Headache Disorders (21-22) PDF

HEADACHE DISORDERS Sher if Mahmoud, B S c ( P h a r m ) , M S c , P h D, F N C S C l i n i c a l P ro f e s s o r a n d A s s o c i a t e D e a n , A c a d e m i c Fa c u l t y o f P h a r m a c y a n d P h a r m a c e u t i c a l S c i e n c e s Copyrighted material contained...

HEADACHE DISORDERS Sher if Mahmoud, B S c ( P h a r m ) , M S c , P h D, F N C S C l i n i c a l P ro f e s s o r a n d A s s o c i a t e D e a n , A c a d e m i c Fa c u l t y o f P h a r m a c y a n d P h a r m a c e u t i c a l S c i e n c e s Copyrighted material contained herein is reproduced under ss. 29- U n ive r s i t y o f A l b e r t a 29.4 of the Canadian Copyright [email protected] Act. This document is available for your individual use; further distribution may infringe copyright  OBJECTIVES Students will be able to: Describe the classification of headache disorders Describe the epidemiology of headache disorders Describe the assessment and diagnostic criteria for headache disorders Describe the management of headache disorders Discuss the role of the pharmacist in managing and monitoring headache disorders  OUTLINE Definition Classification of headache disorders Primary headache disorders Epidemiology Classification Onset Diagnostic Criteria Assessment Management Non-pharmacological Pharmacological Medication overuse headache Special populations Monitoring  REQUIRED READING Sherif H Mahmoud (2019) Headache (Chapter 4). In: Mahmoud S. (eds) Patient Assessment in Clinical Pharmacy. Springer, Cham https://link.springer.com/book/10.1007%2F978-3-030- 11775-7  SCENARIO 1 Adam 47 M presented to your pharmacy complaining of headache What are your next steps? Use SCHOLARE inintensity infrequency Pain intensity SgtMandela Onset - is it new or ongoing Red flags Med changes recently Hydration.. worst headache of precipitating factors Comorbidities my life Location in the head - unilateral, bilateral send to ER hematom  DEFINITION “Pain in the head” Headache is one of the most common complaints encountered by healthcare practitioners  THE INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICHD-III) Primary Headaches headache w no apparentcause Migraine Tension-type headache Trigeminal autonomic cephalalgias (including cluster headache) Other primary headaches Painful cranial neuropathies, other facial pains and other headaches Cranial neuralgias and central causes of facial pain Other headaches Cephalalgia, 2018; 38(1): 1-211  THE INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICHD-III) Secondary Headaches treatmentusuallyinclude treatingunderlyingcause As a symptom of organic disease Head and neck trauma Cranial or cervical vascular disorders Non-vascular intracranial disorders Substance or its withdrawal Infection covid flu Disorders of Homeostasis hypotension thyroidchanges hypertension Gone Facial pain due to disorders of the cranium, neck, toothe nose, eye, ear, sinuses, mouth or teeth Psychiatric disorders mosteverysinglemed includingheadachemeds Eggs Cephalalgia, 2018; 38(1): 1-211 PRIMARY HEADACHES  TENSION-TYPE HEADACHE (TTH) Epidemiology Experienced, with at least one attack in a life-time, by 90 % of all females and 70% of all males Classification Episodic infrequent TTH: 6 months may need prophylaxis  TENSION-TYPE HEADACHE (TTH) Onset May occur at any age but less common in those who are over 50 Can be precipitated by mental stress and tension, smoking, fatigue, prolonged poor body posture e.g. excessive computer use  TENSION-TYPE HEADACHE (TTH) Diagnostic Criteria A. Episodes fulfilling criteria B-D. The frequency of the episodes determine the TTH class. B. Headache lasting from 30 min – 7 days C. Headache has at least 2 of the following characteristics: Bilateral location Pressing/tightening (non-pulsating) quality Mild or moderate intensity Not aggravated by routine physical activity such as walking or climbing 1 stairs D. Both of the following: No nausea or vomiting (anorexia may occur) No more than one of photophobia or phonophobia E. Not attributed to another disorder International Headache Society Classification ICHD-III https://www.ichd-3.org/  MIGRAINE Epidemiology ~15-18% in females and 5-8% in males. ~3.5 million Canadians experienced migraine Strong family history relevance Ranked by WHO as one of the top 20 conditions causing disability Classification With aura (Classic Migraines) - 25% Without aura (Common Migraines) - 75% Onset Onset is always below the age of 50  MIGRAINE TRIGGERS Stress Smoking Fatigue Altered sleep patterns Some medications Weather changes Menses Odors Caffeine withdrawal Some food such as cheese, wine, chocolate, MSG and hot dogs food w MSG monosodiumglutamate any  sometimes pt starts taking migrainemedbeforemigraine WHAT IS AURA? even starts A sensory perception that precedes a migraine attack It involves visual or sensory perceptions e.g. flashing lights, geometric patterns, distorted vision or hearing sounds Aura may last 5-60 min, and headache will follow within an hour  MIGRAINE FYI only Diagnostic Criteria – Migraine without Aura A. At least 5 attacks fulfilling criteria B-D B. Headache lasting from 4 – 72 h (untreated or successfully treated) C. Headache has at least 2 of the following characteristics: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (e.g. walking, climbing stairs) D. During headache at least one of the following: Nausea and/or vomiting Photophobia and phonophobia E. Not attributed to another disorder International Headache Society Classification ICHD-III https://www.ichd-3.org/  MIGRAINE Diagnostic Criteria – Migraine with Aura A. At least 2 attacks fulfilling criteria B-D B. Aura consisting of visual, sensory and/or speech/language symptoms, each fully reversible, but no motor, brainstem or retinal symptoms C. At least 2 of the following characteristics: more symptoms occur in succession Each individual aura symptom lasts 5-60 min At least one aura symptom is unilateral The aura is accompanied, or followed within 60 min, by headache D. Headache fulfilling criteria B-D for migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder International Headache Society Classification ICHD-III https://www.ichd-3.org/  able fig CLUSTER HEADACHE Epidemiology The most severe of primary headache disorders A rare condition (0.1% incidence) More predominant in males than females (reported 4:1 to 12:1) Classification 10 15 min headacheattacks 10 or so headachesin aday Episodic CH: cluster attacks with remission in between (80-85%) Chronic CH: cluster attacks with no significant remission (15-20%)  CLUSTER HEADACHE Onset Occurs at any age – most common onset 20-40 years Nitroglycerin, phosopdiesterase-5 inhibitors, alcohol and strong smells may precipitate the attack unilateral trigeminalautonom cephalgia  CLUSTER HEADACHE Diagnostic Criteria A. At least 5 attacks fulfilling criteria B-D B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated C. Headache is accompanied by at least 1 of the following: takemedsbefore headache starts Ipsilateral conjunctival injection and/or lacrimation be absorptionat if Ipsilateral nasal congestion and/or rhinorrhea severepain Ipsilateral eyelid edema tensinis Geration Ipsilateral forehead and facial sweating Ipsilateral miosis and/or ptosis A sense of restlessness or agitation D. Attacks have a frequency from 1 every other day to 8 per day E. Not attributed to another disorder cluster International Headache Society Classification ICHD-III https://www.ichd-3.org/ CONTRAST OF PRIMARY HEADACHE DISORDERS  ASSESSMENT OF HEADACHE Medical history Headache history – (SCHOLAR or SCHOLAR-E) Headache diary Age of onset, frequency, duration, severity, location Associated symptoms Precipitating, aggravating and relieving factors Important to determine the presence of red flags Physical examination Normal physical examination is expected, otherwise thorough investigation will be needed e.g. CT-scan, lumber puncture, lab tests Dental examination tooth ache headache Dental pain, bruxism Laboratory and imaging  RED FLAGS new Onset: ages > 50 or < 5 years Severe and abrupt onset of headache “Thunderclap” severe ofmylife headache Increased frequency or increased severity Significant change in pattern (atypical) Other signs such as stiff neck, reduced consciousness, fever, sick appearance New onset in pregnancy eclampsia pre eclampsia WHAT SHOULD YOU DO? Refer MANAGEMENT Headache Disorders  SCENARIO 2 Mona, a 24-year-old woman, suffers from migraines. Her migraine attacks are so severe that they force her to halt any physical activities. She experiences these attacks approximately 10 days per month. What are the therapy goals? frequencyofmigraine improvequalityoflife intense rise  GOALS OF THERAPY Symptomatic treatment of headache and associated symptoms e.g. N, V Prevent recurrence of headache Treat the secondary causes of headache Prevent complications and adverse effects of drug therapy NON-PHARMACOLOGICAL TREATMENT Patient education about their headache, available treatments and the expected results Patient reassurance Avoid triggers (especially in migraine) e.g. stress, some kinds of food, poor sleep habits, smoking Ice pack, maintain adequate sleep pattern, rest in a dark, quiet room NON-PHARMACOLOGICAL TREATMENT Informal psychotherapy Biofeedback Relaxation therapy Cognitive-behavioral therapy Acupuncture  SCENARIO 3 Donna (54 F) has TTH. Other secondary causes of headache were excluded. Frequency of attacks ~3 days per month Recommend an appropriate abortive therapy for her Does she require headache prophylaxis? PHARMACOLOGICAL TREATMENT – GENERAL PRINCIPLES Acute headache: Start treatment as soon as possible Use the minimum recommended dose, then titrate Choose an agent case by case: How severe is the attack? Are there any associated symptoms? Was a specific treatment effective in previous attacks? Check for medical history and any contraindications Patient preference  PHARMACOLOGICAL TREATMENT – GENERAL PRINCIPLES Consider prophylaxis when: Frequent attacks – use of analgesics >15 days/month or 2 days/week Severe disabling attacks Short-lived especially with cluster headache Principles of prophylaxis: Initiate low and go slow Use long acting medications to improve adherence If patient is attack free for 6-12 month, consider tapering the dose  TENSION-TYPE HEADACHE knowdoses NSAIDS and Sumatriptan Treated with analgesics: NSAIDs, most commonly ibuprofen (200-600 mg), ASA (325-975 mg) and naproxen (250-500 mg) Caffeine combination with analgesics (2 nd line) Acetaminophen (500 -1000 mg) with or without codeine Codeine combination use should be avoided for TTH and should be limited because of the increased risk of dependency and MOH (< 10 days/month) metietianeuse Analgesic use should be limited to not more than 15 days per month to avoid medication overuse headache (MOH) DO TTH PATIENTS NEED PROPHYLAXIS? Generally, they do not need prophylaxis because of the mild to moderate nature of TTH and its short duration; however; prophylaxis will be considered if: The attacks are severe enough to limit the usual daily activity of the patient Headache is frequent (>2-3 attacks per week) Analgesics are contraindicated Analgesics are ineffective or overused  TTH PROPHYLAXIS OPTIONS Tricyclic Antidepressants (TCAs) e.g. amitriptyline 30-75 mg qHS Most commonly used in TTH prophylaxis Titrate the dose till giving the effect – response is usually in 2-3 weeks Common side effects: anticholinergic effects (dry mouth, blurred vision), orthostatic hypotension Other options Venlafaxine Mirtazapine MIGRAINE Management  SCENARIO 4 Red flag Ed (74 M) has developed new-onset migraines. He came to your pharmacy with a complaint of headaches What would be an appropriate abortive therapy for his migraines?  SCENARIO 5 Emily (44 F) has migraine. Other secondary causes excluded. Frequency of attacks ~3 days per month What would be an appropriate abortive therapy for her? Stratified Care vs Stepped Care  ifsevere 9EEa'nsTdita TsE5 Ashina et al. Migraine: integrated approaches to clinical management and emerging treatments. The Lancet. 2021 Mar 25.  PHARMACOLOGICAL ALTERNATIVES FOR ACUTE MIGRAINE First-line Second-line NSAIDs Acetaminophen Triptans Third-line ASA secondlinebcof Fourth-line sideeffectprofile Triptans + NSAIDS sumatriptan naproxen Ergot vasoconstrictive very combo effective derivatives Gepants usea Éstigains continuousmigraine Ditans  ANALGESICS formigraine tohelpw nauseaor to absorption Acetaminophen 1000 mg ± metoclopramide 10 mg ASA 975 mg ± metoclopramide 10 mg Ibuprofen 400-600 mg Naproxen 500 mg Diclofenac 50 mg Ketorolac 30-60 mg IM injection (max 120 mg/d) It may be tried if other agents failed to control the acute attack onlyimectable NSAID usedinhospital Limit their use to less than 15 days per month to avoid MOH Contraindications? Jam Ads EEers  neurogenic inflammation TRIPTANS vasoconstrictive serotonin agonist useqontainmaeastttttfo.it tos Indications In moderate to severe migraine headache When analgesics and NSAIDs are ineffective When analgesics are used frequently  Do notuse a triptan w i 24hr of anothertriptan TRIPTANS bc of vasoconstriction risk vasoconstrictive Adverse effects Fatigue, dizziness, drowsiness Paresthesia Nausea, abdominal pain Chest discomfort chesttightness Contraindications Absolute Ischemic heart disease or any cardiac or cardiac-like symptoms Stroke or TIA Peripheral vascular disease such as ischemic bowel disease Basilar or hemiplegic migraine Imptoms mimicstroke bothassociatedw a riskofstroke Relative Uncontrolled hypertension Pregnancy or breastfeeding sumatriptanmightbeok Smoking  nomorethan 15daysmonth tristonsnomorethan todays month TRIPTANS Do not use a triptan within 24 h after another triptan or ergot (additive vasoconstriction) There is no benefit of giving another dose if the given triptan is ineffective but you can try another one Use less than 10 days/month to avoid MOH inns Use with caution when co-administered with SSRIs and tristans a SNRIs due to the increased risk of “serotonin syndrome”. E.ee s Avoid: not anabsolute CI triptans are Prnuse Co-administration with ergot derivatives Co-administration with MAO inhibitors some triptans are metabolizedby MAOenzyme except eggiiig.in notants s  TRIPTANS Seven triptans are available All have demonstrated efficacy Minor differences among them Which one to choose? patient preference sideeffects Route  TRIPTANS Patient preference is the major guidance of choice Adverse effects tolerability Efficacy Convenient dosing Dosage form preference Cost/drug coverage And.. the minor differences Do not memorize mend dose except Sumatriptan 9st sept sister POL SQ TRIPTANS song goodstartdose 100mg goodefficacybut chanceAE knowthedifferences bw them 200mg 24h max Sumatriptan (Imitrex®) Naratriptan (Amerge®) Oral: 25–100 mg; may repeat in 2 h; Oral: 1– 2.5 mg ; may repeat in 4 h; max. 200 mg/24 h max. 5 mg/24 h delayed onset of effects SC: 6 mg sc; may repeat in 1 h; max. close to placebo side effects 2 injections/24 h T.at imiiIneacame Nasal spray: 5–20 mg may repeat in 2 h; max. 40 mg/24 h Onset: SC>Inhalation>oral The slowest onset triptan SC route is very effective for Minimal side effects severe migraine and acute Less HA recurrence rate (may cluster headache consider in patients with high recurrence rates) Best for patients who can’t tolerate the SE of other triptans.  TRIPTANS Almotriptan (Axert®) Eletriptan (Relpax®) Oral: 6.25–12.5 mg; may repeat in 2 Oral: 20–40 mg;may repeat in 2h h; max. 2 doses (25 mg)/24 h max. 40 mg/24 h Fewer S/E Contraindicated within 72 hours CYP3A4 inhibitors increase its of CYP3A4 inhibitors plasma concentration administration as they increase Good tolerability, lower SE than its plasma concentration Sumatriptan and zolmitriptan Frovatriptan (Frova®) Oral: 2.5 mg; may repeat in 4 h; max. 5 mg/24 h 1stlineagentinmigraineprophylaxis OCs and propranolol increase frovatriptan levels  TRIPTANS Rizatriptan (Maxalt®) Zolmitriptan (Zomig®) Oral: 5–10 mg; may repeat in 2 h; Oral/Oral disintegrating tablet : 2.5– max. 20 mg/24 h 5 mg; may repeat in 2 h; max. 10 mg/24 h Nasal Spray: 2.5 or 5 mg; may repeat in 2 h; max. 10 mg/24 h Faster relief compared to oral CYP1A2 inhibitors e.g. fluvoxamine triptans and cimetidine increase its plasma concentration. Its max dose should It is available as fast melt wafers be reduced into half Propranolol increases the Least tolerated? bioavailability of rizatriptan not sensitiveto fiians Better relief of nausea  EVIDENCE COMPARISON based on response w i 2hours thagine 0 Worthington, Irene, et al. "Canadian Headache Society Guideline: Acute drug therapy for migraine headache." The Canadian Journal of Neurological Sciences 40.S3 (2013): S1-S80.  CALCITONIN GENE-RELATED PEPTIDE RECEPTOR ANTAGONISTS (GEPANTS) CYP3A4substrate For the Acute Treatment of Migraine Ubrogepant (Ubrelvy®) chants alsousedfor Rimegepant (Nurtec ODT®) migraine prophylaxis Both effective within 2h in moderate to severe migraine (pain and associated symptoms) No direct comparison to other abortive agents. notgenerics new Iatns 11500 1. Lipton et al. Rimegepant, an oral calcitonin gene–related peptide receptor antagonist, for migraine. New England Journal of Medicine. 2019 Jul 11;381(2):142-9. 2. Dodick et al. Ubrogepant for the treatment of migraine. New England Journal of Medicine. 2019 Dec 5;381(23):2230-41. 3. Croop et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double- blind, placebo-controlled trial. The Lancet. 2019 Aug 31;394(10200):737-45. 4. Lipton et al. Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: the ACHIEVE II randomized clinical trial. Jama. 2019 Nov 19;322(19):1887-98.  DITANS For the Acute Treatment of Migraine – (Not yet in Canada) 5HT-1F receptor agonist NOvasoconstrictoreffect Neuron-specific; overcomes CV safety issues with triptans Lasmiditan (Reyvow®) Both effective within 2h in moderate to severe migraine ADR: temporary driving impairment (no driving for 8h post dose) dhow AE siness Ashina et al. Migraine: integrated approaches to clinical management and emerging treatments. The Lancet. 2021 Mar 25.  OTHER LINES OF THERAPY Ergot derivatives workswellbut triptans arebetter have lots of AE Non-selective 5-HT receptor agonists Also, they have effects on alpha, beta adrenergic and dopaminergic receptors The non-selectivity is responsible for their many side effect, limiting their use Adverse effects: Éramide Nausea and vomiting (very common; anti-emetics are given prior to iv dose) Chest discomfort Fatigue, dizziness, drowsiness Cramps Paresthesia Vasoconstriction  OTHER LINES OF THERAPY Ergot derivatives Contraindications: Ischemic heart disease Uncontrolled hypertension Pregnancy Renal or liver disease Co-administration with triptans Co-administration with CYP3A4 inhibitors Dihydroergotamine (DHE) available as paeal usedinhospital Nasal spray and parenteral The iv-route is reserved for severe resistant headache Metoclopramide 10 mg iv can be given as pre-dose  OTHER TREATMENT MODALITIES Antinauseants and prokinetics In headache disorders associated with nausea and vomiting May facilitate absorption of headache drugs Alternatives: Metoclopramide 10 mg po or iv (strongest evidence) Domperidone 10 mg po Dimenhydrinate 50 to 100 mg po gravol  so AVOID USE Opioids e.g. Codeine or Tramadol combination analgesics Butorphanol nasal spray Butalbital-containing combination analgesics risk for medoveruse headache risk for dependence  SCENARIO 6 Which agent would you choose for a female patient with migraine and: It is severe enough to limit daily activity nomedsbest Pregnant NSAIDs abs.CIin last trimester Peptic ulcer disease Previous stroke Gout it On citalopram 40 mg po daily for depression EEi aei iii ii  MIGRAINE PROPHYLAXIS When? The attacks are severe enough to limit the usual daily activity of the patient Headache is so frequent Four or more attacks per month Migraine medications are contraindicated or failed  MIGRAINE PROPHYLAXIS Beta blockers First-line agents Examples: Metoprolol, Propranolol and Timolol asinmsaii.ggept a Adverse effects: hypotension, bradycardia, bronchospasm, depression, insomnia Antiseizure Medications Topiramate Slow dose titration is recommended Valproic acid Gabapentin  MIGRAINE PROPHYLAXIS Tricyclic antidepressants 1st lineagent in tensiontypeheadache They act as analgesics in doses less than those used in depression Amitriptyline Nortriptyline take night Anticholinergic side effects, sedation Venlafaxine ACE inhibitors/ARBs Lisinopril Candesartan  MIGRAINE PROPHYLAXIS Calcium channel Blockers They act by modulating neurotransmitters function averyspecificformig prophylaxis Flunarizine: the most effective CCB but complicated depression and weight gain Verapamil: less effective than flunarizine but better tolerated. SE: Constipation, dizziness (limited evidence) very constipating Pizotifen Serotonin antagonist Low evidence  Prophylaxis oroxide iEn e.ie moemiiEiiittnin's Evidence for chronic migraine only Pringsheim, Tamara, et al. "Canadian Headache Society guideline for migraine prophylaxis." Can J Neurol. Sci 39.2 Suppl 2 (2012): S1-59.  CALCITONIN GENE-RELATED PEPTIDE (CGRP) ANTIBODY Erenumab (Aimovig®) Fremanezumab (Ajovy®) Galcanezumab (Emgality®) Eptinezumab (Vyepti®) Indication: Migraine prophylaxis (episodic and chronic) 1injection 700 CALCITONIN GENE-RELATED PEPTIDE RECEPTOR ANTAGONISTS (GEPANTS) T Atogepant (Qulipta®) - daily Rimegepant (Nurtec ODT®) – every other day Oral options Indication: Migraine Prophylaxis  MIGRAINE PROPHYLAXIS Initiate LOW and go SLOW Success defined by at least 50% reduction in headache frequency If headache occurs in a pattern e.g. menstrual cycle give NSAIDs at the time of the incident If the patient is healthy or with hypertension, IHD give beta blockers CCBs or ARBs/ACEIs if beta blockers are contraindicated If patient with depression or insomnia give TCAs  MIGRAINE PROPHYLAXIS If patient with seizure disorder or with bipolar disorder give an antiseizure medication If any of the recommended agents are CI or failed, with adequate trial period at target dose for 2 months, try the therapy in the next priority If 3 or more agents have failed, may consider CGRP antibodies or gepants zeromigrainesattack If headaches were controlled for 6-12 months, consider dose reduction or deprescribing Patient Factors Agent of Choice Rationale Comorbid mood disorder Tricyclic antidepressants Concurrent treatment of mood Venlafaxine disorder Comorbid insomnia Tricyclic antidepressants Improvement of sleep Gabapentin Melatonin Overweight/obese Topiramate Appetite suppression Candesartan (weight neutral) Comorbid hypertension Beta-blockers Concurrent treatment of Candesartan hypertension Comorbid epilepsy Valproic acid Concurrent treatment of Topiramate epilepsy Gabapentin Patients of childbearing age Propranolol Lower risk of teratogenicity who may become pregnant Medication averse Natural health products Better side effect profile Failed 2+ trials of prophylactic May consider calcitonin gene- Refractory patients may need therapy related peptide monoclonal more targeted treatment antibodies, atogepant, onabotulinumtoxinA Guay et al. Headache in Adults. eCPS (2023)  MIGRAINE IN EMERGENCY DEPARTMENT What agents? Sumatriptan SC Metoclopramide IV Prochlorperazine IV DHE Ketorolac 15 30mg Corticosteroids IV dexamethasone Associated with reduced headache recurrence for up to 3 days Opioids (avoid if possible)  mostseveretype of uni headache CLUSTER HEADACHE Source: http://www.natural-health-news.com/cluster-headache-causes-symptoms-diagnoses-treatment/ CLUSTER HEADACHE - MANAGEMENT Abortive Therapy Challenged by its short lived nature that makes oral therapy useless Prophylaxis Used to control a cluster period and produces remission Surgical intervention For refractory cluster headache Nerve radio frequency ablation Neurostimulation (e.g. deep brain stimulation, occipital nerve stimulation) CLUSTER HA- ABORTIVE THERAPY oxygen 100 givenallows80 ofpttorespond First-line: O2, sumatriptan S.C. Second-line: zolmitriptan and sumatriptan nasal spray Oxygen 7 L/min (6 -12 L/min) of 100% O 2 for 15 min via high flow mask 80% of patients respond in 30 min Mechanism of action is unknown No adverse effects Requires bulky equipment CLUSTER HA- ABORTIVE THERAPY overnasalspraybelfasterading Sumatriptan SC preferred The most effective abortive agent 75% of patients respond within 20 min 6 mg SC injection, higher doses are no more effective. Zolmitriptan nasal spray 5-10 mg Effective within 30 min Sumatriptan nasal spray 20 mg (1 spray) – less effective than the SC form Others: intranasal lidocaine, sc octreotide, DHE nasal spray  CLUSTER HEADACHE PROPHYLAXIS Verapamil First-line Well tolerated, safe and effective SE: constipation, bradycardia, hypotension at higher doses Lithium Target concentration 0.6-0.8 mEq/L Others: Galcanezumab (Emgality®) Transitional prophylaxis: short-term corticosteroids A week to 2 weeks Start with verapamil. Bridge until verapamil kicks in  MEDICATION-OVERUSE HEADACHE (MOH) Epidemiology Prevalence = 1-1.4% in the general population Highest rate is women in their 50’s; prevalence of 5% More commonly associated with barbiturate and opioid use Diagnostic Criteria A. B. treatment drugs triptans A. 10 days or more for ………………………… tylenol NSAIDs B. 15 days or more for ………………………… C. Headache has developed or markedly worsened during medication overuse  MEDICATION-OVERUSE HEADACHE theoretically 100 (MOH) preventable Treatment Patient education Stop/taper headache medications. Try prophylactic therapy If headache worsens may get IV DHE After control, limit the use of headache medications Role of the pharmacist?  SPECIAL POPULATIONS Pure menstrual migraine, or menstrually-associated migraine Use triptan BID starting 2 days prior to onset of menses, continuing for 5-6 days Frovatriptan 2.5 mg po BID seehr aising Naratriptan 1 mg po BID Zolmitriptan 2.5 mg BIT-TID Administer NSAID BID e.g. Naproxen on a standing basis 2 days prior to onset of menses, continuing for 5-6 days Other options: Supplementing estrogen around the menstrual period Risk of relapse after stopping the therapy Use of OCs without interruption riskfor vasoconstriction astroke Consider the risk of continued hormonal therapy and avoid in migraine with auras, smokers, focal neurologic symptoms, age > 35 (risk of stroke)  SPECIAL POPULATIONS Pregnancy Focus on nutrition, non-pharmacologic interventions TTH – approx. 30% report improvement Treat with analgesics, acetaminophen preferred Migraine – approx. 65% report improvement Acute: analgesics; possibly sumatriptan Prophylaxis: low-dose propranolol; Mg; possibly amitriptyline Cluster – few studies in pregnant women Acute: Treat with oxygen Alternatives: SC or intranasal sumatriptan for acute treatment Prophylaxis: Verapamil or prednisone; gabapentin as alternative  SPECIAL POPULATIONS Pregnancy - Summary Non-pharm Acetaminophen Ibuprofen, naproxen (avoid indomethacin; avoid NSAIDs in 3 rd trimester) If have to, codeine combinations at – avoid near term Avoid Ergots, barbiturates, valproic acid, topiramate ACEIs, ARBs, triptan (possible exception: sumatriptan) Refer if new onset headache to rule out serious causes e.g. eclampsia  SPECIAL POPULATIONS Lactation Non-pharm measures Acetaminophen, ibuprofen Avoid: ergots, barbiturates and opioids Sumatriptan could be used (more data than other agents) – but avoid in the immediate post partum period sina.is tas8atiTYnsitEsiiie Prophylaxis: propranolol, magnesium; VPA MONITORING HEADACHE DISORDERS Advise patient to keep a headache calendar Headache severity Associated symptoms Frequency of headache Adverse reactions Efficacy of certain agents Record use of headache medications  SUGGESTED READINGS Ashina et al. Migraine: integrated approaches to clinical management and emerging treatments. The Lancet. 2021 Mar 25. Becker, Werner J., et al. "Guideline for primary care management of headache in adults." Canadian Family Physician 61.8 (2015): 670-679. Worthington, Irene, et al. "Canadian Headache Society Guideline: Acute drug therapy for migraine headache." The Canadian Journal of Neurological Sciences 40.S3 (2013): S1-S80. Pringsheim, Tamara, et al. "Canadian Headache Society guideline for migraine prophylaxis." Can J Neurol. Sci 39.2 Suppl 2 (2012): S1-59. DiPiro, J. Pharmacotherapy: a pathophysiologic approach. New York: McGraw-Hill Medical. Headache Chapter.