1. HCNE - BOSTON Massachussetts General Hospital November 4, 2004 Treatment of Headache ALAN M. RAPOPORT, M.D. Founder and Director The New England Center for Headache Stamford, Connecticut Clinical Professor of Neurology Columbia University College of Physicians & Surgeons New York, N.Y.

3. Headache Therapeutic Options Nonpharmacologic approaches Acute (abortive, symptomatic) therapy Preventive therapy Adjunctive therapies (Vitamins, Minerals, Supplements, Herbs): –Vitamin B-2 (400 mg per day) –Magnesium (400 mg per day) –Feverfew –Petasites –Coenzyme Q 10 (300 mg per day) Physical Techniques Rapoport AM,Sheftell FD & Tepper SJ 2004 Rapoport AM, Sheftell FD & Tepper SJ 2004

4. Nonpharmacologic Therapies for Headache Avoidance of triggers (e.g., dietary, weather, altitude, sleep and stress) Making lifestyle changes (e.g., eating regularly, going to sleep on schedule, and exercising on a regular basis) Behavioral therapies –Relaxation techniques –Biofeedback training –Stress management –Conflict resolution Rapoport AM,Sheftell FD & Tepper SJ 2004 Rapoport AM, Sheftell FD & Tepper SJ 2004

5. Goals of Acute Migraine Treatment Effective headache relief rapidly and consistently without recurrence →→ Pain Free State Restore the patient’s ability to function Minimize the use of rescue and backup medications Optimize self-care and reduce resource utilization Minimize side effects Be cost-effective

6. % Migraineurs Pain relief takes too long Doesn’t relieve all pain Doesn’t always work Headache comes back Too many side effects Reasons for Dissatisfaction with Current Treatment (U.S. Data) Lipton et al. Headache 1999;39:S20-S26

7. Classes of Medications for Acute Treatment of Migraine OTC simple analgesics NSAIDs and COX 2 Inhibitors Combination analgesics (Excedrin Migraine) Fiorinal ®, Fioricet ®, Esgic ®, Midrin ® Anti-nausea medication (Triptans) Ergots (Ergotamine and DHE) Opiates (Narcotics i.e Vicodin, Codeine)

8. What is the Syndrome of “Rebound Headache”? It is the increase in headache from the overuse of pain medications (now called MOH) Occurs only in patients with pre-existing chronic headache A self-sustaining rhythm of predictable and escalating medication use Headaches increase in frequency and intensity and become refractory to acute care and preventive treatments Medication withdrawal results in escalation of headache followed by improvement Rapoport AM, Sheftell FS & Tepper SJ 2004

9. TRIPTANS: Routes of Delivery Tablets Sumatriptan Zolmitriptan Naratriptan Rizatriptan Almotriptan Frovatriptan Eletriptan “Fast-melts” Rizatriptan - MLT Zolmitriptan - ZMT Suppository Sumatriptan (Europe ) Injection Sumatriptan Nasal Sprays Sumatriptan Zolmitriptan Sheftell FD, Rapoport AM, 2004

10. Which is the best Triptan? Many patients appear to be satisfied with the triptan they are taking But is it the ideal triptan for them? It may be. We ask 5 Questions to be sure: 1. How quickly does it start to work? 2. When has it reached maximum effect? 3. What % of the headache is gone? 4. Are there any side effects? 5. Does the headache recur within 24 hrs?

11. So... which is the best triptan? The one that works best for YOU! The triptans are more similar than different.

12. Postdrome Prodrome Headache Phases of The Migraine Attack When to Use Your Triptan AssociatedFeatures Aura Time Intensity of Symptoms or Phases Early Intervention

13. Sheftell FD, Rapoport AM, 2004 Indications for Preventive Strategies Frequency –Former: more than two attacks per month –Current: more than two attacks per week Disability/QOL related to headache Unresponsive to acute therapies Contraindications to acute therapies Significant adverse events with acute therapies Pharmacoeconomic considerations

14. Migraine Preventive Agents Beta blockers Propranolol* Propranolol* Nadolol Nadolol Atenolol Atenolol Timolol* Timolol* Metoprolol Metoprolol Ca channel blockers Verapamil Verapamil Amlodipine Amlodipine Diltiazem Diltiazem Nifedipine Nifedipine Nimodipine Nimodipine Nisoldipine NisoldipineAntidepressants Tricyclics Tricyclics – Amitriptyline – Nortriptyline MAOIs MAOIs SSRIs SSRIs – Fluoxetine – Sertraline – Paroxetine Antiepileptics Divalproex sodium* Divalproex sodium* Gabapentin Topiramate * Topiramate * Carbamazepine Carbamazepine Dilantin Dilantin Lamotrigine Lamotrigine Tiagabine Tiagabine Zonegran Zonegran Levetiracetam Levetiracetam Oxcabazepine Oxcabazepine NSAIDs Naproxen Naproxen Meclofenamate Meclofenamate Ibuprofen Ibuprofen Ketoprofen Ketoprofen Flurbiprofen Flurbiprofen Celecoxib Celecoxib Rofecoxib Rofecoxib Valdexcoxib Valdexcoxib 5-HT 2 antagonists Cyproheptadine Cyproheptadine Methysergide* Methysergide* Methylergonovine ‡ Methylergonovine ‡ Alternative therapies Riboflavin Riboflavin Magnesium ?Cyanocobalamin ?Cyanocobalamin Feverfew, Co Q 10 Feverfew, Co Q 10 Petasites PetasitesOthers ACE inhibitors ACE inhibitors ARBs-candesartan ARBs-candesartan Quetiapine Quetiapine Tizanidine Tizanidine ?Opiates ?Opiates Future AMPA/Kainate Antag AMPA/Kainate Antag NOS inhibitors NOS inhibitors ? LT antagonists ? LT antagonists Botulinum toxin Botulinum toxin NMDA antagonists NMDA antagonists CGRP antagonists CGRP antagonists CSD antagonists CSD antagonists Adenosine A1 Agon Adenosine A1 Agon Pure 5-HT 1B/1D Agon Pure 5-HT 1B/1D Agon Sheftell FD, Rapoport AM, 2004 Approved indication for migraine in US; †Not available in the US;Approved indication for migraine in US; †Not available in the US; ‡ Methylergometrine in Europe; NOS = nitric oxide synthase; ‡ Methylergometrine in Europe; NOS = nitric oxide synthase; LT = leukotriene; CSD = cortically spreading depression

15. Menstrual Migraine - Therapy 1. NSAIDs, eg. Naproxen Na 550 mg tid 2. COX 2 inhibitor eg. rofecoxib 50 mg qd 3. Pulsed estrogens + combo 4. Corticosteroids (dexamethasone) 5. Short burst of Triptans (all may help) 6. Pulsed methylergonovine, beta blockers, ergotamine tartrate, DHE Perimenstrual Pharmacologic Rx

16. Conclusion Get an accurate diagnosis from MD Don’t accept tension-type or sinus headaches as a diagnosis Don’t undertreat your migraine Don’t delay taking your medications Treat headache until pain-free

17. Thanks for your attention!