Transcript Myaesthenia gravis

Acute and preventive treatments
for migraine
Mark Weatherall
BASH public meeting
High Wycombe 2012
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 success
Get the diagnosis right
 Set realistic expectations
 Consider non-pharmacological measures
 Use the right drugs
 Use effective doses
 Treat early when the pains mild
 Treat associated symptoms
 Choose appropriate route of delivery
 Avoid medication overuse
 Use prophylactic treatments appropriately

1. 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, stressrelaxation
 certain associations: hangovers, motion sickness, CVS
 family history
Migraine: 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?



recognise the disorder
phenotype the worst type of attack
the 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 rare
 recurrent severe headaches are migraine,
until proven otherwise

2. Set realistic expectations
there is no ‘cure’
 recognising the disorder
 goal setting

◦ trigger management
◦ effective acute treatment
◦ reducing attack frequency
explaining the natural history
 arranging follow-up (if necessary)

3. Non-pharmacological measures
lifestyle issues – the ‘boring life’?
 trigger management

◦ hormonal
◦ dietary
◦ psychological
 CBT, relaxation
◦ environmental
◦ sleep
◦ neck...
Then...
4. Use the right drugs
5. Use effective doses
6. Treat early when the pains
mild
7. Treat associated symptoms
8. Choose appropriate route of
delivery
Where to start?
 paracetamol
1g
 or, aspirin 900 mg
 or, ibuprofen 600-800 mg
◦ +/- domperidone 10-20 mg
 taken
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 theme
if early nausea, you can use:
 soluble aspirin
 suppositories*:

◦ diclofenac 75 mg
◦ domperidone 30 mg
*be French!
Problems, problems…

not effective
◦ dose? timing? route? combination? diagnosis?

contraindications
◦ asthma, upper GI problems, renal impairment

side effects
◦ GI, CNS
This is what patients do next
Codeine…?

… is NOT a treatment for headache
◦ the WHO analgesic ladder should NOT be
applied to headache management
Triptans



5-HT1B/1D receptor agonists
seven different formulations
options 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 hr
Pain freedom at 2 hr
advantages
disadvantages
Sumatriptan
well-established
available OTC
now the cheapest
s/c, nasal spray
expensive
poorly absorbed
Zolmitriptan
cheaper
long acting
nasal spray, melt
occasional confusion
Naratriptan
cheaper
long acting
slow onset
Rizatriptan
rapid onset
melt
high recurrence
Almotriptan
cheaper
low SE incidence
Eletriptan
cheaper
long acting
pumped out of CNS
Frovatriptan
longest half-life
slow onset
Problems, problems…

ineffective
◦ dose? timing? route? switch?

headache recurrence
◦ switch? combination with NSAID?

contraindications
◦ HT, IHD

SE
◦ nausea, GI, CNS, ‘triptan chest’
Then...
9. Avoid medication overuse
10. Use prophylactic
treatments appropriately
Choice of preventive Rx
likelihood of response
 likelihood of tolerability
 helpful additional
properties

◦ anxiolytic, antidepressant,
weight reduction

logistical issues
◦ availability, monitoring

je ne sais quoi
First line preventives

tricyclics
◦ 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 preventives
GON injection/s
 other 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...






yet more anticonvulsants

◦ levetiracetam, zonisamide,
lamotrigine

methysergide
flunarizine
phenelzine
aspirin/clopidogrel
olanzapine




memantine
montelukast
high-dose pizotifen
lithium
amiloride
in-patient therapies
◦ IV DHE, IV steroids,
IV valproate, lidocaine
In the end...
start low, go slow, but get there
 use 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 future

new 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