Migraine: Past, Present and Future Edward O Sullivan September 12 th 2015 Dublin 12/09/2015

Transcription

1 1 Migraine: Past, Present and Future Edward O Sullivan September 12 th 2015 Dublin

2 Tour de France 2015: Mark Renshaw Yesterday at the end of the stage 17 I came down with a migraine before the final climb and the pain never went away overnight. I woke up with the same pain this morning. Its pain from really stiff muscles in my neck and has gone into my head in the form of a migraine. Every hole, every bump, every rough part of the road I could feel the pain in the back of my head I never experienced anything like this before there is no way I could keep going. 2

3 History of Migraine Ebers Papyrus 3,500 years ago. Hippocrates (400 B.C.): He seemed to see something shining before him like a light, usually in part of the right eye, at the end of a moment a violent pain supervened in the temple.and vomiting 3

4 Arataeus of Cappadocia 2 nd Century A.D. Episodic Attacks Unilateral one sided headaches Vomiting 4

5 Origin of term Migraine Greek and Latin Galen: 2 nd century A.D. Hemicrania Emigranea Migrana Megrim (1713) Migraine (1777) 5

6 History of Migraine 6

7 Skull Trepanation Prima Non Nocere 7

8 Understanding Migraine 1868: Dr.Woakes Ergot.derivative of rye plant Successfully treated 2 migraine patient with fungal extract from the rye plant.precursor to modern triptan therapies 8

9 Early Vascular Theories External Carotid Dr. Harold Wolffe 9

10 International Classification of Headache Disorders (1988) 10

11 11

12 1.1 Migraine without aura A. At least 5 attacks fulfilling criteria B-D B. Headache attacks lasting 4-72 h (untreated or unsuccessfully treated) C. Headache has 2 of the following characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (eg, walking, climbing stairs) D. During headache 1 of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis 12

13 1.2.1 Migraine with typical aura A. At least 2 attacks fulfilling criteria B and C B. Aura of visual, sensory and/or speech/language symptoms, each fully reversible, but no motor, brainstem or retinal symptoms C. 2 of the following 4 characteristics: 1. 1 aura symptom spreads gradually over 5 min, and/or 2 symptoms occur in succession 2. each individual aura symptom lasts 5-60 min 3. 1 aura symptom is unilateral 4. aura accompanied or followed in <60 min by headache D. Not better accounted for by another ICHD-3 diagnosis, and TIA excluded 13

14 Visual Aura Lashley s Aura: 1941 Visual Aura: Fortification spectra Gowers in the 1920 s 14

15 Cortical Spreading Depression: Laeo in

16 Migraine (1970 s and 80 s) Trigeminovascular Theory Trigeminovascular Theory 16

17 Migraine (1970 s and 80 s) Trigeminovascular Theory Trigeminovascular Theory Release of Neuropeptides 1. C.G.R.P. 2. Neurokinin 3. Substance P. 17

18 Acute Management of Migraine: 1991 Triptans :5-HT1B/1D Agonists Serotonin : 5-HT 18

19 Acute Management of Migraine:1991 The Triptans:5HT1B/1D Receptor Antagonists Mode of Action Sumatriptan Zolmitriptan Frovatriptan Almotriptan Eletriptan Naratriptan 19

20 Preventative Treatment of Migraine Reduction in Frequency / Duration / Severity of Attacks. On Rx for 3 months (1).B-Blockers (2). Pizotifen (3). Topiramate (4). Tricyclic- Antidepressants. 20

21 Chronic Migraine (2005) >15 days per month Present for > 3 months Duration: > 4 hours Many also may have Medication- Overuse 21

22 Recent Therapies: (2010) Chronic Migraine Botulinum Toxin >15 days per month Based on 2 clinical trials known as Preempt studies. Reduction in headache days 22

23 Neuromodulators: (2014) 23

24 W.H.O.: Global Burden of Disease 1.Low Back Pain 2.Major Depressive Disorder 3.Iron Defiency Anaemia 4.Neck Pain 5.COPD 6.Other Musculo-skeletal disorders 7. MIGRAINE 8. Diabetes 24

25 Unmet Needs Preventative Therapies Other Acute Therapies: i.e. Alternatives to triptan therapies. 25

26 C.G.R.P. Antagonists Phase 2 Clinical Trials Monoclonal antibodies Amg-334 Tev LY MK

27 C.G.R.P. Antagonists Amg-334 Phase 2 Clinical Trial Result: 62% of patients > 50% reduction in headache days 38% of patients > 75% reduction in headache days 19% of patients achieved complete remission 27

28 C.G.R.P. Antagonists Tev Phase 2 Clinical Trial Result: > 50% of patients > 50% reduction of headache days 33% of patients achieved a 75% reduction in headache frequency. 15% were headache free after 3 months 28

29 Acute Therapies: Alternative to Triptans Phase 2 Clinical Trial Results Lasmiditan: 5HT1F Antagonist 29

30 Lasmiditan: 5HT1F Receptor Antagonist 30