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 gor, aspirin 900 mgor, 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

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-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

Which triptan?

Headache response at 2 hr

Pain freedom at 2 hr

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 actingnasal 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

Frovatriptan cheapest slow onset£2.78 longest 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) 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

… 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

… 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

A final thought: listening is therapy in itself

… and you’ve listened long enough!