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Recent Advances:
Migraine
Guide: Dr Raakhi
Tripathi
JR-2: Dr Anup
Petare
20/09/2015 Department of Pharmacology & Therapeut...
Recent Advances:
Migraine
Guide: Dr Raakhi
Tripathi
JR-2: Dr Anup
Petare
20/09/2015 Department of Pharmacology & Therapeut...
Overview
• Definition
• Epidemiology
• Types/Classification/Grades
• Pathogenesis
• Current therapy
• Recent advances
20/0...
20/09/2015 Department of Pharmacology & Therapeutics 4
Migraine is a chronic neurological disorder characterized
by recurr...
20/09/2015 Department of Pharmacology & Therapeutics 5
Migraine
Disabling Primary Headache disorder
Ranked 19th by the WHO...
20/09/2015 Department of Pharmacology & Therapeutics 6
Two major sub-types,
Migraine without aura (common migraine)
• Head...
20/09/2015 Department of Pharmacology & Therapeutics 7
Grades of Migraine
Mild migraine: may be one attack per month throbbing
but tolerable headache lasting upto 8 hours which ...
20/09/2015 Department of Pharmacology & Therapeutics 9
Pathogenesis
Vascular
theory
Neurogenic
theory
Neurogenic
inflammat...
20/09/2015 Department of Pharmacology & Therapeutics 10
Neurovascular Theory
20/09/2015 Department of Pharmacology & Therapeutics 11
Signaling cascade
Current therapeutic option..
Acute
treatment
Preventive
treatment
Behavioural
treatment
To reduce pain and
duration of att...
Acute/ Abortive therapy
Non-specific treatment:
NSAID’s
Specific treatment:
Ergot alkaloids
5-HT receptor agonist
(Triptan...
Acute therapy: Triptans
Selective 5-HT 1B/1D agonist
 Sumatriptan
 Almotriptan
 Eletriptan
 Frovatriptan
 Naratriptan...
Acute / Abortive therapy
Failed analgesics or NSAIDs
Oral Sumatriptan 50 mg or 100 mg, Rizatriptan 10mg
Almotriptan 12.5 m...
 Early nausea or difficulties taking tablets
Sumatriptan 20 mg nasal spray, Zolmitriptan 5 mg nasal
spray, Rizatriptan 10...
Contraindications to Triptans
 Coronary artery disease
 Hypertension
 Peripheral vascular disease
 Hemiplegic or Basil...
Preventive therapy
Beta- blockers
 Propranolol
 Metoprolol
 Timolol
Calcium channel blockers
 Flunarizine
 Verapamil
...
Recent advances
 New FDA approvals
 New uses of existing drugs
 Drugs in pipeline
 New devices
Recent Advances: In acute Treatment
20/09/2015 Department of Pharmacology & Therapeutics 20
Brandes JL, Kudrow D, Stark SR...
20/09/2015 Department of Pharmacology & Therapeutics 21
Reduction in migraine frequency in patients with chronic migraine ...
20/09/2015 Department of Pharmacology & Therapeutics 22
 New FDA approvals
TOPAMAX
• March 28, 2014: 1st FDA approval for prophylaxis of
migraine headaches in adolescents ages 12 to 17
(100mg)
• AD...
Treximet
• Treximet (Sumatriptan/Naproxen Sodium) Formerly
Known as TREXIMA,
• May 2012: Menstrual Migraine in Women With
...
Zomig (Zolmitriptan)
• October 2008: USFDA approved Zomig (zolmitriptan)
Nasal Spray
• Jan 2015: Treatment of Acute Migrai...
BOTOX®
(OnabotulinumtoxinA)
20/09/2015 Department of Pharmacology & Therapeutics 26
• 15 Oct 2010 USFDA approved Botox inj...
Transdermal patch:
Sumatriptan
20/09/2015 Department of Pharmacology & Therapeutics 27
January 2013, FDA approved: acute
m...
20/09/2015 Department of Pharmacology & Therapeutics 28
• Otopoint-needle implant can effectively relieve
headache in migr...
 New uses of existing drugs
Dexamethasone addition to standard
acute therapy
 Proposed to prevent recurrence of migraine through its
prevention of ne...
Carvedilol
 Additional alpha-1 blocking and antioxidant properties
 A very favourable adverse event profile
 A prospect...
Tiagabine (TGB)
 Inhibits the neuronal and glial reuptake of GABA and therefore
enhances GABA-mediated inhibition
 Open-...
Levetiracetam
 Promising drug for the treatment of transformed migraine
 Open label trial in 36 transformed migraine pat...
Zonisamide
Unique combination of pharmacologic actions:
 Blocks voltage-dependent sodium and T-type calcium
channels
 Re...
Quetiapine
 Atypical antipsychotic drug with a high affinity for D4
receptors
 Also possesses,
 High affinity for 5-HT2...
Tizanidine hydrochloride
 Alpha-2-adrenergic presynaptic agonist that inhibits the
release of norepinephrine in the brain...
Petasites/Butterbur
 Extract from the plant Petasites hypridus (butterbur)
 Inhibits peptide-leukotriene biosynthesis, p...
20/09/2015 Department of Pharmacology & Therapeutics 38
Holland PR, Akerman S, Andreou AP, Karsan N, Wemmie JA, Goadsby PJ...
20/09/2015 Department of Pharmacology & Therapeutics 39
20/09/2015 Department of Pharmacology & Therapeutics 40
 Drugs in pipeline
20/09/2015 Department of Pharmacology & Therapeutics 41
Phase 3: Completed
TARGET:A Randomized,
Double-Blind, Placebo-Cont...
20/09/2015 Department of Pharmacology & Therapeutics 42
NXN-188
• 20 July 2014 trial NXN 188 for the Treatment of
Migraine...
20/09/2015 Department of Pharmacology & Therapeutics 43
Levadex (Dihydroergotamine)
• Multi-center trial, FREEDOM-301, con...
20/09/2015 Department of Pharmacology & Therapeutics 44
• Glutamate receptors antagonist
• In 2007 Phase 2 was completed
h...
Telcagepant (MK-0974)
• In 2010 merck terminated it study with Telcagepant
(0974-049)
• Terminated: Identification of two ...
20/09/2015 Department of Pharmacology & Therapeutics 46
Edvinsson L. CGRPreceptor antagonism in migraine treatment. Lancet...
20/09/2015 Department of Pharmacology & Therapeutics 47
 New devices
20/09/2015 Department of Pharmacology & Therapeutics 48
• 13 December 2013: FDA allows marketing of first device to
reliev...
Cefaly
20/09/2015 Department of Pharmacology & Therapeutics 49
http://www.accessdata.fda.gov/cdrh_docs/pdf12/k122566.pdf
•...
Conclusion
• <60% migraine patients respond & tolerate preventatives1
• Need for better options for the
symptomatic and pr...
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Recent Advances in migraine

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Recent Advances in migraine

  1. 1. Recent Advances: Migraine Guide: Dr Raakhi Tripathi JR-2: Dr Anup Petare 20/09/2015 Department of Pharmacology & Therapeutics 1
  2. 2. Recent Advances: Migraine Guide: Dr Raakhi Tripathi JR-2: Dr Anup Petare 20/09/2015 Department of Pharmacology & Therapeutics 2
  3. 3. Overview • Definition • Epidemiology • Types/Classification/Grades • Pathogenesis • Current therapy • Recent advances 20/09/2015 Department of Pharmacology & Therapeutics 3
  4. 4. 20/09/2015 Department of Pharmacology & Therapeutics 4 Migraine is a chronic neurological disorder characterized by recurrent attacks of headache widely variable in intensity, frequency and duration. Attacks are commonly unilateral and are usually associated with anorexia, nausea and vomiting. Migraine - World Federation of Neurology
  5. 5. 20/09/2015 Department of Pharmacology & Therapeutics 5 Migraine Disabling Primary Headache disorder Ranked 19th by the WHO among all diseases world-wide causing disability IHS: migraine constitutes 16% of primary headaches In India, 15-20% of people suffer from migraine with M:F ratio of 1:2 WHO: Severe migraine can be as disabling as quadriplegia
  6. 6. 20/09/2015 Department of Pharmacology & Therapeutics 6 Two major sub-types, Migraine without aura (common migraine) • Headache with specific features and associated symptoms Migraine with aura (classic migraine) • Focal neurological symptoms that usually precede or sometimes accompany the headache. • Some experience premonitory phase, occurring hours or days before the headache, and a headache resolution phase
  7. 7. 20/09/2015 Department of Pharmacology & Therapeutics 7
  8. 8. Grades of Migraine Mild migraine: may be one attack per month throbbing but tolerable headache lasting upto 8 hours which does not incapacitate the individual Moderate migraine: The throbbing headache more intense, lasts for 6-24 hours, nausea/vomiting and other features are more prominent patient is functionally impaired. One or more attacks occur per month. Severe migraine: 2-3 or more attacks per month of severe throbbing headache lasting 12-48 hours, often accompanied by vertigo, vomiting and other symptoms; the subject grossly incapacitated during the attack. 20/09/2015 Department of Pharmacology & Therapeutics 8
  9. 9. 20/09/2015 Department of Pharmacology & Therapeutics 9 Pathogenesis Vascular theory Neurogenic theory Neurogenic inflammation Aura results from intracranial vaso- constriction Headache results from subsequent rebound vasodilatation Cortical spreading depression of the electrical activity followed by vascular phenomena Triggered by Trigeminal sensory system mediated by 5-HT, neurokinin, substance P, calcitonin gene related peptide (CGRP), nitric oxide, etc.
  10. 10. 20/09/2015 Department of Pharmacology & Therapeutics 10 Neurovascular Theory
  11. 11. 20/09/2015 Department of Pharmacology & Therapeutics 11 Signaling cascade
  12. 12. Current therapeutic option.. Acute treatment Preventive treatment Behavioural treatment To reduce pain and duration of attack To reduce frequency of attacks and disability  Identification of triggers  Meditation  Psychotherapy
  13. 13. Acute/ Abortive therapy Non-specific treatment: NSAID’s Specific treatment: Ergot alkaloids 5-HT receptor agonist (Triptans)
  14. 14. Acute therapy: Triptans Selective 5-HT 1B/1D agonist  Sumatriptan  Almotriptan  Eletriptan  Frovatriptan  Naratriptan  Rizatriptan  Zolmitriptan Similar efficacy Differing Pharmacokinetic profile
  15. 15. Acute / Abortive therapy Failed analgesics or NSAIDs Oral Sumatriptan 50 mg or 100 mg, Rizatriptan 10mg Almotriptan 12.5 mg, Eletriptan 40 mg, Zolmitriptan 2.5 mg For slower effect or better tolerability: Oral Naratriptan 2.5 mg, Frovatriptan 2.5 mg Infrequent headache: Ergotamine 1-2 mg oral, Dihydroergotamine nasal spray 2 mg Headache recurrence Ergotamine 2 mg (perhaps most effective taken rectally, usually with caffeine) Oral Naratriptan 2.5 mg and Eletriptan 80 mg
  16. 16.  Early nausea or difficulties taking tablets Sumatriptan 20 mg nasal spray, Zolmitriptan 5 mg nasal spray, Rizatriptan 10 mg dissolvable wafer, zolmitriptan 2.5 mg dispersible tablet ± Anti-emetics  Early vomiting Sumatriptan 25 mg suppository, Sumatriptan 6 mg subcutaneous injection ± Anti-emetics  Rapidly developing symptoms Sumatriptan 6 mg subcutaneous injection, Dihydroergotamine 1 mg intramuscular injection Acute / Abortive therapy
  17. 17. Contraindications to Triptans  Coronary artery disease  Hypertension  Peripheral vascular disease  Hemiplegic or Basilar migraine  Avoid in those on Ergots, SSRI and TCA  Pregnancy and Lactation  Should not be used for more than 2 days a week to decrease the possibility of rebound headache
  18. 18. Preventive therapy Beta- blockers  Propranolol  Metoprolol  Timolol Calcium channel blockers  Flunarizine  Verapamil Tricyclic antidepressants  Amitryptiline  Nortryptiline Anti-epileptics/ Neurostabilizers  Topiramate  Divalproex sodium  Gabapentin Serotonin antagonists  Pizotifen  Methysergide Serotonergic agents  Dihydroergotamine
  19. 19. Recent advances  New FDA approvals  New uses of existing drugs  Drugs in pipeline  New devices
  20. 20. Recent Advances: In acute Treatment 20/09/2015 Department of Pharmacology & Therapeutics 20 Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, Alexander WJ, Spruill SE, Barrett PS, Lener SE. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297:1443–54. doi: 10.1001/jama.297.13.1443.
  21. 21. 20/09/2015 Department of Pharmacology & Therapeutics 21 Reduction in migraine frequency in patients with chronic migraine with analgesic overuse. Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L. Topiramate in the treatment of chronic migraine. Cephalalgia. 2003;23:820–4. doi: 10.1046/j.1468- 2982.2003.00592.x. Silberstein SD, et L Topiramate Chronic Migraine Study Group Efficacy and safety of topiramate for the treatment of chronic migraline: a randomised, doubleblind, placebo- controlled trial. Headache. 2007;47:170–80. doi: 10.1111/j.15264610.2006.00684.x. Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ, TOPMATMIG201(TOP CHROME) Study Group Topiramate reduces headache days in chronic migrai a randomised, doubleblind, placebocontrolled study. Cephalalgia. 2007;27:814–23. doi: 10.1111/j.14682982.2007.01326.x.
  22. 22. 20/09/2015 Department of Pharmacology & Therapeutics 22  New FDA approvals
  23. 23. TOPAMAX • March 28, 2014: 1st FDA approval for prophylaxis of migraine headaches in adolescents ages 12 to 17 (100mg) • ADR: paresthesia, upper respiratory infection, anorexia, abdominal pain 20/09/2015 Department of Pharmacology & Therapeutics 23
  24. 24. Treximet • Treximet (Sumatriptan/Naproxen Sodium) Formerly Known as TREXIMA, • May 2012: Menstrual Migraine in Women With Dysmenorrhea Phase 3 study was completed 20/09/2015 Department of Pharmacology & Therapeutics 24 https://clinicaltrials.gov/ct2/show/NCT00329459?term=Imitrex+menstrual+migraine&rank=1
  25. 25. Zomig (Zolmitriptan) • October 2008: USFDA approved Zomig (zolmitriptan) Nasal Spray • Jan 2015: Treatment of Acute Migraine Headache in Adolescents (TEENZ) Phase 4 study was completed 20/09/2015 Department of Pharmacology & Therapeutics 25
  26. 26. BOTOX® (OnabotulinumtoxinA) 20/09/2015 Department of Pharmacology & Therapeutics 26 • 15 Oct 2010 USFDA approved Botox inj : Prevent headaches in adult patients with chronic migraine. every 12 weeks as multiple injections around the head and neck • ADR: neck pain and headache. • Boxed warning: Botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism
  27. 27. Transdermal patch: Sumatriptan 20/09/2015 Department of Pharmacology & Therapeutics 27 January 2013, FDA approved: acute medication sumatriptan delivery by new mechanism (transdermal patch) ADR: Painful sensation at the patch application site, reddening
  28. 28. 20/09/2015 Department of Pharmacology & Therapeutics 28 • Otopoint-needle implant can effectively relieve headache in migraine patients • Upregulate plasma 5-HT level. http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/654/CN-00778654/frame.html accessed on 3.4.2015. Acupuncture:
  29. 29.  New uses of existing drugs
  30. 30. Dexamethasone addition to standard acute therapy  Proposed to prevent recurrence of migraine through its prevention of neurogenic inflammation  7 Randomized clinical trials (n = 742)  Dexamethasone vs placebo (both + standard therapy): Dexa group was less likely to experience recurrent headache within 24 to 72 hours  Conclusion: Dexamethasone appears to be safe and modestly effective addition to standard migraine abortive therapy for the prevention of migraine recurrence Giuliano C, Smalligan RD, Mitchon G, Chua M. Role of dexamethasone in the prevention of migraine recurrence in the acute care setting: a review. Postgrad Med. 2012 May;124(3): 110-5
  31. 31. Carvedilol  Additional alpha-1 blocking and antioxidant properties  A very favourable adverse event profile  A prospective, open-label trial in 76 patients with doses titrated from 3.125 mg/day to 6.25 mg twice daily over 2 weeks revealed,  50% reduction in monthly migraine attack frequency at the third month of treatment in 59% patients,  But, 26% patients withdrew due to lack of efficacy or as a result of adverse events Bigal ME, Krymchantowski AV. Emerging Drugs for Migraine Prophylaxis and Treatment. Medscape General Medicine. 2006;8(2):31.
  32. 32. Tiagabine (TGB)  Inhibits the neuronal and glial reuptake of GABA and therefore enhances GABA-mediated inhibition  Open-label study in 41 patients with refractory migraine using a mean dose of 10 mg/day TGB revealed,  5 patients experienced a remission of their migraine attacks  33 patients had at least a 50% reduction in their attacks  Side effects reported were dizziness, asthenia, tremor and abdominal pain  Safety alert issued in 2005: Risk of new onset seizures and status epilepticus in patients without a history of epilepsy
  33. 33. Levetiracetam  Promising drug for the treatment of transformed migraine  Open label trial in 36 transformed migraine patients with 1000 mg/day of LCT revealed significant reduction in headache frequency at 1 month and 3 months  Efficacy and safety evaluated in 30 patients ( aged 6 – 19 years) with paediatric migraine with 125 – 250 mg BD revealed,  At least 50% reduction in headache frequency and severity in 17 patients with improved quality of life  Used off-label for migraine prophylaxis Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B. Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study. Clin Neuropharmacol. 2006 Nov-Dec;29(6):338-42 Miller GS. Efficacy and safety of levetiracetam in pediatric migraine. Headache. 2004 Mar;44(3):238-43
  34. 34. Zonisamide Unique combination of pharmacologic actions:  Blocks voltage-dependent sodium and T-type calcium channels  Reduces glutamate-mediated excitatory neurotransmission  Inhibits excessive nitric oxide (NO) production, scavenging hydroxyl and NO radicals  Inhibits carbonic anhydrase All of these mechanisms may play a role in headache and pain modulation possibly via neuronal stabilization 2 open-label trials: One in 33 patients and second in 34 patients with refractory migraine with 100 mg/day Zonisamide showed, Significant reduction in frequency and severity of migraine Side effects reported included paraesthesia, fatigue, anxiety, and weight loss Bermejo PE, Dorado R. Zonisamide for migraine prophylaxis in patients refractory to topiramate. Clin Neuropharmacol. 2009 Mar-Apr;32(2):103-6
  35. 35. Quetiapine  Atypical antipsychotic drug with a high affinity for D4 receptors  Also possesses,  High affinity for 5-HT2 receptors  Partial agonistic activity at 5-HT1A receptors  Blocking activity at alpha1-adrenergic receptors  In an open label pilot study in 34 pts with refractory migraine, 75.9% presented > 50% headache reduction Potential for migraine prophylaxis Krymchantowski AV, Jevoux C. Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study. Arq Neuropsiquiatr. 2008 Sep;66(3B):615-8.
  36. 36. Tizanidine hydrochloride  Alpha-2-adrenergic presynaptic agonist that inhibits the release of norepinephrine in the brainstem and spinal cord  An open study of 220 patients demonstrated efficacy in chronic migraine  Evidence supports tizanidine as an effective prophylactic adjunct for chronic daily headache  Also, possible importance of an alpha2-adrenergic mechanism underlying the pathophysiology of migraine is suggested Saper JR, Lake AE 3rd, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache. 2002 Jun;42(6):470-82.
  37. 37. Petasites/Butterbur  Extract from the plant Petasites hypridus (butterbur)  Inhibits peptide-leukotriene biosynthesis, possibly through calcium channel regulation  efficacy in migraine prevention was studied in 2 trials,  A small RCT reported: low dose of petasites, 50 mg twice daily, significantly reduced the number of migraine attacks per month and the number of migraine days per month  A larger RCT over 5 month by Lipton and colleagues reported: 4-month mean attack count reduced by 48% in patients treated with petasites 75 mg twice daily, by 34% with petasites 50 mg
  38. 38. 20/09/2015 Department of Pharmacology & Therapeutics 38 Holland PR, Akerman S, Andreou AP, Karsan N, Wemmie JA, Goadsby PJ. Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura. Ann Neurol. 2012 Oct;72(4):559-63. doi: 10.1002/ana.23653. PubMed PMID: 23109150. Acid-sensing ion channel 1 • Novel therapeutic target for migraine with aura. • Amiloride: Shown to block cortical spreading depression via this mechanism
  39. 39. 20/09/2015 Department of Pharmacology & Therapeutics 39
  40. 40. 20/09/2015 Department of Pharmacology & Therapeutics 40  Drugs in pipeline
  41. 41. 20/09/2015 Department of Pharmacology & Therapeutics 41 Phase 3: Completed TARGET:A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of a Single 20 mg Dose of Sumatriptan Powder Delivered Intra-nasally with the Bi-Directional Device in Adults With Acute Migraine With or Without Aura Head-to-Head Comparison Trial: COMPASS: Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-Directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura PG Djupesland, P Dočekal, the Czech Migraine Investigators Group Intranasal sumatriptan powder delivered by a novel breath-actuated bi- directional device for the acute treatment of migraine: A randomised, placebo-controlled study Cephalalgia August 2010 vol. 30 no. 8 933-942
  42. 42. 20/09/2015 Department of Pharmacology & Therapeutics 42 NXN-188 • 20 July 2014 trial NXN 188 for the Treatment of Migraine With Aura completed its Phase 2 • Immediate release oral product • Novel mechanism, selective inhibition of neuronal Nitric Oxide Synthase (nNOS), as well as 5-HT1B/1D activation
  43. 43. 20/09/2015 Department of Pharmacology & Therapeutics 43 Levadex (Dihydroergotamine) • Multi-center trial, FREEDOM-301, consisted of a randomized, double blind, placebo-controlled • 16 April 2013 USFDA issued Complete Response Letter on NDA of Levadex raising concern over manufacturing process for the final filled canisters.
  44. 44. 20/09/2015 Department of Pharmacology & Therapeutics 44 • Glutamate receptors antagonist • In 2007 Phase 2 was completed https://clinicaltrials.gov/ct2/show/NCT00567086?term=tezampanel&rank=1 Tezampanel (NGX424MIG2001)
  45. 45. Telcagepant (MK-0974) • In 2010 merck terminated it study with Telcagepant (0974-049) • Terminated: Identification of two patients with significant elevations in serum transaminases • 27 Jan 2015: Phase 3 study of Telcagepant (MK-0974-011) in Participants With Moderate to Severe Acute Migraine With or Without Aura 20/09/2015 Department of Pharmacology & Therapeutics 45 https://clinicaltrials.gov/ct2/show/NCT00442936?term=telcagepant&rank=1 • Antagonist of the receptor for CGRP
  46. 46. 20/09/2015 Department of Pharmacology & Therapeutics 46 Edvinsson L. CGRPreceptor antagonism in migraine treatment. Lancet. 2008;372:2089–90. doi:10.1016/S01406736(08)617109. ADX10059
  47. 47. 20/09/2015 Department of Pharmacology & Therapeutics 47  New devices
  48. 48. 20/09/2015 Department of Pharmacology & Therapeutics 48 • 13 December 2013: FDA allows marketing of first device to relieve migraine headache pain (Cerena) • Device delivers Pulse transcranial magnetic stimulation at the onset of headache or aura • Disrupts cortical spreading depression www.accessdata.fda.gov/cdrh_docs/pdf13/den130022.pdf Cerena
  49. 49. Cefaly 20/09/2015 Department of Pharmacology & Therapeutics 49 http://www.accessdata.fda.gov/cdrh_docs/pdf12/k122566.pdf • 11 March 2014: USFDA approved device for preventing migraine. • Transcutaneous Electrical Nerve Stimulator to Treat Headache • Warnings: Indicated for use by adults and should only be used for 20 minutes/day, • ADR: Tingling or massaging sensation where electrode applied.
  50. 50. Conclusion • <60% migraine patients respond & tolerate preventatives1 • Need for better options for the symptomatic and preventative treatment of migraine • future seems bright as understanding of the disease improving newer and safer treatment are rising. 20/09/2015 Department of Pharmacology & Therapeutics 50 1: Pascual J. Recent advances in the pharmacological management of migraine. F1000 Med Rep. 2009 May 8;1. pii: 39. doi: 10.3410/M1-39. PubMed PMID: 20948742; PubMed Central PMCID: PMC2924709.

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