Prevention and Treatment of Migraines CAITLIN BARNES, PHARM.D. CANDIDATE AMBULATORY CARE JOE CAMMILLERI, PHARM.D. NATOHYA MALLORY, PHARM.D.

Prevention and Treatment of Migraines CAITLIN BARNES, PHARM.D. CANDIDATE AMBULATORY CARE JOE CAMMILLERI, PHARM.D. NATOHYA MALLORY, PHARM.D.

Objectives Present patient case Review epidemiology/pathophysiology of headaches Assess and evaluate treatment options Assess and evaluate prophylaxis management Review primary literature Revisit patient case

Patient Case 69 y/o AAF CC: frequent headaches, pain on both sides of the neck, nausea/vomiting PMH: classic migraine with aura, DM, DPN, GERD, HTN, HLD, low back pain, OSA, asthma

Patient Case Vitals BP 159/71, HR 69, RR 16 Labs Na 139 meq/l Glu 111 mg/ dl K 3.5 meq/l BUN 8 mg/ dl Cl 104 meq/ L CO 2 27 meq/l SCr 0.72 mg/dl Mg 2.1 mg/ dl Phos 3.8 mg/dl WBC 5.7 x 10 3 /mm 3 Hg 11.6 g/dl Hct 36.7% Plt 232 x 10 3 /mm 3 Medications Amlodipine 10 mg daily Baclofen 10 mg QHS Carvedilol 6.25 mg BID Fluticasone 50 mcg 2 sprays in each nostril daily Fluticasone/Salmeterol 500-50 1 puff BID Gabapentin 300 mg TID HCTZ 25 mg daily Lisinopril 40 mg BID Metformin 1,000 mg BID Omeprazole 40 mg daily Pravastatin 40 mg QHS ProAir 108 mcg 2 puffs q6h prn Montelukast 10 mg daily Tramadol 50 mg TID prn

Epidemiology and Pathophysiology Most prevalent neurological disorders Episodic instability of the neurovascular system Available 5-HT might be diminished Trigeminal nerve becomes hyperactive

Types of Headaches Primary headaches Migraine (with or without aura) Tension-type Cluster Secondary headaches Head and/or neck trauma Cranial or cervical vascular disorder Non-vascular intracranial disorder Substance or its withdrawal Infection Disorder of homeostasis Pyschiatric disorder

Migraines With aura Fully reversible aura symptoms Attacks last 4-72 hours Unilateral location Pulsating quality Moderate-severe intensity Aggravation by routine physical activity Associated with nausea/vomiting and/or photophobia or phonophobia

Treatment Goals Reduce attack frequency, severity, and disability Improve quality of life Educate and enable patients to manage their disease to enhance personal control of their migraine Reduce headache-related distress and physiological symptoms

Migraine Treatment Institute for Clinical Systems Improvement. Diagnosis and Treatment of Headache, 11 th edition. 2013

Migraine Treatment Treatment APAP NSAIDs Ergot derivatives Triptans Prophylaxis Beta-blockers Anticonvulsants Antidepressants

Mild to Moderate Treatment -- Analgesics Acetaminophen Caution in renal/hepatic impairment Stevens-Johnson Syndrome & toxic epidermal necrolysis NSAIDs Caution in patients with a history of ulcers & GI bleeds

Moderate Treatment -- Ergot Derivatives MOA: inhibits reuptake of NE & stimulates α receptors causing increased vasoconstriction Use is limited Renal/hepatic contraindicated Pregnancy - contraindicated

Triptans Mild to severe MOA-A elimination (sumatriptan, zolmitriptan, rizatriptan, almotriptan) Renal elimination (naratriptan) CYP 1A2/3A4 (frovatriptan, eletriptan) Interactions Serotonin syndrome

Migraine Prophylaxis -- Beta-Blockers Metoprolol, propranolol, timolol Selection based on patient specifics Hepatic impairment

Migraine Prophylaxis -- Anticonvulsants Valproate Contraindicated in hepatic impairment Category X Pancreatitis Topiramate Nephrolithiasis Oligohydrosis Caution in renal/hepatic impairment

Migraine Prophylaxis -- Antidepressants TCA s Anticholinergic effects Caution in hepatic impairment/elderly SNRI s Nausea Take in the AM Monitor changes in blood pressure Caution in hepatic impairment

Meta-Analysis of Oral Triptan Therapy Randomized, double-blind, placebo-controlled trials Outcome: Percentage of patients who were pain free within 2 hours Results: Rivatriptan 10 mg & zolmitriptan 5 mg were the most clinically effective

Amitriptyline vs. Divalproate in Migraine Prophylaxis Randomized, prospective Outcome: more than 50% reduction in headache frequency & one or more grade reduction in severity Results: divalproate had more significant reductions by 3 months, no difference at 6 months

Patient Case 69 y/o female diagnosed with migraines with aura Recommendation Initiate divalproex 250 mg BID and titrate dose Reassess in 6-12 months

References 1. Headache Classification Committee of the International Headache Society. The International Classification of headache Disorders, 3 rd edition. Cephalgia. 2013. 33;(9):629-808. 2. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Headache, 11 th edition. 2013. Available from: www.icsi.org. 3. National Institute for Health and Clinical Excellence. Diagnosis and management of headaches in young people and adults. 2012. Available from: www.nice.org.uk. 4. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison With Other Recent Clinical Practice Guidelines. Headache. 2012. 52:930-945. 5. Tfelt-Hansen P, De Vries P, Saxena P. Triptans in Migraine. Drugs. 2000. 60;(6): 1259-1287. 6. Adelman J, Belsey J. Meta-analysis of Oral Triptan Therapy for Migraine: Number Needed to Treat and Relative Cost to Achieve Relief Within 2 hours. Journal of Managed Care Pharmacy. 2003. 9(1):45-52. 7. Rolan P. Drug Interactions with Triptans. CNS Drugs. 2012. 26:949-957. 8. Kalita J, Bhoi SK, Misra UK. Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial. Acta Neurol Scand. 2013. 128:65-72.

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