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Acute and preventive treatments for migraine. Mark Weatherall BASH public meeting High Wycombe 2012. To set the scene.
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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, stress-relaxation • 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 drugs5. Use effective doses6. Treat early when the pains mild7. Treat associated symptoms8. Choose appropriate route of delivery
Where to start? • paracetamol 1 g • 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
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
advantages disadvantages Sumatriptan well-established expensive available OTC poorly absorbed now the cheapest s/c, nasal spray Zolmitriptan cheaper occasional confusion long acting nasal spray, melt Naratriptan cheaper slow onset long acting Rizatriptan rapid onset high recurrence melt Almotriptan cheaper low SE incidence Eletriptan cheaper pumped out of CNS long acting 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 overuse10. 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