PHAR 5717 Headache and Migraine Lecture 2024 PDF

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COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been copied and communicated to you by or on behalf of the University of Sydney pursuant to Part VB of the Copyright Act 1968. (The Act). The material in this communication may be subject to copyright under the Act. Any further copying or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. The University of Sydney Page 1 PHAR 5717 Headaches and Migraines Presented by: Dr Maya Saba [email protected] The University of Sydney Page 2  Acknowledgement of Country We would like to acknowledge the Traditional Owners of the land on which we meet. We would also like to pay our respects to Elders past, present and emerging. The University of Sydney Page 3  Learning Objectives – Recognise possible underlying conditions associated with headaches – Become familiar with the International Headache Society classification: The International Classification of Headache Disorders-3rd edition (ICDH-3) – Understand the pathophysiology of tension-type headaches and migraines – Identify common symptoms of tension-type headaches and migraines – Recognise alarm symptoms and referral triggers for tension-type headaches and migraines – Recommend non-pharmacological, pharmacological and prophylactic interventions for tension-type headaches and migraines – Explain the underlying cause of medication over-use headaches The University of Sydney Page 4  Headache – Universal human experience – Most common pain experienced by humans – Most common complaint in medicine and neurology – Evaluation ranging from straightforward to challenging More than 200 different types of headaches https://www.health.harvard.edu/diseases-and-conditions/top-7-reasons-you-have-a-headache The University of Sydney Page 5  Headache Classification – International Headache Society Classification universally accepted The International Classification of Headache Disorders-3rd edition The University of Sydney Page 6  International Classification of Headache Disorders Referral The University of Sydney Page 7 Rutter, 2021  Secondary Headache – Symptom of an underlying medical condition/disease or drug/medication- induced Brain tumour Concussion Cervical spine disorders Cerebrospinal fluid disorders Stroke Blood clots Hypertension Glaucoma Meningitis Referral Encephalitis Infections Metabolic disorders Dehydration Drugs (alcohol, cocaine, marijuana, CO...) Medications (CCB, nitrates, sildenafil, hormones…) The University of Sydney Page 8  Primary Headaches – Most common presentation within community pharmacy settings – 80-90% of community pharmacy presentations of headache are tension- type headaches – 10% are migraines – Very few with other primary headaches or secondary headaches – Location as a key indicator of type https://www.medicalnewstoday.com/articles/headache-chart#overview The University of Sydney Page 9  Primary Headaches Severe pain Red eye on affected side Eye tearing Nasal stuffiness Agitation Unable to lie down Onset at 20-40 years of age Rare The University of Sydney Page 10  Primary Headaches Sensation of tightness or band-like pressure across forehead Tenderness in scalp, neck and shoulder No nausea or vomiting The University of Sydney Page 11  Primary Headaches Throbbing or pulsating pain Nausea Vomiting Sensitivity to light and sound The University of Sydney Page 12  Differential Diagnosis Questions – Age – Onset of headache – Frequency, timing and duration – Location of pain – Severity of pain – Triggers – Associated symptoms https://www.coliquio.de/wissen/onkologie-kompakt-100/fallserie-diagnoseraetsel – Recent injury – History of medication use (Medication Overuse Headache?) The University of Sydney Page 13  Red Flags for Referral – Sudden and/or severe onset – First ever headache with focal neurological signs, confusion or drowsiness – Patient older than 50 years – Onset after head trauma or injury – Frequency/severity increases over weeks to months – New onset in patient with HIV, cancer or is immunosuppressed – Signs of systemic illness (e.g. fever, rash, neck flexion stiffness) – Papilloedema (swelling of the optic disc due to elevated intracranial pressure) – Positional headache (e.g. worse when lying down) and cough headache (especially if prolonged) – Headache unresponsive to analgesics The University of Sydney Page 14  Differential Diagnosis Rutter, 2021 The University of Sydney Page 15  Tension-Type Headache The University of Sydney Page 16  International Classification of Headache Disorders https://ichd-3.org/2-tension-type-headache The University of Sydney Page 17  Tension-Type Headache (TTH) – Most common type of primary headache – Lasts 30 mins - 7 days – Bilateral dull pain that feels like pressure or tightness – Mild to moderate intensity – Not associated with nausea and vomiting – May be associated with photophobia or phonophobia (rarely) Tension Headache Episodic Chronic Frequent Infrequent ≥ 15 days/month 1-14 days/month 3 months for > 3 months The University of Sydney Page 18  Pathophysiology of TTH – Not fully understood – Increased sensitivity to pain – Peripheral pathway Altered nociception (detection of painful stimuli) of pericranial myofascial tissue Lower tolerance to mechanical, thermal and electrical stimuli i.e. altered pain perception More tender pericranial myofascial tissue – Central pathway Increased excitability of CNS Decreased descending inhibition in supraspinal structures in the CNS Increased pain sensitivity – Epigenetic - family history, environmental factors Onan et al., 2023 The University of Sydney Page 19  Non-Pharmacological Treatment – Regular sleep schedules – Adequate hydration – Stress management – Relaxation techniques (meditation, mindfulness) – Cognitive behavioural therapy (CBT) – for psychological distress – Physical relaxation – Physiotherapy – neck muscle stretching and endurance program – Acupuncture (≥ 6 sessions) – Aerobic exercise – Trigger avoidance https://www.healthshots.com/mind/mental-health/10-stress-management-techniques-to-ease-your-life The University of Sydney Page 20  Pharmacological Treatment – Simple nonopioid analgesics as mainstay of therapy – Wait 4-6 hours before repeating dose if needed Paracetamol Aspirin NSAIDs 1g orally; Max 4g 600 to 900 mg; Ibuprofen 400 mg; in 24 hours Max 2g in 24 max 2.4 g in 24 hours hours Diclofenac 50mg; Max 150mg in 24 hours Naproxen 500 to 750mg; Max 1250mg in 24 hours eTG, 2023 The University of Sydney Page 21  Prophylaxis Therapy – Simple analgesics lose efficacy with time and with increasing headache frequency – Consider prophylaxis therapy to reduce analgesic use Amitriptyline Mirtazapine 15-30 10mg night mg night for 8-12 weeks OR If effective, continue OR Nortriptyline 10mg for 6 months then Venlafaxine 75mg, night withdraw morning after food Increase dose by If ineffective after up to 150 mg daily for 8- 10mg every 7 8-12 weeks 12 weeks days, max 75mg Refer to night, for 8 weeks specialist eTG, 2023 The University of Sydney Page 22  Migraines The University of Sydney Page 23  International Classification of Headache Disorders https://ichd-3.org/1-migraine The University of Sydney Page 24  Migraine – Recurrent attacks lasting 4-72 hours – Typically one-sided – Pulsating pain – Moderate to severe intensity – Pain aggravated by routine physical activity – Nausea and/or vomiting – Photophobia, phonophobia and osmophobia With Aura Without Aura (Classic Migraine) (Common Migraine) Reversible focal Aura symptoms affect neurological symptoms vision, senses, speech 75% of migraine that usually develop over and/or language, motor cases 5 to 20 minutes and last function, brainstem and for less than 60 minutes retina The University of Sydney Page 25  Migraine with Aura https://www.allaboutvision.com/conditions/ocular-migraine.htm The University of Sydney Page 26  Migraine Triggers – Environmental factors: hot wind, changes in barometric pressure – Stress: emotions, loud noise, flashing light – Hormonal changes: puberty, menstruation – Food: chocolate, cheese, citrus, preservatives, alcohol – Drugs: Oestrogens, caffeine – Inadequate sleep: changes in sleep patterns – Dehydration The University of Sydney Page 27  Migraine Phases The University of Sydney Page 28 American Migraine Foundation, 2023  Pathophysiology of Migraines – Unknown exact pathophysiology – Vascular theory - initial intracerebral vasoconstriction as the cause of the aura, followed by an extracerebral vasodilatation causing the headache – Inflammation hypothesis - activation of trigeminal nerve terminals in the meninges and extracranial vessels as the primary event in a migraine attack, inducing release of inflammatory mediators and neuropeptides e.g. calcitonin gene-related peptide (CGRP) – Genetic factors and environmental triggers BMJ, 2011 The University of Sydney Page 29  Pathophysiology of Migraines Prodrome Aura Headache Postdrome High 5-HT i.e. Abnormal cortical Low 5-HT i.e. Activation of vasoconstriction of and brain stem protective brainstem nucleus intracranial activity intracranial Widespread vessels vasodilation vasoconstriction Impaired blood Increased mediated by an flow, starting at cerebral blood α2-adrenoceptors visual cortex flow Symptom such as Activation of flashing lights, trigeminal nerves sensitivity to light, Unilateral smell and noise pulsating pain The University of Sydney Page 30  Non-Pharmacological Treatment – Cold packs over the forehead or back of skull (supraorbital and greater occipital nerves) – Hot packs over the neck and shoulders (innervation of scalp) – Rest in a quiet dark room – Avoid movement or activity (including reading or watching television) – Maintain fluid intake – Physical therapies (e.g. massage, stretching, acupuncture, heat, postural correction) – Neck stretches and self-mobilisation https://homebuddy.store The University of Sydney Page 31  Pharmacological Treatment – Simple nonopioid analgesics as mainstay of therapy – Higher dose ranges as compared to TTH – Wait 4-6 hours before repeating the dose if needed – Use < 15 days/month Paracetamol Aspirin NSAIDs 1g orally; Max 4g in 900-1000 mg; Max Ibuprofen 400 mg- 24 hours 4g in 24 hours 600; max 2.4g in 24 hours Diclofenac 50mg; Max 200mg in 24 hours Naproxen 500- 750mg; Max 1250mg in 24 hours eTG, 2023 The University of Sydney Page 32  Pharmacological Treatment – If response to nonopioid analgesic suboptimal add antiemetics (esp. metoclopramide)--improve treatment response by increasing drug absorption Metoclopramide Domperidone Ondansetron Prochlorperazine 10mg orally; 10-20 mg; Max 4-8 mg orally; 5-10 mg orally; Max 30 mg 30 mg Max 16 mg Max 30 mg eTG, 2023 The University of Sydney Page 33  Pharmacological Treatment – If no response to nonopioid analgesics (±antiemetic) triptans – Selective 5-hydroxytryptamine (5-HT) receptor agonists with high affinity for 5-HT1B and 5-HT1D receptors – Inhibit abnormal activation of trigeminal nociceptors Constriction of cranial vessels Reduction in cerebral blood flow Inhibition of peripheral nociceptors Reduction in CGRP Inhibit pain transmission in CNS The University of Sydney Dominguez 2016 Page 34  Triptans – To be taken when headache is beginning to develop (not during aura or severe attacks) – Trial and error to find the right triptan – Could combine with nonopioid analgesic – Flexibility of dosage forms (sublingual tablet, nasal spray) – If response to first dose of triptan, wait 1-4 hours before repeating dose (to avoid additive vasoconstriction) – If no response to first dose of triptan, do not take second dose for the same migraine episode (could be trialled in future migraines) – Limit triptan use to < 10 days/month – Comparable safety profile across different triptans – Response varies between patients – Same individual could respond differently to different triptans – Do not give triptan within 24 hours of ergometrine or ergometrine within 6 hours of a triptan (risk of vasospasm such as coronary vasoconstriction) – SNRI and SSRI users can take triptans (monitor for serotonin toxicity due to 5HT activity) The University of Sydney Page 35  Triptans – Common adverse effects Tingling Heat pain Heaviness/tightness in the body Drowsiness--do not operate machinery Weakness Fatigue – Precautions Cerebrovascular/Cardiovascular disease: CI in uncontrolled hypertension and peripheral vascular disease, coronary vascular disease, transient ischaemic attack Elderly: potential increased risk of cardiovascular effects Pregnancy/Breastfeeding: avoid if possible but sumatriptan is agent of choice if needed The University of Sydney Page 36  Triptans Triptan Efficacy Onset of Route of MAO-A Action Administration Substrate Sumatriptan Reference triptan 30-60 mins Oral dose, Yes, i.e. CI in injection, MOAI users nasal Spray Zolmitriptan Similar efficacy and 30-60 mins Oral dose Yes, i.e. CI in adverse MOAI users effects Eletriptan Similar efficacy and 30-60 mins Oral dose No, i.e. can be adverse used with MAOI effects Rizatriptan Similar efficacy 30-60 mins Oral dose and Yes, i.e. CI in wafers, taken MOAI users without water Naratriptan Slower onset of action 2 hours Oral dose No, i.e. can be and less used with MAOI effective than sumatriptan but fewer adverse effects The University of Sydney Page 37  Triptans Triptan Dosage Wait Time Before Max Daily Dose Repeating Sumatriptan 50-100 mg orally 2 hours 300 mg 6 mg SC 1 hour 12 mg 20 mg intranasally 2 hours 40 mg Zolmitriptan 2.5-5 mg orally 2 hours 10 mg Eletriptan 40-80 mg orally 2 hours 160 mg Rizatriptan 10 mg orally 2 hours 30 mg Naratriptan 2.5 mg orally 4 hours 5 mg The University of Sydney Page 38  Migraine Prophylaxis – For patients Requiring treatment for acute migraine > 2-4 days/month Poor response to treatment taken at start of attack Severe monthly migraine attacks with impaired QOL – Only reduces frequency and severity of attacks, treatment still required – One prophylactic treatment at a time – Use lowest effective dose for 8-12 weeks, then assess efficacy – 3-6 months and review – Caution any adverse effects – Caution patient’s underlying medical conditions and medications – CGRP antagonists (monoclonal antibodies) trialled for prevention after failure of first line therapies The University of Sydney Page 39  Migraine Prophylaxis eTG,2023 The University of Sydney Page 40  Other Migraine Supplements – 3 months trial – Low risk – Can be used in combination Riboflavin Magnesium Co-Enzyme Q10 (Vitamin B2) 400-650 mg daily 150-300 mg daily 200 mg twice daily Used for aura in Prevents migraine Prevents migraine migraines (cortical Reduces brain Improves brain spreading mitochondrial mitochondrial function depression) dysfunction Prevents narrowing of blood vessels The University of Sydney Page 41  Lifestyle Modifications – Regular sleep schedules – Minimal variation in blood glucose concentrations (e.g. eating regular meals, avoiding excess simple carbohydrates) – Adequate hydration (e.g. drinking 1.5 to 2 litres water daily) – Limited caffeinated beverages (1 to 2 cups daily) – Regular exercise (aiming for 30 to 40 minutes, 3 to 4 times a week; walking is a good option, as exercise that involves jumping or running often provokes migraine in people who have them regularly) – Regular physiotherapy – Good workplace ergonomics (especially when using a computer) and regular short breaks (to stretch and rest eyes) – Regular use of a relaxation technique (e.g. meditation, mindfulness, yoga, breathing techniques, progressive muscular relaxation), especially if stress is a trigger (biofeedback and cognitive behavioural therapy may help) – Avoidance of patient's known triggers (e.g. alcohol, monosodium glutamate, citrus fruit, chocolate, preserved meats, perfume) – Use of a headache diary to record days with and without headache, severity, duration, suspected triggers and use of and response to medicines https://activities.nps.org.au/nps-orderform/Resources/NPS_Headache_Diary_0612.pdf The University of Sydney Page 42  Medication Overuse Headache (MOH) – Rebound headache as the dose wears off – Could result in a secondary headache disorder – Exact pathophysiology is unknown – More common in patients with TTH and migraines – Patients at risk have headaches > 15 days/month for > 3 months AND Taking triptans, opioid analgesics, ergotamines > 10 days/month Taking nonopioid analgesics > 15 days/month – Typically resolves over a few weeks after overuse is stopped https://www.everydayhealth.com/migraine The University of Sydney Page 43  Medication Overuse Headache (MOH) Withdrawal of Bridging Therapy for Restarting Acute Causative Medication Opioid and Triptans Medications Withdrawal Consider prophylaxis Naproxen modified- Restrictions on usage before withdrawing release 750 mg orally, (< 10 days/month for analgesic once daily for 5 days opioids and triptans in the first week, then and < 15 days/month Tapering down vs 3 to 4 days per week for simple analgesics) abrupt discontinuation for 2 weeks, then stop Prednis(ol)one 50 mg orally, once daily for 3 days, then decrease dose gradually over 7 to 10 days, then stop The University of Sydney Page 44  Summary – Headache most commonly presented symptom in community pharmacy – TTH and migraine most common types of headaches – Differential diagnosis based on location, duration, frequency, severity and associated symptoms – Management Non-pharmacological/lifestyle modifications Pharmacological Prophylaxis – Role of pharmacist to ensure proper management of pain while minimising risk of MOH The University of Sydney Page 45  Further Resources – Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders. 3rd edition. Available from: www.ichd-3.org – Migraine & Headache Australia. Available from: http://headacheaustralia.org.au/types-of-headaches – Migraine Australia. Available from: https://www.migraine.org.au – Rutter P. Community Pharmacy: Symptoms, Diagnosis and Treatment. 5th edition. – Therapeutic Guidelines: Neurology – Australian Medicines Handbook – APF26 Australian Pharmaceutical Formulary and Handbook The University of Sydney Page 46  Any Questions? The University of Sydney Page 47