PGY2MS CommunityBased Pharmacy Administration Resident The Ohio State University College of Pharmacy Kroger Health Session Objectives Review etiology and pathophysiology of primary headaches migraine tensiontype cluster ID: 1047417
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1. Headache TherapeuticsMax Conrad, PharmDPGY2/MS Community-Based Pharmacy Administration ResidentThe Ohio State University College of Pharmacy, Kroger Health
2. Session ObjectivesReview etiology and pathophysiology of primary headaches (migraine, tension-type, cluster)Identify classification and patient presentation for different primary headachesEvaluate pharmacologic and non-pharmacologic treatment strategies for primary headachesApply clinical pearls for treatment of primary headaches
3. Primary Headaches
4. Epidemiology of MigraineComorbid conditions commonMore common in females than malesMore common in younger patients~90% of patients have FH of migraine
5. Migraine PathophysiologyNeuronal etiology: Depressed neuronal electrical activity spreads across the brain, which produces transitory neuronal dysfunction Changes in HomeostasisVasodilation of vessels in response to meningeal activationCompensatory overactivity in the trigeminovascular system of the brain Trigeminal nerve sends nociceptive stimuli via various pathways Brain stemSensory regions (olfactory, ophthalmic, somatosensory)Takeaway: Changes in neuronal pathways cause pain
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8. Migraine Headache – Diagnosis
9. Migraine Headache – Clinical PearlsKnow what migraines look likeTo treat or refer? REFERProper treatment = better daily functionMigraines often managed by PCPTwo avenues of pharmacologic management:Abortive treatmentPrevention
10. Migraine Headache – Non-Pharmacologic Treatment
11. Migraine Abortive Treatment – First-Line TherapiesNSAIDs TriptansOTC AgentsDiclofenacIbuprofenNaproxenSumatriptan RizatriptanNaratriptan FrovatriptanZolmitriptan Eletriptan AlmotriptanAcetaminophenAPAP/aspirin/ caffeine
12. Migraine Abortive Treatment – NSAIDsNSAIDsIbuprofenNaproxenDiclofenacTreatment of choice for mild-moderate acute migrainePain relief: equally effectiveAvoid in: CVD (inc. CV events), past hx of GI ulcersSide effects: GI irritation (BBW), abdominal cramps, bloating Treatment strategy: Treat until migraine subsides, avoid medication overuseMonitoring: GI sx, treatment duration
13. Migraine Therapeutics – NSAID dosing DrugDoseUsual Range/CommentsIbuprofen (Motrin)400-800 mg every 6 hoursAvoid doses >2.4 g/dayNaproxen sodium (Aleve, Anaprox)550-825 mg at onset; can repeat 220 mg in 3-4 hoursAvoid doses >1.375 g/dayDiclofenac (Cataflam, Voltaren)50-100 mg at onset; can repeat 50 mg in 8 hoursAvoid doses >150 mg/day
14. Migraine Abortive Treatment – TriptansTreatment of choice for moderate-severe acute migraineVariety of dosage forms Onset: SubQ > NS > ODT > OT Avoid in: Ischemic Heart Disease (IHD), uncontrolled HTN, pregnancySide effects: Paresthesia, fatigue, dizziness, flushing, ‘triptan sensation’, specific to route of admin. Treatment strategy: Choose based on PK, specifics of headache, hx of triptan useDDIs: CYP3A4 inhibitors (Eletriptan), SSRI/SNRI (serotonin syndrome)Monitoring: efficacy, freq. of use TriptansSumatriptan RizatriptanNaratriptan FrovatriptanZolmitriptan Eletriptan Almotriptan
15. DrugHalf-Life (hours)Time to Maximal Concentration (tmax)Almotriptan (Axert)3-41.4-3.8 hoursEletriptan (Relpax)4-51-2 hoursFrovatriptan (Frova)252-4 hoursNaratriptan (Amerge)5-62-3 hoursZolmitriptan (Zomig, Zomig-ZMT)3Oral2 hoursDisintegrating3.3 hoursNasal4 hoursSumatriptan (Imitrex)2SC injection12-15 minutesOral tablets2.5 hoursNasal spray1-2.5 hoursRizatriptan (Maxalt, Maxalt-MLT)2-3Oral tablets1-1.2 hoursDisintegrating1.6-2.5 hours
16. Naratriptan (Amerge)1 or 2.5 mg; can repeat after 4 hoursOptimal dose - 2.5 mg; MDD - 5 mgRizatriptan (Maxalt, Maxalt-MLT)5 or 10 mg as OT or ODT; can repeat after 2 hoursOptimal dose - 10 mg; MDD - 30 mg; Almotriptan (Axert)6.25 or 12.5 mg; can repeat after 2 hoursOptimal dose - 12.5 mg; MDD - 25 mgFrovatriptan (Frova)2.5 or 5 mg; can repeat in 2 hoursOptimal dose - 2.5-5 mg; MDD - 7.5 mg (3 tablets)Eletriptan (Relpax)20 or 40 mg; can repeat after 2 hoursMaximum single dose - 40 mg; MDD - 80 mgDrugDoseUsual Range/CommentsSumatriptana (Imitrex)Injection6 mg subcutaneous; can repeat after 1 hourMDD - 12 mgOral tablets25, 50, 85, or 100 mg; can repeat after 2 hoursOptimal dose - 50-100 mg; MDD - 200 mg; combination product with naproxen, 85/500 mg (Treximet)Nasal spray5, 10, or 20 mg; can repeat after 2 hoursOptimal dose - 20 mg; MDD - 40 mgZolmitriptana (Zomig, Zomig-ZMT)Oral tablets2.5 or 5 mg as OT or ODT; can repeat after 2 hoursOptimal dose - 2.5 mg; MDD - 10 mgDo not divide ODT dosage formNasal spray5 mg (one spray); can repeat after 2 hoursMDD - 10 mg
17. Migraine Abortive Treatment – OTC AgentsEffective for mild-moderate migraine headacheAPAP: Less effective, less side effects than NSAIDsAPAP/aspirin/caffeine: Combination approved for treatment of migraine and symptomsSide effects: minimal, well toleratedMonitoring: max doses, freq. of use, medication reconciliationOTC AgentsAcetaminophenAPAP/aspirin/ caffeine
18. Migraine Treatment – OTC DosingDrugDoseCommentsAcetaminophen (Tylenol)1,000 mg at onset; repeat every 4-6 hours as neededMaximum daily dose is 4 gAcetaminophen 250 mg/aspirin 250 mg/caffeine 65 mg (Excedrin Migraine)2 tablets at onset and every 6 hours
19. Migraine Prevention – First-Line TherapiesBeta-BlockersAnticonvulsantsTriptans (for MRM*)PropranololMetoprololTimololDivalproexTopiramateFrovatriptanMigraine Prevention – Second-Line Treatments AntidepressantsTriptansAmitriptyline VenlafaxineNaratriptanZolmitriptan
20. Migraine Prevention – Beta-Blockers Beta-BlockersPropranololMetoprololTimololMost commonly used drug class for preventionIdeal patient: Migraine with comorbid HTN, angina, IHD Avoid in: asthma, COPD, bradycardia Side effects: Fatigue, lethargy, bradycardia, hypotension, erectile dysfunction Treatment strategy: Start low, go slowMonitoring: BP, HR
21. Migraine Prevention – Anticonvulsants Ideal patient: Migraine with comorbid seizure disorder (Divalproex – Bipolar)DivalproexAvoid in: hCG+, liver disease Side effects: GI, somnolence, vomiting, nauseaTreatment strategy: Start low, monitor VPA levels if nonadherentTopiramateAvoid in: hCG+, kidney stones, liver diseaseSide effects: paresthesia, fatigue, kidney stonesTreatment strategy: start low, increase weekly to optimal doseAnticonvulsantsDivalproexTopiramate
22. Migraine Prevention – Frovatriptan Ideal patient: Menstrual-Associated MigraineLong-half life – ideal for prophylaxisRefer to triptan content for further therapeutics infoTriptans (for MRM*)Frovatriptan
23. Migraine Prevention – Antidepressants Less data to support use in migraine preventionIdeal patient: Migraine with comorbid depression, anxiety, insomniaAmitriptylineAvoid in: BPH, cardiac disease, seizure hxSide effects: sedation, anticholinergic effects, cardiac abnormalitiesTreatment strategy: Start low at bedtime, inc. to depression resolutionVenlafaxine Avoid in: uncontrolled HTNSide effects: Nausea/vomitingTreatment strategy: start low, d/c slow AntidepressantsAmitriptyline Venlafaxine
24. Migraine Treatment – CGRP AntagonistsOnce monthly injection for prevention of migraineErenumab (Aimovig) Fremanezumab (Ajovy)Galcanezumab (Emgality) As needed for the treatment of migraineRimegepant (Nurtec) Ubrogepant (Ubrelvy) Key takeaways:Expensive; many require prior authorizationGood option for refractory migraine patients
25. Summary – Migraine Headache Every patient is different – patient assessment is important!Pharmacologic interventions for treatment and preventionAbortive treatment: minimum dose for minimum duration; avoid overusePrevention: Focus of comorbidities to guide therapyNewer agents: expensive, may require step therapy/PA
26. Tension-Type Headache (TTH)Most common type of headachePathophysiology not well-defined Tends to be defined by what it is notSymptoms of TTH:Bilateral headache Chronic or episodic Tight band around the head Waxes and wanes is severity No aggravation by physical activities No nausea Photophobia and phonophobia may occur
27. Tension-Type Headache (TTH) Classification
28. TTH DiagnosisDuration of headache (30 minutes to 7 hours)2 of the following 4 characteristics: bilateral locationpressing or tightening (non-pulsating) qualitymild or moderate intensitynot aggravated by routine physical activityBoth of the following:no nausea or vomitingno more than one of photophobia or phonophobiaNot better accounted for with any other diagnosis The International Classification of Headache Disorders – Tension-Type Headache, 3rd edition beta version. Cephalalgia 2013; 33: 629-808.
29. Tension-Type Headache – Clinical PearlsTo treat or refer? TREATOften treated OTC, without provider supportAssess patient preferences to guide therapyNon-prescription products – mainstay of therapyCan use prophylaxis if approaching med overuse for treatmentAmitriptyline – best evidenceMinimum dose, minimum durationCombination agents - < 10 days/monthNSAIDs/APAP - < 15 days/month
30. TTH Treatment – Non-Pharmacologic Options
31. TTH Treatment – First-Line TherapiesNSAIDsCombination agentsNon-Pharmacologic OptionsIbuprofenNaproxenDiclofenacAPAP/aspirin/ caffeineAcetaminophenCBT Stress ManagementBiofeedback
32. Medications to Avoid – Migraine and TTHEngagement Point: What are some reasons why you would recommend against these agents? (Please provide at least two)
33. Cluster Headache – BackgroundMost painful primary headacheLess common than migraine, TTH (affects 0.12% of the population)More common in men (ration of 4:1)85% of patients with cluster headaches currently smoke or have hx of smokingPathophysiology unknownThought to originate in the hypothalamus Activates autonomic cranial reflexes
34. Cluster Headache – Diagnosis & ClassificationAt least 5 attacks fulfilling criteria B-D Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 min (when untreated)Either or both of the following:1 of the following ipsilateral symptoms or signs:Conjunctival injection and/or lacrimationNasal congestion and/or rhinorrhoea Eyelid oedema Forehead and facial sweating Forehead and facial flushing; Sensation of fullness in the ear Miosis and/or ptosis A sense of restlessness or agitation Frequency from 1-2/d to 8/d for > half the time when active Not better accounted for with any other diagnosis The International Classification of Headache Disorders – Cluster Headache, 3rd edition beta version. Cephalalgia 2013; 33: 629-808.
35. Cluster Headache – Clinical PearlsTo treat or refer? REFERLook for the frequency, rhythm of attacksCan occur daily for weeks to months, followed by HA-free periodsListen for key wordsExcruciatingDrillingBehind, between the eyesTwo avenues of pharmacologic management:Treatment Prevention
36. Cluster Headache – Acute Treatment Options
37. Cluster Headache – Prevention Options
38. Session ObjectivesReview etiology and pathophysiology of primary headaches (migraine, tension-type, cluster)Identify classification and patient presentation for different primary headachesEvaluate pharmacologic and non-pharmacologic treatment strategies for primary headachesApply clinical pearls for treatment of primary headaches
39. References Harrell T, Minor DS. Harrell T, & Minor D.S. Harrell, T. Kristopher, and Deborah S. Minor. Headache Disorders. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.),Eds. Joseph T. DiPiro, et al.eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020. Accessed September 23, 2021. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=2577§ionid=224358352Ha H, Gonzalez A. Migraine headache prophylaxis. Am Fam Physician. 2019;99(1):17-24.Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J, Diener H-C. Acute migraine headache. Neurology. 2002;58(8):1234-1238. doi:10.1212/wnl.58.8.1234Nestoriuc Y, Rief W, Martin A. Meta-Analysis of Biofeedback for Tension-Type Headache: Efficacy, Specificity, and Treatment Moderators. J Consult Clin Psychol. 2008;76(3):379-396. doi:10.1037/0022-006X.76.3.379Harris P, Loveman E, Clegg A, Easton S, Berry N. Systematic review of cognitive behavioural therapy for the management of headaches and migraines in adults. Br J Pain. 2015;9(4):213-224. doi:10.1177/2049463715578291The International Classification of Headache Disorders, 3rd edition beta version. Cephalalgia 2013; 33: 629-808. Cleveland Clinic. Migraine Headaches. Last Reviewed 3 March 2021. Last Accessed 8/23/21. https://my.clevelandclinic.org/health/diseases/5005-migraine-headaches