10/16/2012 Migraine Management in the Office • “23 yo patient into her second day of a migraine. Has taken sumatriptan Headache Treatment: Evidence‐based 100 mg yesterday morning, afternoon and at 4 AM this morning. She is miserable, in bed, with extreme nausea and vomited yesterday. She has Protocols for the Office and Emergency only been able to take sips of water. She calls your office nurse about what Department to do next”. • Anticipate the needs of your patients to avoid costly Sylvia Lucas MD, PhD and unpleasant urgent office or emergency Clinical Professor of Neurology & Rehabilitation Medicine department visits University of Washington Medical Center • Provide a written or easily referenced plan for urgent Seattle, Washington October 13, 2012 care to your patients • Re‐assess and modify treatment plans as needed Management Issues at First Visit Escalation of Migraine Pain Optimal Delivery • Initial therapy – Match treatment needs to attack profile, associated symptoms and level of disability (stratify the care) – Explain recurrence Fast • Back‐up therapy Intensity – If initial treatment fails • Rescue therapy Slow • Education – Treat early and optimally, lifestyle changes, avoid triggers Time Rescue therapy Urgent Care Delivery: The Outpatient Clinic Some Things to Consider • Patient has already used oral and usual • Transportation medication – Drugs may cause sedation or cognitive slowing • Injectable treatment used most often in office • Timing – PiPatient obibservation – Severe pain and later in the headache • Staffing – Gastroparesis, nausea or vomiting – Avoid being rushed: establish cut‐off times for calls • Both patient and physician desire rapid relief • Severity of Symptoms – Need resources for sicker patients – Rehydration or electrolyte imbalance may preclude – Need the room outpatient delivery 1 10/16/2012 Outpatient Treatment Protocols Outpatient Treatment Protocols A combination approach‐if infusion is not an option • Ask about medication allergy or drug hypersensitivity • Treatment with injectable anti‐nausea medication • Recent medication history (everything) – Dopamine antagonist if sedation is not an issue (e.g. prochlorperazine IM) • Be aware of maximum daily dosing to avoid toxicity – Ondansetron if sedation is to be avoided (e. g. 8 mg ODT) – Maximum daily dose of sumatriptan is 200 mg orally; 12 mg SQ; 20 mg nasal spray • Treatment with a migraine specific therapy – Maximum daily dose of DHE‐45® is 3 mg – Subcutaneous sumatriptan (usually 4‐6 mg SQ) – Use rational polypharmacy – DHE‐45® (usual dose 1 mg SQ or IM) • Respect half‐lives of medication and drug interactions • Treatment with injectable NSAID especially if allodynia is present (e.g. ketorolac 60 mg IM) Jakubowski M, Levy D, Goor-Areh I. et al. Headache 2005;45:850-861. Neuroleptics (D2 receptor antagonists) Dopamine Antagonists • Phenothiazines Medication Delivery and Dose Maximum Daily Dose – Prochlorperazine, chlorpromazine, promethazine Chlorpromazine 12.5 mg‐25 mg IM/IV 300 mg • Butyrophenones Droperidol 0.625 mg‐2.5 mg IV 10mg – DDidlroperidol, hhlaloperid idlol • Metoclopromide Prochlorperazine 5‐10 mg IM/IV 40 mg • Anti‐adrenergic, anti‐cholinergic, anti‐seritonergic, Promethazine 12.5‐25 mg IM/IV (AE w/IM) 100 mg anti‐histaminic effects Metoclopromide 5‐10 mg IM/IV 60 mg – Sedation, drowsiness, EPS – Prevent EPS (dystonia and akasthesia) by premedicating with an anticholinergic Headache Medications: Risk of Arrhythmia Risk of Torsades Possible Risk Unlikely to cause Risk if has de Pointes Torsades de Torsades de congenital Pointes Pointes long QT syndrome Chlorpromazine Fosphenytoin Amitriptyline Extensive list, all Domperidone* Lithiuum Citalopram in column 1 Droperidol Octreotide Clomipramine and 2 and Haloperidol Ondansetron Desipramine many from Methadone Quetiapine Doxepin column 3, and Pimozide Risperidone Fluoxetine many others Tizanidine Imipramine See: Venlafaxine Mexiletine www.torsades.org Ziprasidone Nortriptyline Paroxetine Protriptyline Sertraline Trimipramine Table adapted from Goodman & Gilman “Pharmacological Basis of therapeutics” Information from: www.torsades.org 2 10/16/2012 Therapy for acute refractory migraine Office, urgent care or emergency department (ED) • Approximately 50% of migraine patients are undiagnosed Emergency Department Treatment • More than 50% of migraine patients use OTC or simple analgesics; many use no treatment • Headache is the 4th most common reason to go to the ED (1.4‐3.3 million visits per annum) • More than 2/3rds are for a primary headache diagnosis Urgent Care: The Emergency Department Frequency of Medication Class Use Percentage of Patient Use • Not the usual headache: unusually severe or 80 70 prolonged 60 • Unusual symptoms such as new or prolonged 50 % 40 aura 30 • Ineffective usual treatment and backup 20 10 treatment 0 Dopamine Opioids NSAIDs Migraine Specific • Prolonged vomiting and dehydration Antagonists • No physician or no insurance Gupta,MX, Silberstein SD, Young WB, et al. Headache 2007;47:1125-1133. Evidence‐based Treatment for Refractory Comparative Sumatriptan Efficacy Migraine Medication Comparator % Pain % Pain Study Design • Few controlled, randomized studies of Relief Free Sumatriptan 6 mg Placebo 70 vs 35 31 vs 13 Akpunonu et al R/DB/P (1995) common drugs utilized in the ED SQ (p<.01) Sumatriptan 6 mg none 60 Miner et al Observational – (2007) Placebo arms rare SQ Sumatriptan 6 mg DHE 1 mg SQ 85 vs Winner et al R/DB – Use of combinations of medication complicate (1996) No difference at 3 hrs SQ comparison of single agents with each other (86 vs 90%) Sumatriptan 6 mg Chlorpromazine 12.5 mg 85 vs 73 42 vs 41 Kelly et al (1997) R All got SQ IV P=.002 metoclopromide 10 mg IV Sumatriptan 6 mg Metoclopromide 20 mg 70 vs 83 35 vs 59 Freidman et al R/DB (2005) With IV SQ IV diphenhydramine 25 mg Sumatriptan 6 mg Proclorperazine 10 mg 70 vs 96 Kostic et al R/DB (2010) With SQ IV diphenhydramine 12.5 mg SQ Adapted from Table 1. Kelley NE and Tepper DE. Headache 2012;52:114-128. 3 10/16/2012 Comparative DHE Efficacy Ketorolac (Toradol®) Medication Comparator % Pain Relief % Pain Study Design Free DHE 1 mg IV placebo 82 vs 20 Klapper and Stanton R/DB/P with • Usual dose 30 mg IV or 30‐60 mg IM (P<.002) (1991) metoclopromide 5‐10 mg IV DHE 1 mg IV Ketorolac 60 mg 78 vs 33 Klapper and Stanton R/DB with – Maximum use 3 consecutive days IV/5 days IM IM At 1 hour (P=.031) (1991) metoclopromide 5 mg IV DHE .5 mg IV Meperidine 75 86 vs 77 Scherl and Wilson R with • GI protection mg IM At 1 hour (1995) mettloclopromid e 10 mg IV/promethazine 25 mg IM DHE 1 mg IV Valproate 500 45 vs 50 Edwards et al (2001) R with • High risk for renal injury or GI bleed mg IV At 4 hours metoclopromide 10 mg IV DHE 1 mg IV Meperidine 75 38 vs 0 Belgrade et al (1989) R with • No concurrent steroids mg IM >90% pain reduction metoclopromide 10 mg IV/hydroxyzine 50 mg IM (P<.01) – Hold oral NSAIDs DHE 1 mg IV Meperidine 75 93 vs 21 Klapper and Stanton R/DB with mg IM (1993) metoclopromide 10 mg IV/hydroxyzine 75 mg IM DHE 1 mg IV Chlorpromazine 37 vs 80 (p<.05) 23 vs 33 Bell et al (1990) R/SB 12.5 mg IV Could be repeated once Adapted from Table 2. Kelley NE and Tepper DE. Headache 2012;52:114-128. Comparative Ketorolac (Toradol®) Efficacy Magnesium Sulfate Medication Comparator % Pain % Pain Free Study Study Design Relief Ketorolac 30 mg IV Proclorperazine 52 vs 68 Seim et al (1998) R/DB • 1‐2 grams IV every 12 hours 10 mg IV At 1 hr (P=.04) Ketorolac 30 mg IV Sumatriptan 6 64 vs 0 Jakubowski et al R/DB • Monitor reflexes with repeated dosing mg SQ At 2 hrs (P<.05) (2005) Delayed treatment after 4 hours Ketorolac 30 mg IM Meperidine 75 6 vs 30 Larkin and Prescott R/DB • If no side effects, may reach 1.5 times the mg IM At 1 hr (P<.05) (1992) Ketorolac 60 mg IM Meperidine 50 44 vs 60 Harden et al (1996) R/DB/P upper range of magnesium plasma level mg IM Placebo 55 With promethazine 25 mg IM • Contraindicated with renal insufficiency Ketorolac 60 mg IM Meperidine 100 24 vs 20 Duarte et al (1992) R/DB mg IM (P=.76) With hydroxyzine 50 mg IM • Side effects: brief flushing, diarrhea, mild Ketorolac 60 mg IM DHE 1 mg IV 33 vs 78 Klapper and Stanton R/DB At 1 hr (1991b) With metoclopromide 5 mg IV (P=.031) hypotension Ketorolac 60 mg IM Meperidine 75 50 vs 64 22 vs 21 Davis et al (1995) R/DB mg IM At 30 min At 30 min With promethazine 25 mg IM Adapted from Table 2. Kelley NE and Tepper DE. Headache 2012;52:467-482 Magnesium Efficacy Valproic acid (Depacon®) Efficacy Medication Comparator % Pain Relief % Pain Free Study Study Design Medication Comparator % Pain Relief Study Study Design Mg 1 gm IV Placebo (normal 100 vs 7 87 vs 7 Demirkaya et al R/SB/P saline) (P<.0001) (2001) 70% MA Valproate 500 DHE 1 mg IV with 50 vs 45 Edwards et al. R At 30 min mg IV Metoclopromide At 4 hours (2001) Mg 2 gm IV Placebo 15 vs 22 Corbo et al (2001) R/DB/P All with 10 mg IV metoclopromide 20 mg IV Valproate 500 Prochlorperazine 13 vs 86 Tanen et al R/DB Mg 2 gm IV Placebo 19 vs 24 Frank et al (2004) R/DB/P mg IV 10 mg IV (P<.01) (2003) Mg 1 gm IV Placebo 33 vs 17 MWA 23 vs 10 MWA Bigal et al (2002) R/DB/P Valproate 300 none 73 Mathew et al Observational 50 vs 13 MA (P<.05) 37 vs 7 MA mg IV In 30 min (2000) At 1 hour Mg 1 gm IV Placebo 47 vs 35 Cete et al (2004) R/DB/P Mg 2 gm IV Proclorperazine 10 56 vs 90 (P=.04) at 30 12 vs 40 Ginder et al (2000) R/DB/P mg IV min Mg 1 gm IV None 80 Mauskop et al Observational At 15 min (1996) Adapted from Table 2.