IV Pharmacological Approaches to Treating Migraine & Pain in the Clinic

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1 IV Pharmacological Approaches to Treating Migraine & Pain in the Clinic John Claude Krusz, PhD, MD Medical Director Anodyne Headache and Pain Care, Dallas & Grapevine, Texas PAIN44

2 Channels Ions (carriers of current) Na +, Ca ++, Mg ++, K + Na+ : NAP, multiple forms (cloned) Ca++ : good guy; excitotoxic in excess Mg++ : physiologic antagonist to Ca++, blocks Ca++ entry at NMDA glutamate receptor K+: repolarization, can block glutamate release

3 Neurotransmitters Good guys: 5HT, NE Enkephalins, endorphins Ketamine [NMDA receptor blockade] Mg ++

4 STRATEGIES INPATIENT Cost, time, inconvenien ce DHE45 protocol often a mainstay [after 25 years!!] Ins co won t pay often sleep quality is ignored OUTPATIENT more convenient much cheaper than average cost of ED visit! (over $4000) in our hands a much higher success rate On demand, with the right attitude

5 OUR STORY FOR OUTPATIENT TREATMENT success defined as >50% reduction in level of headache/pain severity with treatment [ie, a #8/10 reduced to #3/10 or less] 62/1874 refractory headaches/migraines were successfully treated in the clinic 96% success rate 34 of 62 retreated in clinic 14 of 22 went to ED 14/62 elected not to retreat

6 Acute Treatment is not about Medication ITS ABOUT OUTCOME AND PRODUCTIVITY

7 Acute IV Interventions in the Clinic All IV (often with pulse oximetry monitoring) dihydroergotamine (DHE-45) mg usually with metoclopromide (Reglan) 10 mg q 1-2 hrs MgSO4-1 to 2 gm in NS w/ or w/o dexamethasone (Decadron) 4-6 mg or ketorolac 30-60mg over 1 hour valproate sodium (Depacon) mg over 5 to 10 minutes; can repeat dose methocarbamol (Robaxin) mg over 1-2 hours other antinauseants: metochlopramide droperidol mg q15 min; ondansetron IV 2-4mg prn

8 More Exotic All IV lidocaine (needs pulse oximetry) propofol (needs pulse oximetry) ketamine (needs pulse oximetry) IV tramadol not available in US IV levetiracetam IV baclofen (not available in US)

9 MgSO 4 Antagonist for calcium (bad guy in excess) Therefore, blocks glutamate (bad guy)- that s a good thing!! Fairly inexpensive recent shortage Few side effects Can turn down flare-ups of pain, headache and muscle spasm

10 Dexamethasone Steroid anti-inflammatory agent (potent and clean) can be used orally as well for short course Often used with MgSO 4 or many other agents

11 DHE-45 Can be used IV or IM First published in 1987 High success rates Pre-medicate with antinauseant Affects multiple receptor types Available in Nasal Spray form [Migranal NS ] Recent success in pre-empting perimenstrual and early AM migraines * *Krusz, JC, Cammarata, D, Scott, V, AJPM, 16:78-83, 2006

12 Valproate sodium rapid dosing IV mg over 45 min can reduce/eliminate refractory migraines in clinic great treatment for status migrainosus More than 72 hrs of unremitting migraine Recent data with this submitted for publication* *Krusz, JC, Cagle, J, submitted Headache and Pain 2006

13 metochlopramide antinauseants can be dosed IM by patient promethazine older, drowsiness, not as potent prochlorperazine older etc droperidol can be given IM by patient micro dosing compared to regular use ondansetron, granisetron, dolasetron

14 Lidocaine Indiscriminate sodium channel blocking agent Can have predictive value for oral meds (about 5-6) Needs pulse oximetry monitoring Can be done repetitively during flare-ups Go slow, go long (3-6 hours)

15 propofol Anesthetic agent used in non-anesthetic [conscious sedation] doses Short half-life Very specific pharmacology GABA A receptors No p.o. equivalent

16 ketamine Blocks NMDA-type glutamate receptors Narrow therapeutic spectrum It can break a pain cycle It can reduce opioid tolerance tried in CRPS and neuropathic pain We have the largest database for refractory migraines, cluster, HC, CPH CDH and mixed headache disorders with pain

17 tramadol Does not exist in US available in Europe non-toxic with oral agent available Can lead to direct oral treatment without titration IV doses get into CNS better; sometimes can t be mimicked by po dosing

18 levetiracetam IND pending per speaker oral agent available- with efficacy in migraine and neuropathic pain shown non-toxic, no labs efficacy in cluster headache and TN

19 IV baclofen Powerful spasticity agent Gets into CNS well Not available in US po can be tried if IV works well

20 Ze Future Botulinum toxins for specific scenarios Intramuscular administration (usual) Intradermal administration (new)* New indication for CM Other treatments being developed CGRP inhibitors (on hold) CB1, CB2 antagonists VR1 and VR2 antagonists * Krusz JC, Poster presentation: AHS 44th Annual Scientific Meeting, Seattle, WA; June 21-23, 2002.

21 It s much easier to treat headaches today! Stay Tuned