Acute treatment of migraine Mark Weatherall BASH meeting, Hull 2009

The intangibles Doctor-patient relationship Realistic expectations Education

Triggers Hormonal Dietary Psychological Environmental Sleep Drugs

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

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

Where to start? paracetamol 1 g or, aspirin 900 mg or, ibuprofen mg +/- domperidone 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

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

Headache response at 2 hr

Problems, problems… Not effective dose? timing? route? combination? 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-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

Which triptan?

Headache response at 2 hr

Pain freedom at 2 hr

advantagesdisadvantages Sumatriptanwell-established expensive £4.60available OTCpoorly absorbed s/c (£22.10), melt (£4.14), nasal spray (£6.14) Zolmitriptancheaperoccasional confusion £4.00long acting nasal spray (£6.75), melt (£4.00) Naratriptancheaper slow onset £4.09long acting Rizatriptanrapid onsethigh recurrence £4.46melt (£4.46) Almotriptancheaper £3.02low SE incidence Eletriptancheaperpumped out of CNS £3.75long acting Frovatriptancheapestslow onset £2.78longest half-life

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

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

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

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)

Refractory migraine dihydroergotamine (DHE) 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

… or … dopamine antagonists metoclopramide mg IV (rpt to mg over 2 hrs) droperidol 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 mg over 10 mins

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

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