Acute and preventive Acute and preventive treatments for migrainetreatments for migraine

Mark WeatherallBASH public meetingHigh Wycombe 2012

To set the scene...To set the scene...“[Migraine] is a malady of which the student

gains little practical knowledge in the course of his hospital work, unless he is so unhappy as to learn from the most effective of all instructors, personal suffering... It is common enough, but seems, to most of its subjects, by long experience so much an inevitable part of life that few seek relief.”

William Gowers (1906)

“A doctor who cannot take a good history and a patient who cannot give one are danger of giving and receiving bad treatment”

Anonymous

10 steps to success10 steps to successGet the diagnosis rightSet realistic expectationsConsider non-pharmacological measuresUse the right drugsUse effective dosesTreat early when the pains mildTreat associated symptomsChoose appropriate route of deliveryAvoid medication overuseUse prophylactic treatments appropriately

1. Get the diagnosis right1. Get the diagnosis right‘migraine’ is the disorder and attack

◦a situation analogous to epilepsy the disorder epilepsy is a tendency to... the attack: seizures

◦in migraine, both share the same name◦the disorder is characterised by:

the tendency to repeated attacks triggers

sleep, food, weather, chemical (EtOH/GTN), hormonal, sensory, stress-relaxation

certain associations: hangovers, motion sickness, CVS family history

Migraine: Migraine: headache +headache +premonitory symptoms (20%+)

◦ tiredness , difficulty concentrating, neck stiffness, yawning, frequent urination – dopaminergic?

headaches typically unilateral, throbbing◦ associated with nausea +/- vomiting◦ sensitivity to light, sound, smells, movement

auras, usually visual, occur ~15-20% of patients◦ sensory, dysphasic, motor, olfactory

frequently associated with disability◦ WHO: a day of severe migraine ≈ quadriplegia

Migraine or TTH?Migraine or TTH?recognise the disorderphenotype the worst type of attackthe SPECTRUM study showed that

in patients with headaches that met criteria for migraine, probable migraine, and TTH, all headache types responded to triptans◦ this was not true for patients with purely TTH

chronic TTH is very rarerecurrent severe headaches are

migraine, until proven otherwise

2. Set realistic 2. Set realistic expectationsexpectationsthere is no ‘cure’recognising the disordergoal setting

◦trigger management◦effective acute treatment◦reducing attack frequency

explaining the natural historyarranging follow-up (if necessary)

3. Non-pharmacological 3. Non-pharmacological measuresmeasureslifestyle issues – the ‘boring life’?trigger management

◦hormonal◦dietary◦psychological

CBT, relaxation

◦environmental◦sleep◦neck...

Then...Then...

4. Use the right drugs4. Use the right drugs5. Use effective doses5. Use effective doses6. Treat early when the 6. Treat early when the painspains

mildmild7. Treat associated 7. Treat associated symptomssymptoms8. Choose appropriate route 8. Choose appropriate route ofof

deliverydelivery

Where to start?Where to start?paracetamol 1 gor, aspirin 900 mgor, ibuprofen 600-800 mg

◦+/- domperidone 10-20 mgtaken as soon as possible*ª

* i.e. as soon as the patient knows that this is a migraine or TTH

ª if there is aura, take at the start of the headache phase

Variations on a themeVariations on a themeif early nausea, you can use:soluble aspirinsuppositories*:

◦diclofenac 75 mg◦domperidone 30 mg

*be French!

Problems, problems…Problems, problems…not effective

◦dose? timing? route? combination? diagnosis?

contraindications◦asthma, upper GI problems, renal

impairmentside effects

◦GI, CNS

This is what patients do This is what patients do nextnext

Codeine…?Codeine…?… is NOT a treatment for

headache◦the WHO analgesic ladder should NOT be applied to headache management

TriptansTriptans5-HT1B/1D receptor agonistsseven different formulationsoptions for route of delivery

◦ oral tablets or melts◦ nasal spray◦ subcutaneous injection

taken as soon as possible*ª¹* i.e. as soon as the patient knows that this is a migraine

ª if there is aura, take at the start of the headache phase

¹ this is a race against the development of allodynia

Headache response at 2 Headache response at 2 hrhr

Pain freedom at 2 hrPain freedom at 2 hr

advantages disadvantages

Sumatriptan well-established expensiveavailable OTC poorly absorbednow the cheapests/c, nasal spray

Zolmitriptan cheaper occasional confusion

long actingnasal spray, melt

Naratriptan cheaper slow onsetlong acting

Rizatriptan rapid onset high recurrencemelt

Almotriptan cheaperlow SE incidence

Eletriptan cheaper pumped out of CNSlong acting

Frovatriptan longest half-life slow onset

Problems, problems…Problems, problems…ineffective

◦dose? timing? route? switch?headache recurrence

◦switch? combination with NSAID?contraindications

◦HT, IHDSE

◦nausea, GI, CNS, ‘triptan chest’

Then...Then...

9. Avoid medication 9. Avoid medication overuseoveruse

10. Use prophylactic10. Use prophylactictreatments treatments

appropriatelyappropriately

Choice of preventive RxChoice of preventive Rxlikelihood of responselikelihood of tolerabilityhelpful additional

properties◦ anxiolytic, antidepressant,

weight reduction

logistical issues◦ availability, monitoring

je ne sais quoi

First line preventivesFirst line preventivestricyclics

◦amitriptiline, dosulepin (50-100 mg)anticonvulsants

◦topiramate (50 mg bd), valproate (600-1000 mg)

β-blockers◦propranolol (40-80 mg tds), atenolol

(75-100 mg)pizotifen (1.5-2 mg)

Second line preventivesSecond line preventivesGON injection/sother anticonvulsants

◦pregabalin (300-600 mg)◦gabapentin (900-1200 mg)

vitamin B2 (400 mg)Mg citrate (600 mg)Coenzyme Q10 (450 mg)Botox (CM only – PREEMPT

protocol)

Long shots...Long shots...yet more

anticonvulsants◦ levetiracetam,

zonisamide, lamotrigine

methysergideflunarizinephenelzineaspirin/clopidogrelolanzapine

memantinemontelukasthigh-dose pizotifen lithiumamiloride in-patient therapies

◦ IV DHE, IV steroids,IV valproate, lidocaine

In the end...In the end...start low, go slow, but get thereuse all available avenues:

◦physio, CBT, biofeedback, specialist nurse

the law of diminishing returns applies

‘first do no harm’it is good to travel hopefully…

but it is better to arrive… eventually

The futureThe futurenew drugs with novel targets

◦ serotonin subtypes; CGRP; glutamate; TRPV1; nitric oxide; prostanoids; cortical spreading depression

new delivery mechanisms for existing drugs◦ inhaled DHE◦ inhaled, transdermal, needle-free triptans

transcranial magnetic stimulation