Treatment of Pediatric Migraine Headaches Liz Rende DNP, RN, CPNP-PC NAPNAP Pharmacology Update – April 28, 2017

Disclosures I have no financial disclosures to report

Off- Label Use Certain medications discussed are used off-label, without FDA approval Standard of practice If off-label, medications will be labeled as each is described

Objectives After attending this presentation, participants should be able to: Define appropriate three first-line treatments for episodic treatment of children’s migraine headaches Define appropriate three first-line treatments for prophylactic treatment of children’s migraine headaches Identify three key elements in the decision tree guiding the episodic, prophylactic, and/or ED management of children’s migraine headaches

Migraine Diagnostic Criteria & Prevalence International Classification of Headache Criteria-3 Beta Without Aura With Aura By age 3-7 years 7-11 years 15 years prevalence 1.2%-3.2% 4%-11% 8%-23% Gender ratio boys>girls boys=girls girls>boys 50-90% of relatives also have migraine Familial hemiplegic migraine L

“For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.”

Goals of Treatment Reduction of HA frequency, severity, duration, and disability Reduction of reliance on poorly tolerated, ineffective, or unwanted acute pharmacotherapies Improved QOL Avoidance of acute headache medication use (MOH) Education/promote self-management Reduction of headache-related distress and psychological symptoms

Treatment… Sooner is better…. School accommodations Treat immediately Have meds at school, with permission forms completed Communication

Andrew 7yo male Headaches at school- pale, nauseated Headaches happening about 1-2x/ month Ibuprofen 200mg – headache is gone in 2 hours

Episodic Treatment Treat No More Than 2x per Week Anti-Inflammatory effects OTCs Ketorolac Triptans Combination Products Midrin-APAP, dichloralphenazone, isometheptene Cafergot-Ergotamine and caffeine Bultalbital Antiemetics Prochlorperazine Promethazine Odansetron Lorazepam metaclopromide Treat No More Than 2x per Week

Episodic Treatment-OTC/NSAIDs Directed at inflammation of Trigemino-vascular system acetaminophen Dosing: 15mg/kg Age-4-16y Side Effects: hepatic failure Pearls-Limit dosing to 75mg/kg or 4G/day ibuprofen Dosing:7.5-10mg/kg Age:6-12y Side Effects: hives, dyspepsia, bleeding, renal impairment Pearls naproxen Dosing:10mg/kg Age:4-16y Side Effects: hives, dyspepsia, bleeding, renal impairment Pearls

Andrew Missed school 8yo male Headaches at school- pale, nauseated, vomiting at school Headaches happening about 1-2x/ month Ibuprofen 200mg – headache is a little better, but still has to come home due to vomiting Mom takes FMLA disability disability disability Missed school disability

Episodic Treatment- RX Triptans sumatriptan, rizatriptan, almotriptan, naratriptan, zolmitriptan, eletriptan, frovatriptan Mechanism of Action 5-HT (1) agonist-specific action on 5-HT 1B/1D receptors Indications- episodic migraine headache Dosing-nasal spray, ODT, tablet, injectable Side Effects- facial flushing, facial tingling, chest and throat tightness Contraindicated in: Moderate to severe asthma Cardiovascular disease Costly- MedicAid Pearls- chocolate Tootsie-Roll Give appropriate dose, not step-wise approach

FDA-Approved Triptans for Kids Almotriptan 12-17y Onset of action-60-180min Half-life-3hr Rizatriptan ODT 6-17y Onset of action:30-60min Half-life-2-2.5hr Zolmitriptan NS Onset of action:10-15min Half-life-2.5-3hr Sumatripan/naproxen combo Onset of action:60-240min Half-life-2/19hr Long-acting

Medication Overuse Headache Description: Headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days per month, depending on the medication) for more than three months. It usually, but not invariably, resolves after the overuse is stopped.

Andrew 11yo male Headaches at school- pale, nauseated Headaches happening about 6-7x/ month Rizatriptan 5mg resolves headaches within 2 hours. Missing school at least 1x/ month

Too many headaches? Two-armed approach Daily prophylactic medication Effective episodic, rescue/abortive medications

Headache Prophylactic Medications Level A Established Efficacy Level B Probably Effective Level C Possibly effective Level U Inadequate data Other ? Ineffective Not effective valproate amitriptyline nortriptyline gabapentin lamotrigine topiramate venlafaxine Llsinopril fluoxetine clonazepam metoprolol atenolol clonidine acetazolamide oxcarbazepine propranolol nadolol verapamil frovatriptan (menstrual migraine) cyproheptadine nicardipine ???Botox, Butterbur, magnesium, riboflavin, feverfew, tizanidine, pregabalin, zonisamide ???

Antihistamines Cyproheptadine (Periactin) Oldest kids HA treatment Mechanism- competes with histamine for H-1 receptor sites, serotonin antagonist SE-Drowsiness, weight gain Dosing-2-4mg 1-2X/day

Antidepressants-tricyclics nortriptyline or amitriptyline Nortriptyline-fewer side effects, costs less 50-60% effective Mechanism- inhibits norepinephrine and serotonin re-uptake SE-drowsiness, dry mouth Dosing-start at 10mg/day, increase to 30-50mg/day Contraindicated for anyone with arrhythmias, may prolong Q-T interval EKG? OFF-Label

Antidepressants-SSRIs Fluoxetine, paroxetine, sertraline HCL Not innocuous, taper must be slow Mechanism- Decreases serotonin re-uptake SE- drowsiness, weight gain Dosing-Start low, go slow Sertaline:25-50mg, paroxetine 25mg, Fluoxetine (liquid) BLACK BOX WARNING OFF-Label

Antihypertensives OFF-Label Beta blocker-propranolol, atenolol Mechanism-reduces vascular resistance, lowers B/P SE-Fatigue, sleep disturbances, depression, dizziness Dosing-max-1-2mg/kg/day Calcium channel blocker-verapamil Dosing-4-8mg/kg/day, divide in 3 doses OFF-Label

Anticonvulsants OFF-Label Depakote (Valproate Acid) Mechanisms: ?inhibits Ca+ channels; interacts with 5-HT; reduces neurogenic inflammation in peripheral TVS SE-Drowsiness, weight gain, hair loss, pancreatitis, thrombocytopenia, associated with neural tube defects Dosing-start at 10mg/kg/day Available as ER- 1x/day dosing Disadvantages-frequent blood levels, CBC, LFT’s OFF-Label

Anticonvulsants OFF-Label Topamax (topiramate) Mechanisms: blocks Ca+ channel and Na+ channels, carbonic anhydrase activity, enhances GABA effects ( inhibitory) SE-rash, acute angle glaucoma (rare- red eyes, eye pain, visual complaints), weight loss, word finding difficulties, cognitive and /or memory difficulties Dosing-Max 5-9mg/kg/ day, though typical dosing is 2-3mg/kg/ day Start at 15-25mg QHS; average is 100mg OFF-Label

Placebo Effect Preventive Pearls 60% 40% 30% 20% Even when they work, not guaranteed to get rid of all headaches Efficacy defined…… May take 4-8 weeks to notice effect “Two-fers” Meds do not take place of other interventions 20% 60% 40% 30% Placebo Effect

Andrew-Day 3 12yo male Headaches at school and at home- pale, nauseated Headaches happening about 3-4x/ month Amitriptyline 25mg QHS Has treated headache Day 1-rizatriptan and Zofran- minimal improvement Day 2-riatriptan, odantseron, diphenhydramine and naproxen Headache still present; unable to go to school

What do I do (next…..) OTC medications Prescribed medications Combined “cocktails”

Acute Treatment at Home The “Headache Cocktail” Triptan, antiemetic, OTC Add-on medications diphenhydramine Mg+ Co-Enzyme Q-10 Vitamin B2 Migralief Butterbur-SE

Acute Migraine Treatment in ED Acute Treatment at ED Acute Migraine Treatment in ED Sumitriptan 4-6mg SQ Antiemetics + DHE 0.5-1mg IV Prochlorperazine Metoclopramide 20mg IV Ketorolac 30mg-60mg IM Magnesium 1-2GM IV Valproate 300-500mg IV Corticosteroids –dexamethasone 10-24mg IV) 0.9 % Saline bolus with: Ketorolac 0.5mg/kg (max 30 mg) IV prochlorperazine 0.15mg/kg IV (max 30mg) +/- dexamethasone +/- magnesium infusion Valproate 15-20mg/kg Dihydroergotamine (DHE) intranasal /iv Oxytocin ? Lack of controlled trials

Special situations Asthma Cardiovascular disease Sickle Cell disease Connective tissue disease: Marfans’; Loeys-Dietz Menstrual-related migraine Status Migrainosus

Opioids?

Take a Massage and Call Me in the Morning Complementary & Alternative Therapies Take a Massage and Call Me in the Morning Non-Drug therapies ***FLUIDS*** Dietary Interventions Headache Diary Environmental Adjustments Herbal/Vitamin Therapies Acupuncture/Acupressure Biofeedback Aromatherapy Chiropractic manipulations

“For prevention, it is essential to prescribe a sound rhythm in life, for work and rest, mealtimes, and sleep.”Dr. Bo Bille THE END