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.

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,Rapoport AM, Sheftell FD & Tepper SJ 2004Sheftell FD & Tepper SJ 2004

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,Rapoport AM, Sheftell FD & Tepper SJ 2004Sheftell FD & Tepper SJ 2004

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

35

71

84

84

87

0 25 50 75 100

% 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

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)

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

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, 2004Sheftell FD, Rapoport AM, 2004

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?

So... which is the best triptan?

• The one that works best for YOU!

• The triptans are more similar than different.

PostdromePostdromeProdromeProdrome Headache

Phases of The Migraine AttackWhen to Use Your Triptan

Associated Associated FeaturesFeatures

AuraAura

TimeTime

Inte

nsi

ty o

f S

ymp

tom

s o

r P

has

es

Early Intervention

Sheftell FD, Rapoport AM, 2004Sheftell 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

Migraine Preventive Agents

Beta blockersBeta blockers• PropranololPropranolol**• NadololNadolol• AtenololAtenolol• TimololTimolol**• MetoprololMetoprolol

Ca channel blockersCa channel blockers• VerapamilVerapamil• AmlodipineAmlodipine• DiltiazemDiltiazem• NifedipineNifedipine• NimodipineNimodipine• NisoldipineNisoldipine

AntidepressantsAntidepressants• TricyclicsTricyclics

– AmitriptylineAmitriptyline– NortriptylineNortriptyline

• MAOIsMAOIs• SSRIsSSRIs

– FluoxetineFluoxetine– SertralineSertraline– ParoxetineParoxetine

AntiepilepticsAntiepileptics• Divalproex sodiumDivalproex sodium**• GabapentinGabapentin• Topiramate Topiramate **• CarbamazepineCarbamazepine• DilantinDilantin• LamotrigineLamotrigine• TiagabineTiagabine• ZonegranZonegran• LevetiracetamLevetiracetam• OxcabazepineOxcabazepineNSAIDsNSAIDs

• NaproxenNaproxen• MeclofenamateMeclofenamate• IbuprofenIbuprofen• KetoprofenKetoprofen• FlurbiprofenFlurbiprofen

• CelecoxibCelecoxib• RofecoxibRofecoxib• ValdexcoxibValdexcoxib

5-HT5-HT22 antagonists antagonists• CyproheptadineCyproheptadine• Methysergide*Methysergide*• MethylergonovineMethylergonovine‡‡

Alternative therapiesAlternative therapies• RiboflavinRiboflavin• MagnesiumMagnesium• ??CyanocobalaminCyanocobalamin• Feverfew, Co Q 10Feverfew, Co Q 10• PetasitesPetasites

Others Others • ACE inhibitorsACE inhibitors• ARBs-candesartanARBs-candesartan• QuetiapineQuetiapine• TizanidineTizanidine• ??OpiatesOpiates

FutureFuture AMPA/Kainate AntagAMPA/Kainate Antag NOS inhibitorsNOS inhibitors ?? LT antagonists LT antagonists Botulinum toxinBotulinum toxin NMDA antagonistsNMDA antagonists CGRP antagonists CGRP antagonists CSD antagonistsCSD antagonists Adenosine A1 AgonAdenosine A1 Agon Pure 5-HTPure 5-HT1B/1D1B/1D Agon Agon

•

Sheftell FD, Rapoport AM, 2004Sheftell 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 depressionLT = leukotriene; CSD = cortically spreading depression

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

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

Thanks for your attention!