Acute treatment of migraine

1. Acute treatment of migraine Mark Weatherall BASH meeting, Hull 2009

3. The intangibles • Doctor-patient relationship • Realistic expectations • Education

4. Triggers • Hormonal • Dietary • Psychological • Environmental • Sleep • Drugs

6. 10 steps to success • Make the diagnosis • Use the right drugs • Use effective doses • Treat early when the pains mild • Treat associated symptoms

7. 10 steps to success • Choose appropriate route of delivery • Observe contraindications • Use prior experience to select/reject drugs • Avoid drugs with high potential for MOH • Combine medications if necessary

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

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

14. Headache response at 2 hr

15. Problems, problems… • Not effective • dose? timing? route? combination? • Contraindications • asthma, upper GI problems, renal impairment • Side effects • GI, CNS

16. This is what patients do next

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

18. 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

20. Which triptan?

21. Headache response at 2 hr

22. Pain freedom at 2 hr

25. advantages disadvantages Sumatriptan well-established expensive £4.60 available OTC poorly absorbed s/c (£22.10), melt (£4.14), nasal spray (£6.14) Zolmitriptan cheaper occasional confusion £4.00 long acting nasal spray (£6.75), melt (£4.00) Naratriptan cheaper slow onset £4.09 long acting Rizatriptan rapid onset high recurrence £4.46 melt (£4.46) Almotriptan cheaper £3.02 low SE incidence Eletriptan cheaper pumped out of CNS £3.75 long acting Frovatriptancheapest slow onset £2.78 longest half-life

26. Problems, problems… • Ineffective • dose? timing? route? switch? • Headache recurrence • switch? combination with NSAID? • Contraindications • HT, IHD • SE • nausea, GI, CNS, ‘triptan chest’

28. Is the future ‘pants’? • CGRP antagonists • two with data recently published • proof-of-concept trial of intravenous BIBN4096BS (now called olcagepant) was published in NEJM in 2004 • phase II study of oral CGRP antagonist MK-0974 (now called telcagepant) presented at IHS 2007 and published in Neurology in 2008

29. multicentre phase III R-PT-PC-DB-T of oral telcagepant 150 or 300 mg vs zolmitriptan 5 mg and placebo published in The Lancet in last four weeks

34. A&E/in-patient options • sumatriptan s/c 6 mg • alternatively nasal spray 20 mg • high dose NSAIDs • aspirin 1 g • (available as IV formulation – useful as rescue medication in medication withdrawal) • indometacin 100 mg • (can be given IM)

35. Refractory migraine • dihydroergotamine (DHE) 0.5-1.0 mg iv/im (2 mg nasal spray) • anticonvulsants • sodium valproate 500 mg iv in 100 mL normal saline over 15 min • (? role for SVP infusion in status migrainosus) • clonazepam 1 mg/mL slow push

36. … or … • dopamine antagonists • metoclopramide 10-20 mg IV • (rpt to 30-60 mg over 2 hrs) • droperidol 0.625 mg every 10 mins • (average effective dose 3.15 mg) • prochlorperazine 10 mg iv over 2 min • (may rpt after 30 min) • metoclopramide & prochlorperazine can be followed with DHE 0.5-1.0 mg over 10 mins

37. … or … • magnesium sulphate 1 g iv over 15 min • dexametasone 8-20 mg iv over 5-10 min; hydrocortisone 100-250 mg iv over 10 min, every 8-12 hrs for 24 hours • (again, useful in status) • ketorolac 30-60 mg iv/im

38. A final thought: listening is therapy in itself … and you’ve listened long enough!