Migrainous headache, the menstrual cycle and pregnancy Dr Manuela Fontebasso Headache Specialist, Author and Headache Education Facilitator
What sort of headaches? Migraine with and without aura Tension Type Headache Cluster Headache Episodic or Chronic Daily headaches Chronic migraine Medication overuse Headache 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
Migraine Lasts from 4 hours to 3 days May, or may not be associated with aura Usually a moderate to severe pain Is associated with symptoms and features nausea, vomiting, diarrhoea light, sound smell sensitivity feel clumsy, dizzy speech affected Tends to prevent day-to-day activities Acute treatment may not always be effective Increasingly frequent headache days increases the possibility of medication overuse headache developing with time Consider preventative medication if the number of headache days edges towards 6 to 8 days each month 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
Tension Type Headache Usually short lived Usually a mild to moderate pain Is NOT associated with symptoms or features Tends NOT to prevent day-to-day activities Increasingly frequent headache days increases the possibility of medication overuse headache developing with time Consider preventative medication if the number of headache days edges towards 6 to 8 days each month 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
Cluster Headache Lasts from 15 minutes to 3 hours Usually a severe to very severe pain Is associated with symptoms and on the same side of the headache e.g. red eye, watery eye, runny or blocked nose Tends to cause restlessness, agitation and sleep disturbance Acute treatment may not always be effective, especially if the attacks are short lived Preventative medication may be successful in shortening an episode of cluster, and can prevent a flare of symptoms of chronic cluster headache 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
Medication Overuse Headache A chronic headache tending to occur on a daily or near daily basis Varies from a mild to a severe headache, through the day and from day-to-day Can, on occasion, prevent day-to-day activities When acute medication is stopped, the headache will get worse before it gets better but the only way to break the cycle Use preventative medication to manage the headache pain whilst stopping acute medication 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
Optimising treatment Treat the right headache with the right treatment Tailor the treatment to best meet the need of the patient involve the patient in the decision making Agree a clear plan optimise acute treatment minimise headache days agree a review session Engage the GP or Practice Nurse in the support process Review the patient until they feel in control of their headache 1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed January 2017 2. Headache Classification Committee of the International Headache Society. ICHD-3 beta. Cephalalgia 2013; 33 (9) 627 808
The Acute treatment of Migraine
Goals of Acute Migraine Treatment Treat high impact headache only minimises risk of medication overuse headache developing Treat the aura or premonitory symptoms early may maximise the effect of the headache treatment may prevent the onset of the headache or reduce its severity Treat the headache early To make the treatment more effective Increase the chance of being headache free at 2 hours To minimise the chance of headache recurrence reduce the total number of headache days minimise the risk of medication overuse headache developing
CLINICAL PATTERNS - MIGRAINE - Signs & Symptoms Headache Normal Appetite Awake/Sleep Tired yawning Light tolerance Noise Smell Fluid balance Craving Heightened perception Fluid retention Anorexia Nausea Vomiting Vomiting Sleepy yawning Deep sleep Photophobia Photophobia Phonophobia Phonophobia Osmophobia Osmophobia Limited food tolerance Tired Feeling High Low Diuresis Normal Normal I Premonitory II Aura III Headache IV V Resolution Recovery Normal
Diet and Lifestyle Advice Diet regular meals adequate fluids combination triggers Stress Counselling, relaxation, yoga Sleep patterns shifts, travel, social functions The higher the threshold the less likely you are to get a headache The lower the threshold the more likely you are to get a headache Encourage you to put yourself top of the heap some of the time Ideally EVERY day
Goal setting Acute treatment Complete resolution of symptoms within 2 to 4 hours with no recurrence of symptoms during that attack treat early, ideally within one hour of the start of the headache use a combination to maximise the benefit NSAID, anti-emetic and/or triptan If the first combination does not work try another AT REVIEW Check the dose or delivery system of the medication the patient is taking Check timing premonitory, aura or headache How long before the patient is headache free? Does the headache return that day or the next day? What does the patient do if the headache returns during this attack?
1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed Sept2017 2. BASH Guidelines, available at: http://www.bash.org.uk/wp-content/uploads/2012/07/10102-bash-guidelines-update-2_v5-1-indd.pdf accessed Sept 2017 Acute treatment simple painkillers Soluble aspirin 900mg, domperidone 10 to 30mg or metoclopramide 10mg might have tried this but at a lower dose Naproxen 500mg to 1g, no more than once a day often of benefit for those who have menstrual migraine Ibuprofen 400mg to 600mg up to three times a day useful as dose can be repeated in the day Diclofenac 100mg, as a suppository if early nausea and vomiting Migramax, 1 sachet in water and repeat in 2 hours if needed for those patients who can t take or tolerate triptans Paracetamol, in a soluble format, 1500mg as a single dose if unable to take NSAID
Acute treatment -Triptans Migraine specific Only to be taken as the headache starts May cause side effects which include tingling, chest tightness, throat tightness Should stop all the symptoms of the attack Don t work for everybody 50 to 80% of people get a reduction in headache 20 to 50% become headache free 25 to 50% of people find the headache can return There are 7 different triptans available as a tablet, a wafer, a nasal spray, an injection Minimise perceived cost by optimising acute treatment and minimising headache days
1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed Sept2017 2. BASH Guidelines, available at: http://www.bash.org.uk/wp-content/uploads/2012/07/10102-bash-guidelines-update-2_v5-1-indd.pdf accessed Sept 2017 Triptans available in the UK Sumatriptan 50 & 100mg tablet 20mg nasal spray 6mg injection 10mg Adolescent nasal spray for 12 to 18 year olds RADIS 50 &100mg Zolmitriptan 2.5 mg tablet 2.5 & 5mg rapimelt 5mg nasal spray Naratriptan 2.5mg tablet Rizatriptan 5 & 10mg tablet 10mg wafer Almotriptan 12.5mg tablet Eletriptan 20 & 40mg tablet best taken as 80mg dose Frovatriptan 2.5mg tablet
Triptans Contraindications Not licensed under 18 or over 60 sumatriptan adolescent nasal spray is licensed for 12 to 18 year olds Significant liver disease History of cardiovascular disease angina, previous heart attack TIA or previous stroke Badly controlled blood pressure if well controlled then can be taken Using St John s Wort Using ergotamine At the same time as taking another triptan
Acute treatment top tips Only take the triptan at the start of the headache Raise awareness of the headache threshold Think about diet and lifestyle factors to raise the headache threshold Optimise the acute treatment to prevent headache recurrence offer flexibility in dose and delivery system Raise awareness that if the treatment becomes less effective there is a probability that medication overuse headache is developing If there are more than 6 to 8 treatment days a month there is a probability that medication overuse headache is developing
Medication overuse Headache
Medication overuse Headache Associated with the uncritical use of painkillers Use them more often Increase the strength of the tablets taken Take them just in case Can occur when taking Simple painkillers more often than four days in the week Combination painkillers more often than three days in the week Triptans, opiates or ergotamine more often than two days in the week Only when treating headache not other causes of pain Unless you have a history of migraine
Headache intensity Medication Overuse Headache* Increased frequency of headache, associated with increased frequency of the use of painkillers. Withdrawal of all painkillers Daily headache with spikes of more severe pain Stop all acute analgesic medication Return of episodic headache Migraine attacks * Adapted from MIPCA guidelines, 1997 Frequent daily headaches
Codeine the hidden extra Boots Tension Headache relief - 10mg Codis 500-8mg Nurofen Plus - 12.8mg Panadol Ultra - 12.8mg Paracodol - 8mg Propain - 10mg Solpadeine Max - 12.8mg Solpadeine Migraine 12.8mg Syndol - 10mg Veganin - 8mg
Caffeine friend or foe? Coffee, 150ml, 60 to 150mg Coffee, decaff, 150ml, 2 to 5mg Tea, 150ml, 40 to 80mg Hot cocoa, 150ml, 1 to 8mg Diet coca cola, 12oz, 45mg Coca cola, 12oz, 64mg Dr Pepper, 12oz, 61mg Pepsi Cola, 12oz, 43mg WHY? Because 200mg of caffeine taken on a daily basis for 2 weeks can cause a headache when the caffeine is stopped or the level drops
Hidden caffeine Anadin extra 45mg 5 tablets is 220mg Anadin maximum strength 32mg 6 tablets is 192mg Boots Tension Headache Relief 30mg 6 tablets is 180mg Hedex Extra 65mg Panadol Extra 65mg Propain 50mg 4 tablets is 260mg 4 tablets is 260mg 4 tablets is 200mg Solpadeine Headache 65mg 4 tablets is 260mg Syndol 30mg 6 tablets is 180mg
Medication overuse Headache Treat migraine aggressively and effectively BUT not too often Keep treatment days to 6 or less each month Ten triptan days per month over a 3 month period means there is a probability that triptan rebound headache is developing
Get back to episodic migraine Optimise diet and lifestyle Plan a stop date THEN STOP ALL your painkillers but tell the patient to continue to take all their medication for other health problems Start the preventative medication on the same day The patient MUST NOT take any acute treatment for at least 6 to 8 weeks Headaches will get worse before they get better Review the number of headache days every month Plan how to treat the migraine
Preventative headache treatment
1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed Sept2017 2. BASH Guidelines, available at: http://www.bash.org.uk/wp-content/uploads/2012/07/10102-bash-guidelines-update-2_v5-1-indd.pdf accessed Sept 2017 Preventative treatment the challenge There are no ideal drugs They can reduce the number of headache days BUT will not stop all the headaches Any drug has the potential to cause side effects BUT only in some of the people some of the time Drug choice may be guided by other health problems Sometimes the side effects form part of the plan The drug chosen must be taken long enough to work The drug chosen must be taken at a high enough dose to work Start low and build slow To minimise side effects and find the lowest effective dose
1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed Sept2017 2. BASH Guidelines, available at: http://www.bash.org.uk/wp-content/uploads/2012/07/10102-bash-guidelines-update-2_v5-1-indd.pdf accessed Sept 2017 Drugs used in headache reduction Beta-blockers Propranolol Atenolol Metoprolol Tricyclic antidepressants Amitriptyline Imipramine Nortriptyline Dosulepin ARB Candesartan ACE Lisinopril Anti-epilepsy drugs Topiramate Sodium valproate Gabapentin If also have chronic pain Calcium Channel Blockers Verapamil Cluster headache only Pizotifen Methysergide Tertiary centre only
Preventative medication goal setting Aim to reduce the total number of headache days Increase the effectiveness of any acute treatment Agree an initial target dose Agree a dose titration schedule Agree a review date Use a diary card to review the response to acute medication and the change in headache days
1. Clinical Guidance 150, available at: http://guidance.nice.org.uk/cg150/niceguidance/pdf/english Accessed Sept2017 2. BASH Guidelines, available at: http://www.bash.org.uk/wp-content/uploads/2012/07/10102-bash-guidelines-update-2_v5-1-indd.pdf accessed Sept 2017 Most common preventatives used Propranolol Slow release, single daily dose Up to maximum 240mg Amitriptyline 10 to 100mg At night or in split doses 2 hours before bedtime Or 12 hours before you want to get up Candesartan 4mg to 16mg Lisinopril Start at 2.5mg Increase by 2.5mg increments every 2 weeks Max dose of 20mg Topiramate 50mg twice a day Start at 15mg or 25mg If side effects develop step back to last best tolerated dose
Preventative medication at review How good is the acute treatment response? How quickly does the pain become more manageable? How soon do you get back to normal? How soon does the headache go completely? Does the headache go away and stay away? How effective is the preventative medication? Is there a reduction in the number headache days? Are there any side effects from the medication?
Preventative medication changes to consider Optimise the acute treatment response Try each treatment or treatment combination Evaluate the response in three consecutive attacks Optimise the preventative treatment response Review side effects Consider a dose change if few or no side effects Consider a drug change If side effects are a problem If the maximum dose is reached Agree a review appointment
Preventative medication - conclusion Preventative medication can help some of the people some of the time The goal is to reduce the number of headache days with the fewest side effects at the lowest dose Different headaches need different preventative drugs Different patients respond to different drugs and dosages Finding the right drug and the right drug dose takes time and persistence
Contraception, Menstrual migraine, Migraine in pregnancy and breast feeding I am not going to talk about the peri and post menopause and HRT
Oestrogen Fact or myth In adults migraine is 3 times more common in women than men Studies show that the size and speed of the fall in oestrogen levels prior to the start of the period is associated with the onset of migraine Prostaglandins have been shown to be able to trigger a migraine like headache Prostaglandins levels in the blood rise during a migraine attack released by the lining of the womb during a period Bille B Migraine in school children Acta Paediatr Scand 1962; 51 suppl 136: 1-151 Somerville BW, Neurology 1972; 22:355-365 and 1972; 22: 824-828 Fettes I. PostGrad Med 1997; 101: 67-77
Migraine and the Menstrual Cycle Menstrual Migraine without aura day 1 +/ - 2 days of each cycle At no other times in the cycle Affects 10% of women Menstrually Related Migraine without aura day 1 +/ - 2 days of each cycle AND at other times in the cycle Need diary cards to make the diagnosis Headache classification Subcommittee of the International Headache Society The International Classification of Headache Disorders 2 nd edition Cephalalgia 2004 24 Suppl 1 1-60
Migraine and Premenstrual Syndrome Attacks occur in second half of cycle after ovulation Associated with other PMS symptoms Need diary cards to make diagnosis PMS symptoms must clear on Day 1 of period Women with PMS may experience severe headache symptoms but not actually fulfil IHS criteria for migraine. Headache classification Subcommittee of the International Headache Society The International Classification of Headache Disorders 2 nd edition Cephalalgia 2004 24 Suppl 1 1-60
Migraine and Stroke Risk Migraine with aura is associated with an increased risk of ischaemic stroke There is NO evidence to show that there is an increased risk of stroke in migraine sufferers over the age of 45 years The annual incidence of stroke in Europe is 1 to 3 per 100,000 women under the age of 35 years 10 per 100,000 women over the age of 35 years The risk is VERY SMALL but important to consider other risk factors 1.Gudmundsson LA, Scher AI, Aspelund T et al Migraine with aura and risk of cardiovsacular and all cause mortality in men and women/bmj 2010 341 c 3966 2. The IHS Task Force. Cephalalgia, 2000; 20: 155 6 3. MacGregor EA. Hormonal Contraception and migraine. Faculty of Family Planning Fact Sheet. Review no. 2001/01
Combined hormonal Contraceptives (CHC), migraine and stroke risk CHC s are a risk factor for ischaemic stroke Relative risk (RR) is 16 if you have migraine Smoking increases the risk of ischaemic stroke RR is 10 if you have migraine Risks are additive RR is 34.4 if you take CHC s and smoke and have migraine Vital to minimise all vascular risk factors if you have migraine with aura (Tzourio et al BMJ 310: 830-833 and Chang et al BMJ 318: 13-18)
CHC s and current UK advice CHC s can be used if NO aura and NO additional risk factors CHC s can be used with caution if NO aura and one additional risk factor CHC s CANNOT be used if there is aura NO aura BUT more than one additional risk factor There are severe and prolonged attacks Ergotamine is being used (which it should not be) (WHO Improving Access to Quality Care in Family Planning. Medical Eligibility Criteria for Use. Second edition. WHO/RHR/00.02.) (MacGregor EA, Guillebaud J. Recommendations for clinical practice. Br J Fam Planning 1998; 24: 53-60) (Bousser M-G, Kittner SJ. Oral contraceptives and stroke. Cephalalgia 2000; 20: 183-189) (EA MacGregor Migraine and use of combined hormonal contraceptives: a clinical review J Fam Plann Reprod Health Care 2007; 33 (3): 159 169 )
Menstrual migraine acute treatment Attacks often harder to treat Attacks associated with a greater degree of disability Attacks associated with more aggressive symptoms and features Have to find most effective acute treatment means maximum dose of any acute drug means use drugs in combination Triptan, NSAID and anti-emetic EA MacGregor Managing Menstrual migraine: A clinical review J Fam Plann Reprod Health Care 2007; 33 (1): 36-47
Menstrual migraine diary Days of the month At least three consecutive months M M M M M H M M M M M H H H M M M M M M M M M M H H M M M M H H H H M = Menstruation H = Headache
Menstrual migraine using NSAID or triptan Using a non-steroidal anti-inflammatory drug (NSAID) Naproxen 500mg up to twice daily (bd) or mefenamic acid 500mg up to three times daily (tds) Using a triptan Frovatriptan 2.5mg bd, Zolmitriptan 2.5mg tds or Naratriptan 1mg bd Use an NSAID (naproxen) and Frovatriptan Start 2 to 3 days before the expected onset of the attack and use for 7 days Can extend NSAID into period if needed EA MacGregor Managing Menstrual migraine: A clinical review J Fam Plann Reprod Health Care 2007; 33 (1): 36-47
Menstrual migraine without aura Migraine in the pill free week Use an oestrogen dominant pill Marvelon or Dianette Tricycle the COCP take three packets consecutively BUT if get break through bleeding or not tolerated Revert to monthly cycle Use NSAID daily in pill free week Seasonale is a CHC available in the USA designed to give women one period in the spring, summer, autumn and winter. It contains 30mcg ethinyloestradiol and 150mcg levonorgestrel in each pill Lybrel is a CHC (now only available as a generic called Amethyst) in the USA which is taken continuously. It contains 20mcg ethinyloestradiol and 90mcg levonorgestrel in each pill Use top up topical oestrogen (as patch or gel) in pill free week Current evidence suggests you can take the COCP continuously and come to no harm EA MacGregor Managing Menstrual migraine: A clinical review J Fam Plann Reprod Health Care 2007; 33 (1): 36-47
Acute treatment safety profiles in pregnancy Amundsen, S. et. al. Nat. Reviews Neurol.11, 209 219 (2015) Thanks to Dr Shazia Afridi for this slide
Triptan meta-analysis 2015 The challenges No randomised controlled trials Study identified publications that looked at pregnancy outcomes following pre natal exposure to triptans from 1991 to 2013 Identified six studies, 4,208 infants of women who had used sumatriptan or any other triptan Found NO increased rate of major congenital malformations prematurity BUT there was an increased risk of spontaneous abortion Marchencko A et al Headache; 55: 490-501
Triptan use in pregnancy Women who have used triptans in early pregnancy can be reassured that exposure has not been associated with adverse outcomes Triptan use during pregnancy is only recommended if no other treatment is effective it is always a balance of risk versus benefit informed decision making Sumatriptan safety data base shows 4.3% risk of first trimester birth defects 3 to 5% have been shown in the general population Rizatriptan safety data base similar results but fewer numbers MacGregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007:33 (2) 83 to 93
Decision making while breastfeeding Need to consider bioavailability amount found in breast milk limited data available summary of product characteristics recommend caution avoid breast feeding for 12 to 24 hours after dose Sumatriptan has the most extensive data base low level of excretion in breast milk 0.5% of oral dose Eletriptan one study, 80mg dose 0.02% of dose in breast milk MacGregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007:33 (2) 83 to 93
Acute migraine treatment while breastfeeding Paracetamol Drug of choice Aspirin Avoid, risk of Reyes Syndrome NSAID Very low concentration in breast milk Anti-emetics wide variety of agents recommend domperidone ( preferred to metoclopramide) Ergotamine Avoid as may inhibit lactation MacGregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007:33 (2) 83 to 93
Safety profile for preventative medication
Conclusion 1 Understand the patient journey Understand the patients psychosocial journey Understand the impact of the headache to the patient their friends and family work Adopt a holistic approach to care Involve the patient in the decision making Optimise acute treatment Offer flexibility Balance of benefits against side effects Minimise the number of headache days
Conclusion - 2 Optimise preventative medication The goal is to reduce the number of headache days with the fewest side effects at the lowest dose Different headaches need different preventative drugs Different patients respond to different drugs and dosages Finding the right drug and the right drug dose takes time and persistence start low build slow use for at least 3 months to assess response
Conclusion - 3 If hormones are relevant core principles apply Adopt a holistic approach to care Involve the patient in the decision making Risk needs to be discussed Optimise acute treatment Consider standard prophylaxis options Hormonal manipulation may not suit everybody risks need to be discussed and considered