNew treatments on the horizon

Primary Headache Disorders: Primary Headache Disorders: Frequency ClassificationFrequency Classification

Primary Headache disorders

Secondary Headache disorders

Paroxysmal Headache

Attack Duration < 4 hours +/or

Discrete episodes

Long lasting Headache

Daily or near daily headache

Duration > 4 hours per day

Chronic MigraineChronic

Tension-type headache

New Daily Persistent headache

Hemicrania Continua

Adapted from Silberstein et al., Neurology (1996) 47: 871-

With or withoutmedication overuse

Episodic

Chronic

EPISODIC VERSUS CHRONICEPISODIC VERSUS CHRONIC

EPISODICEPISODIC MIGRAINEMIGRAINE TENSION HEADACHETENSION HEADACHE CLUSTER HEADACHECLUSTER HEADACHE

CHRONICCHRONIC CHRONIC MIGRAINECHRONIC MIGRAINE CHRONIC TENSION TYPE HEADACHECHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHEMEDICATION OVERUSE HEADACHE CHRONIC CLUSTER HEADACHECHRONIC CLUSTER HEADACHE

04/18/2304/18/23

Episodic Migraine; How to Episodic Migraine; How to manage?manage?

Identify any obvious triggersIdentify any obvious triggers

Infrequent attacksInfrequent attacks Acute treatment onlyAcute treatment only

Frequent attacksFrequent attacks Acute and Preventative treatmentsAcute and Preventative treatments

04/18/2304/18/23

7

High Percentage of Migraine High Percentage of Migraine Patients Report TriggersPatients Report Triggers

76% to 95% of patients report triggers*,1

The mean number of triggers per patient is 6.71

Stress has been shown to be even more important in chronic migraine than in episodic migraine2

0

20

40

60

80

100

Stress Hormones NotEating

Weather SleepDisturb.

Perfume/Odor

Neck Pain

Lights Alcohol Smoke SleepingLate

Heat Food

Pe

rce

nt

of

Pa

tie

nts

Triggers

1. Kelman L Cephalalgia 2007;27:394–402. 2. Radat F et al. Cephalalgia 2009;29:338–350.

*Percentage of patients reporting depends on how the question is asked.

ACUTE TREATMENT OF ACUTE TREATMENT OF MIGRAINE ATTACKMIGRAINE ATTACK

Ergot (1868)Ergot (1868) Salicylic acid (1870)Salicylic acid (1870) Ergotamine Ergotamine Dihydroergotamine (DHE)Dihydroergotamine (DHE) Triptans in early 90’s (Triptans in early 90’s (working on 5 HT1 receptorsworking on 5 HT1 receptors))

SumatriptanSumatriptan RizatriptanRizatriptan EletriptanEletriptan AlmotriptanAlmotriptan ZolmitriptanZolmitriptan NaratriptanNaratriptan FrovatriptanFrovatriptan

04/18/2304/18/23 99

Standard abortive Standard abortive therapytherapy

Migraine; How to manage?Migraine; How to manage?

Acute Rx: Key MessageAcute Rx: Key Message

Avoid opiates or combination analgesics with Avoid opiates or combination analgesics with barbiturates, caffeine barbiturates, caffeine

Restrict the use to no more than two Restrict the use to no more than two days/doses per weekdays/doses per week

NSAID has the lowest potential for medication NSAID has the lowest potential for medication overuse overuse

New Rx on the HorizonNew Rx on the Horizon

CGRP antagonists or GepantsCGRP antagonists or Gepants Glutamate Receptor AntagonistsGlutamate Receptor Antagonists Vanilloid (TRPV1) receptor antagonistsVanilloid (TRPV1) receptor antagonists Nitric Oxide Synthetase inhibitorsNitric Oxide Synthetase inhibitors Prostanoid Receptor Antagonist Prostanoid Receptor Antagonist

New ways of Established RxNew ways of Established Rx

Inhaled version of DHEInhaled version of DHE (MAP-004 - LEVADEX(MAP-004 - LEVADEX©©) )

TriptansTriptans Melts and spraysMelts and sprays Needle free injection (intraject)Needle free injection (intraject) Transdermal patches (Zelrix)Transdermal patches (Zelrix) Sumnap (sumatriptan Naproxen combination)Sumnap (sumatriptan Naproxen combination)

MIGRAINE PROPHYLAXISMIGRAINE PROPHYLAXIS

04/18/23 13

When should I give migraine prophylaxis?When should I give migraine prophylaxis?

Prophylaxis is used to reduce the number of attacks in circumstances when acute therapy, used appropriately, gives inadequate symptom control. (BASH GUIDELINES

2010)

04/18/2304/18/23

14

Consensus view on migraine Consensus view on migraine prophylaxisprophylaxis

Should be offered to patients with 6 or more headache Should be offered to patients with 6 or more headache days per month; 4 or more days with some impairment; or days per month; 4 or more days with some impairment; or 3 or more days with severe functional impairment3 or more days with severe functional impairment

Should be considered with 4–5 days per month with Should be considered with 4–5 days per month with normal functioning; 3 days with some impairment and 2 normal functioning; 3 days with some impairment and 2 days with severe impairmentdays with severe impairment

Should not be given to patients with <4 days of headache Should not be given to patients with <4 days of headache per month with normal functioning; or no more than 1 day per month with normal functioning; or no more than 1 day per month regardless of impairmentper month regardless of impairment

1. Lipton RB et al. Neurology 2007;68:343–349.

04/18/2304/18/23

15

Migraine prophylaxis Migraine prophylaxis treatment optionstreatment options

Non-pharmacologicalNon-pharmacological1,21,2

Behavioural lifestyle changesBehavioural lifestyle changes Anxiety management, psychotherapy and Anxiety management, psychotherapy and

physiotherapyphysiotherapy

PharmacologicalPharmacological Few agents specifically licensed for migraine Few agents specifically licensed for migraine

prophylaxisprophylaxis

1. World Health Organization (WHO) in collaboration with the European Headache Federation (EHF). J Headache Pain 2007;8:S1–47. 2. Lipchik GL. American Headache Society, 2008. www.achenet.org/education/BiofeedbackRelaxationTrainingforHeadaches.asp Accessed April 2012.

04/18/2304/18/23

16

Non-drug interventionsNon-drug interventions

Acupuncture has little benefit, if any at allAcupuncture has little benefit, if any at all Physiotherapy for the neck as an adjunctive treatment Physiotherapy for the neck as an adjunctive treatment

may be usefulmay be useful Indian head massage may be useful but the evidence is Indian head massage may be useful but the evidence is

anecdotalanecdotal Relaxation therapy, stress reduction and coping strategies Relaxation therapy, stress reduction and coping strategies

are helpfulare helpful These interventions are in need of formal evaluationThese interventions are in need of formal evaluation Yoga and meditation are said to enhance stress Yoga and meditation are said to enhance stress

management and appeal to some peoplemanagement and appeal to some people11

Homeopathy offers no valueHomeopathy offers no value22

1. BASH Guidelines 2010. http://216.25.88.43/upload/NS_BASH/BASH_guidelines_2010.pdf  Accessed March 2012. 2. Whitmarsh TE et al. Cephalalgia 1997;17:600–4.

04/18/2304/18/23

17

Pharmacological options for Pharmacological options for migraine prophylaxismigraine prophylaxis1,21,2

Amine modulation:Amine modulation: Beta blockersBeta blockers 5-HT blockers (pizotifen, methysergide)5-HT blockers (pizotifen, methysergide)

Channel modulation:Channel modulation: Anticonvulsants (topiramate, epilim*)Anticonvulsants (topiramate, epilim*)

Tricyclic AntidepressantsTricyclic Antidepressants Amitriptyline*Amitriptyline*

ACE inhibition:ACE inhibition: Lisinopril*Lisinopril*

* Currently not licensed for migraine prophylaxis in the UK* Currently not licensed for migraine prophylaxis in the UK

1. BASH 2010. http://216.25.88.43/upload/NS_BASH/BASH_guidelines_2010.pdf Accessed August 2011. 2. Scottish Intercollegiate Guidelines Network 2008. http://www.sign.ac.uk/guidelines/fulltext/107/index.html .

04/18/2304/18/23

18

Beta blockersBeta blockers

First-line if not contraindicated by asthma, heart failure, First-line if not contraindicated by asthma, heart failure, peripheral vascular disease or depression peripheral vascular disease or depression

Use of propranolol in migraine prophylaxisUse of propranolol in migraine prophylaxis11:: 58 propranolol studies met the inclusion criteria, of which 58 propranolol studies met the inclusion criteria, of which

26 were placebo controlled 26 were placebo controlled Overall relative risk of response to treatment was 1.94 Overall relative risk of response to treatment was 1.94

(95% CI 1.61 to 2.35)(95% CI 1.61 to 2.35) 17 trials showed a significant superiority over placebo, 7 a 17 trials showed a significant superiority over placebo, 7 a

trend for propranolol and 2 no differencetrend for propranolol and 2 no difference

Commonly reported adverse events include cold extremities, Commonly reported adverse events include cold extremities, reduced exercise tolerance, nightmares and dizzinessreduced exercise tolerance, nightmares and dizziness

1. Linde K et al. Cochr Database of Syst Rev 2004, Issue 2. Art. No.: CD003225.

04/18/2304/18/23

19

AmitriptylineAmitriptyline

Used widely second only to beta-blockersUsed widely second only to beta-blockers 3 small trials of amitriptyline (all before 1987) show 21–42% 3 small trials of amitriptyline (all before 1987) show 21–42%

reduction in number of attacksreduction in number of attacks May be used first-line when migraines co-exist with May be used first-line when migraines co-exist with

troublesome tension-type headache, another chronic pain troublesome tension-type headache, another chronic pain condition, disturbed sleep or depressioncondition, disturbed sleep or depression

Commonly reported adverse events include dry mouth, Commonly reported adverse events include dry mouth, sedation, dizziness and nauseasedation, dizziness and nausea11

Dose used ranges between 10 and 150 mg per dayDose used ranges between 10 and 150 mg per day11

Individual tolerance to dosages varies and titration is Individual tolerance to dosages varies and titration is highly dependent on side-effects experiencedhighly dependent on side-effects experienced

1. Amitriptyline Summary of Product Characteristics 2009. Rosemount Pharmaceuticals Limited.

04/18/2304/18/23

20

TopiramateTopiramate

Clinical trials suggest efficacy equal to sodium valproateClinical trials suggest efficacy equal to sodium valproate11

Use of topiramate in migraine prophyalxisUse of topiramate in migraine prophyalxis22:: 6 (of 6) topiramate studies showed overall superiority to 6 (of 6) topiramate studies showed overall superiority to

placebo in the combined analysis (OR 3.34; 95% CI 2.36 to placebo in the combined analysis (OR 3.34; 95% CI 2.36 to 4.73) with noticeable variation in the odds ratio across the 4.73) with noticeable variation in the odds ratio across the studiesstudies22

A dose of 100 mg reports a 50% response rateA dose of 100 mg reports a 50% response rate33 Cognitive side effects and tingling sensation in fingers and Cognitive side effects and tingling sensation in fingers and

toes often limit its usetoes often limit its use Around a quarter of patients report loss of weight of Around a quarter of patients report loss of weight of

around 10% and can act as a mood stabiliseraround 10% and can act as a mood stabiliser

1. Shaygannejad V et al. Headache 2006;46: 642–8. 2. Chronicle EP et al. Cochr Database of Syst Rev 2004, Issue 3. Art. No.: CD003226. 3. Mathew N et al. Neurology 2003;60(Suppl. 1): A336.

04/18/2304/18/23

21

ValproateValproate

Sodium valproate has a response rate of around 44%Sodium valproate has a response rate of around 44%11 It does not reduce the efficacy of hormonal contraception It does not reduce the efficacy of hormonal contraception Use of valproate in migraine prophyalxisUse of valproate in migraine prophyalxis22::

4 (of 4) valproate studies showed active treatment was superior to 4 (of 4) valproate studies showed active treatment was superior to placebo in reduction in migraine frequency placebo in reduction in migraine frequency (OR 3.34; 95%CI 1.46 to 7.67)(OR 3.34; 95%CI 1.46 to 7.67)22

Adverse events reported include nausea, asthenia, somnolence, weight gain Adverse events reported include nausea, asthenia, somnolence, weight gain and alopeciaand alopecia

Blood cell count, platelet count, bleeding time and coagulation tests are Blood cell count, platelet count, bleeding time and coagulation tests are recommended prior to starting treatment and in case of spontaneous recommended prior to starting treatment and in case of spontaneous bruising or bleeding bruising or bleeding

Liver dysfunction is reported rarely Liver dysfunction is reported rarely

1. Klapper J Cephalalgia 1997;17: 103–8. 2. Chronicle EP et al. Cochr Database of Syst Rev 2004, Issue 3. Art. No.: CD003226.

04/18/2304/18/23

Few Clinical Trials Have Focused on Few Clinical Trials Have Focused on Preventive Pharmacotherapy in Preventive Pharmacotherapy in

Chronic MigraineChronic Migraine

22

TreatmentTreatment Evidence for Use in Chronic MigraineEvidence for Use in Chronic Migraine

Anticonvulsants:Anticonvulsants: ValproateValproate TopiramateTopiramate Gabapentin Gabapentin

Small double-blind, placebo-controlled in CMSmall double-blind, placebo-controlled in CM1,21,2

Double-blind, placebo-controlled trials in CMDouble-blind, placebo-controlled trials in CM3,43,4

One double-blind, placebo-controlled trial in CDHOne double-blind, placebo-controlled trial in CDH55

Antidepressants:Antidepressants: AmitriptylineAmitriptyline Fluoxetine Fluoxetine Tizanidine Tizanidine

Small open-label trial in TMSmall open-label trial in TM66

Small double-blind, placebo-controlled trial in CDHSmall double-blind, placebo-controlled trial in CDH77

Small double-blind, placebo-controlled trial in CDHSmall double-blind, placebo-controlled trial in CDH88

Beta-blockersBeta-blockers No evidence that they are effective in CMNo evidence that they are effective in CM

Calcium channel blockersCalcium channel blockers No evidence that they are effective in CMNo evidence that they are effective in CM

ACE inhibitors and ARBsACE inhibitors and ARBs No evidence that they are effective in CMNo evidence that they are effective in CM

1. Yurekli VA et al. J Headache Pain 2008;9:37–41. 2. Bartolini M et al. Clin Neuropharmacol 2005;28:277–279. 3. Diener HC et al. Cephalalgia 2007;27:814–823. 4. Silberstein SD et al. Headache 2007;47:170–180. 5. Spira PJ et al. Neurology 2003;61:1753–1759. 6. Krymchantowski AV et al. Headache 2002;45:510–514. 7. Saper JR et al. Headache 1994;34:497–502. 8. Saper JR et al. Headache 2002;42:470–482.

ACE = angiotensin-converting enzyme;ARB = angiotensin receptor blocker.

EPISODIC VERSUS CHRONICEPISODIC VERSUS CHRONIC

EPISODICEPISODIC MIGRAINEMIGRAINE TENSION HEADACHETENSION HEADACHE CLUSTER HEADACHECLUSTER HEADACHE

CHRONICCHRONIC CHRONIC MIGRAINE (CM)CHRONIC MIGRAINE (CM) CHRONIC TENSION TYPE HEADACHECHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHE MEDICATION OVERUSE HEADACHE

(MOH)(MOH) CHRONIC CLUSTER HEADACHECHRONIC CLUSTER HEADACHE

Chronic MigraineChronic MigraineThe IHS 2006 Revised The IHS 2006 Revised

ClassificationClassificationpreviously Triptan/Ergot responsive?previously Triptan/Ergot responsive?

Headache on Headache on >> 15 days month 15 days month

with with featuresfeatures of Migraine type of Migraine type

headacheheadache

On On >> 8 days / month* 8 days / month*

for > 3 months for > 3 months without other cause without other cause

of headacheof headache

With or without Analgesic Medication Overuse Headache?

*ICHD-2 = Previously >15

CHRONIC MIGRAINECHRONIC MIGRAINE

Under-diagnosed and Under-treatedUnder-diagnosed and Under-treated Most disabling form of headache disorderMost disabling form of headache disorder11

Co-morbidities are more commonCo-morbidities are more common22

Trigger factors more pronounced than episodic Trigger factors more pronounced than episodic varietyvariety33

50-80% overuse painkillers50-80% overuse painkillers44

Patients may have low pain threshold and abnormal Patients may have low pain threshold and abnormal cortical processingcortical processing55

1. Blumenfield, 2011 2. Buse 2009 3. Kelman 2007 4. Allena 20091. Blumenfield, 2011 2. Buse 2009 3. Kelman 2007 4. Allena 2009

26

Chronic Migraine: Chronic Migraine: Multifaceted Approach to TherapyMultifaceted Approach to Therapy

Chronicmigraine

management

Education, support, managing expectations, and

close follow-up

Lifestyle modifications,

behavioral therapy

Pharmacologic therapy

Dodick DW N Engl J Med 2006;354:158–165.

CM and MOH: ControversyCM and MOH: Controversy

IHS criteria exclude MO in defining CMIHS criteria exclude MO in defining CM11

Preventive treatment first or deal with MOHPreventive treatment first or deal with MOH2,3,42,3,4

Does MO reduce efficacy of preventive agent?Does MO reduce efficacy of preventive agent?55

Topiramate trial showed equal response in both Topiramate trial showed equal response in both arms i.e. with or without MOHarms i.e. with or without MOH66

1.1. ICHD II 2006ICHD II 2006 2. Hagen J Headache Pain 20102. Hagen J Headache Pain 20103.3. Lovell Curr Opin Neurol 2010Lovell Curr Opin Neurol 2010 4. Rossi Euro J of Neurol 20104. Rossi Euro J of Neurol 20105. 5. Hagen Cephalalgia 2009Hagen Cephalalgia 2009 6. Deiner Cephalalgia 2007 6. Deiner Cephalalgia 2007

GREATER OCCIPITAL NERVE GREATER OCCIPITAL NERVE BLOCK (GON)BLOCK (GON)

Local anaesthetic +/- SteroidsLocal anaesthetic +/- Steroids 50% respond for up to 1 month50% respond for up to 1 month1,21,2

20% no benefit20% no benefit33

Local discomfort and alopeciaLocal discomfort and alopecia44

1. Afridi Pain 20061. Afridi Pain 2006 2. Ashkenazi JNNP 2007 3. Shields Neurology 20042. Ashkenazi JNNP 2007 3. Shields Neurology 2004

4. Tobin & Fitman Headache 20094. Tobin & Fitman Headache 2009

• 2 Trials: PREEMPT1 and PREEMPT 2• Phase 3, parallel-group, placebo-controlled studies of Botulinum toxin

A 155-195U in Chronic Migraine

1384 patients randomised (Botulinum toxin A 688, Placebo 696)31 injections per treatment session

Botulinum Toxin A in Chronic MigraineBotulinum Toxin A in Chronic MigrainePREEMPT StudiesPREEMPT Studies

Diener HC et al., Cephalalgia. 2010 Jul;30(7):804-14Aurora SK et al., Cephalalgia. 2010 Jul;30(7):793-803Dodick DW et al., Headache. 2010 Jun;50(6):921-36

p<0.001

Nearly 70% of Nearly 70% of patients treated with patients treated with BOTOXBOTOX®® throughout throughout the entire study the entire study experienced ≥50% experienced ≥50% reduction in migraine reduction in migraine days from baseline at days from baseline at Week 56 (67.8% vs. Week 56 (67.8% vs. 59.6% for placebo; 59.6% for placebo; p=0.018)p=0.018)33

Mean ± standard error.The double-blind phase included 688 subjects in the BOTOX® group and 696 in the placebo group. Migraine days at baseline: 19.1 BOTOX® group vs 18.9 placebo group, p=0.328.

1. Dodick DW et al. Headache 2010;50:921–936.2. Aurora SK et al. Presented at IHC 2009.3. Allergan Data on File – 50% responder rate at Week 56.

Mea

n c

han

ge

in f

req

uen

cy m

igra

ine

day

s fr

om

bas

elin

e (d

ays/

28-d

ay p

erio

d)

52484440363228241612840

Study week

020 56

-2

-4

-6

-8

-10

-12

-14

BOTOX® (n=688)

Placebo (n=696)

p=0.018

p=0.01

p=0.024

p=0.013p=0.003

p=0.006p=0.003

p<0.001

p<0.001p<0.001

p<0.001

p<0.001

Double-blind phase:BOTOX® vs. placebo Open-label phase:

All patients on BOTOX®

Mea

n c

han

ge

in f

req

uen

cy o

f m

igra

ine

day

s fr

om

bas

elin

e (d

ays/

28-d

ay p

erio

d)

p<0.001

PREEMPT POOLED ANALYSIS: MEAN CHANGE FROM BASELINE IN FREQUENCY OF MIGRAINE DAYS

TRANSCRANIAL TRANSCRANIAL MAGNETIC STIMULATIONMAGNETIC STIMULATION

TMS devices deliver a brief magnetic TMS devices deliver a brief magnetic pulse to the scalp and underlying pulse to the scalp and underlying cortex, altering firing patternscortex, altering firing patterns

targets cortical spreading depression targets cortical spreading depression (CSD)(CSD) CSD is a wave ofCSD is a wave of

excitation followedexcitation followedby a wave ofby a wave ofinhibitioninhibition

04/18/23 33

Transcranial Magnetic Stimulation for Migraine: A safety Review: Dodick et al Headache 2010;50(7):1153-63

22

16

39

29

0

10

20

30

40

50

pain free 2 hr Sustained pain free 2-24 hr

Sham Active

(Lipton et al., Lancet Neurol 2010;9:373-380)

% P

atie

nts

Transcranial magnetic stimulation for migraine• Randomised double-blind placebo controlled study

• Include: 30% aura episodes, aura leads to headache 90%• Exclude: Prolonged aura, MOH• TMS- 0.9T for 180 ms; Sham- click and vibrate• Primary endpoint: 2 hr pain free plus non-inferiority for nausea/photo/phono• Blinding: Thought they got active, 67% Sham and 72% active

n = 82 82

*

Occipital Nerve Stimulator: St Jude’s Occipital Nerve Stimulator: St Jude’s device device

CE MarkedCE Marked Chronic Migraine Chronic Migraine

and intractable TACand intractable TAC

04/18/23 35

96

27

39

40

0

10

20

30

40

50

reduction in headache days 50 % responder rate

Pre-set Adjustable Medically managed

(Saper et al., AHS 2008)

%Occipital nerve stimulation in chronic

migraineONSTIM• Double-blind randomized parallel group sham stimulation controlled study

***

n = 16 29 17

NS

*P = 0.032; **P = 0.003

Single Blind, Prospective Feasibility Study N = 66

Failed two preventive Rx

-3.9

-2.6

-4.8-5.5

-5.9

-5

-8

-6

-4

-2

0migraine days migraine days- no MOH migraine days- +MOH

Sham- 1us, 10Hz, <1mA, 1s on 90min off

Active- 250usec/60Hz, 0-12mA

(Lipton et al., Cephalalgia 2009;29:30- IHC2009)

days

Occipital nerve stimulation in migraine & chronic migraine-

PRISM

n = 62 63

NS

Double blind randomised parallel group sham stimulation controlled study on patients failed two preventative treatments

Prospective DB controlled N = 132

Trial Stimulation Negative Study

Gamma Core Vagal Nerve StimulatorGamma Core Vagal Nerve Stimulator

Received CE MarkedReceived CE Marked Low ampere Low ampere

StimulationStimulation Prophylaxis as well Prophylaxis as well

as acute Treatment. as acute Treatment.

04/18/23 38

MOH: DefinitionMOH: DefinitionIHS 2004, Revised 2005*, Appendix IHS 2004, Revised 2005*, Appendix

Criteria 2006Criteria 2006

Headache present on Headache present on >> 15 d/month for > 3 months 15 d/month for > 3 months Regular overuse for > 3 months ofRegular overuse for > 3 months of

Triptan or ergot or opiates or combination analgesics Triptan or ergot or opiates or combination analgesics >> 10 10 d/monthd/month

Simple analgesics or combination with above Simple analgesics or combination with above >> 15 d/month 15 d/month Headache developed or worsened during overuseHeadache developed or worsened during overuse

** Probable until headache improves after withdrawal Probable until headache improves after withdrawal

Which Medication?Which Medication?

Combination analgesic 39-42%Combination analgesic 39-42% Simple Analgesic 29-38%Simple Analgesic 29-38% Triptans 12-20%Triptans 12-20% Opiates 6%Opiates 6% Ergotamine 4-11%Ergotamine 4-11%

MOH develops faster with triptan than simple MOH develops faster with triptan than simple analgesics and similarly withdrawal symptoms are analgesics and similarly withdrawal symptoms are much milder with triptansmuch milder with triptans

Relja et al Headache 2004Relja et al Headache 2004

Zeeberg et al Cephalalgia 2006Zeeberg et al Cephalalgia 2006

Katsarava et al 2000,2001Katsarava et al 2000,2001

MOH: Rx StrategyMOH: Rx Strategy

How?How? Abrupt or GradualAbrupt or Gradual Abrupt with simple analgesic/triptanAbrupt with simple analgesic/triptan Gradual with combination analgesic, opiatesGradual with combination analgesic, opiates44

Worse before better; short duration for rebound with Worse before better; short duration for rebound with triptan than combination and opiatestriptan than combination and opiates11

When?When? Before or after preventiveBefore or after preventive

Where? Where? IP or OPIP or OP OP as first line and brief IP if no motivation or failed OP as first line and brief IP if no motivation or failed

OPOP2,32,3

1. Diener and Katsarava 2001 2. Hering and Steiner 1991 3. Rossi et al 2006 4. Everz & Marziniak 20101. Diener and Katsarava 2001 2. Hering and Steiner 1991 3. Rossi et al 2006 4. Everz & Marziniak 2010

What to expect after What to expect after withdrawal?withdrawal?

70% get worse70% get worse

Withdrawal symptoms of Withdrawal symptoms of nausea, vomiting, sleep nausea, vomiting, sleep disturbance and autonomic disturbance and autonomic symptomssymptoms

Katsarava et al 2002Katsarava et al 2002

Headache intensity worsens at day 2-4 before improvement

Rx for withdrawal symptomsRx for withdrawal symptoms

Steroids: controversialSteroids: controversial1,2,31,2,3

Naproxen 500 mg bd 10-20 daysNaproxen 500 mg bd 10-20 days44

IV DHE intermittent/continuous +/- IV DHE intermittent/continuous +/- metoclopramidemetoclopramide5,6,75,6,7

IV ValproateIV Valproate88

IV clonidineIV clonidine99, Prochlorperazine, Prochlorperazine1010, Tizanidine, Tizanidine1111

1. Krymchantowski and Barbosa 2000 2. Pagelar et al 2008 3. Boe et al 2008 4. 1. Krymchantowski and Barbosa 2000 2. Pagelar et al 2008 3. Boe et al 2008 4. Mitsikostas and Jumah 2011 5. Boes et al 2006 6. Silberstein et al 1991 7. Ford and Ford Mitsikostas and Jumah 2011 5. Boes et al 2006 6. Silberstein et al 1991 7. Ford and Ford 1997 8. Schwartz et al 2003 9. Silberstein et al 2006 10. Le et al 2000 11. Smith 20021997 8. Schwartz et al 2003 9. Silberstein et al 2006 10. Le et al 2000 11. Smith 2002

PROGNOSIS OF MOHPROGNOSIS OF MOH

2 WEEKS2 WEEKS 23% COMBINATION 23% COMBINATION

ANALGESICSANALGESICS 85% TRIPTANS85% TRIPTANS

ONE YEARONE YEAR 35-60%35-60%

5 YEARS5 YEARS 50% RELAPSE50% RELAPSE

85%

57%

23%

EPISODIC VERSUS CHRONICEPISODIC VERSUS CHRONIC

EPISODICEPISODIC MIGRAINEMIGRAINE TENSION HEADACHETENSION HEADACHE

CLUSTER HEADACHECLUSTER HEADACHE CHRONICCHRONIC

CHRONIC MIGRAINE (CM)CHRONIC MIGRAINE (CM) CHRONIC TENSION TYPE HEADACHECHRONIC TENSION TYPE HEADACHE MEDICATION OVERUSE HEADACHE (MOH)MEDICATION OVERUSE HEADACHE (MOH)

CHRONIC CLUSTER HEADACHECHRONIC CLUSTER HEADACHE

EPISODIC CLUSTER HEADACHEEPISODIC CLUSTER HEADACHE

100% oxygen 4-8 litres/min or 100% oxygen 4-8 litres/min or immigran sc injection 6 mg or nasal immigran sc injection 6 mg or nasal spray for acute attackspray for acute attack

Steroids to induce remissionSteroids to induce remission VerapamilVerapamil MethysergideMethysergide PizotifenPizotifen TopiramateTopiramate GabapentinGabapentin

CHRONIC CLUSTER HEADACHECHRONIC CLUSTER HEADACHE

LithiumLithium Other drugs used in episodicOther drugs used in episodic Can be refractory Can be refractory

GON injectionGON injection ONSONS Deep Brain StimulationDeep Brain Stimulation

INDOMETACIN RESPONSIVE INDOMETACIN RESPONSIVE HEADACHEHEADACHE

Absolute ResponseAbsolute Response Paroxysmal HemicraniaParoxysmal Hemicrania Hemicrania ContinuaHemicrania Continua

Partial ResponsePartial Response Primary Stabbing headachePrimary Stabbing headache Hypnic HeadacheHypnic Headache Primary cough, exertional or coital Primary cough, exertional or coital

headacheheadache

THANKSTHANKS

JOIN BASHJOIN BASH ELECTRONIC OR PAPER COPY OF ELECTRONIC OR PAPER COPY OF

CEPHALALGIACEPHALALGIA REGULAR NEWSLETTERSREGULAR NEWSLETTERS INVITATION TO BASH EVENTSINVITATION TO BASH EVENTS ABILITY TO CONTRIBUTE TO RESEARCH ABILITY TO CONTRIBUTE TO RESEARCH

THROUGH INTERACTIVE WEBSITE (ABOUT THROUGH INTERACTIVE WEBSITE (ABOUT TO LAUNCH)TO LAUNCH)