1. Acute and preventive treatments for migraine Mark Weatherall BASH public meeting High Wycombe 2012

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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)

8. 3. Non-pharmacological measures lifestyle issues – the ‘boring life’? trigger management ◦ hormonal ◦ dietary ◦ psychological  CBT, relaxation ◦ environmental ◦ sleep ◦ neck...

9. 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

10. 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

11. Variations on a theme if early nausea, you can use: soluble aspirin suppositories*: ◦ diclofenac 75 mg ◦ domperidone 30 mg *be French!

14. Problems, problems… not effective ◦ dose? timing? route? combination? diagnosis? contraindications ◦ asthma, upper GI problems, renal impairment side effects ◦ GI, CNS

15. This is what patients do next

16. Codeine…? … is NOT a treatment for headache ◦ the WHO analgesic ladder should NOT be applied to headache management

17. Triptans 5-HT 1B/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

18. Headache response at 2 hr

19. Pain freedom at 2 hr

20. advantagesdisadvantages Sumatriptanwell-established expensive available OTCpoorly absorbed now the cheapest s/c, nasal spray Zolmitriptancheaperoccasional confusion long acting nasal spray, melt Naratriptancheaper slow onset long acting Rizatriptanrapid onsethigh recurrence melt Almotriptancheaper low SE incidence Eletriptancheaperpumped out of CNS long acting Frovatriptanlongest half-life slow onset

21. Problems, problems… ineffective ◦ dose? timing? route? switch? headache recurrence ◦ switch? combination with NSAID? contraindications ◦ HT, IHD SE ◦ nausea, GI, CNS, ‘triptan chest’

23. Then... 9. Avoid medication overuse 10. Use prophylactic treatments appropriately

24. 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

25. 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)

26. 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)

27. 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

28. 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

29. 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