Migraine

Prescribing Notes:

• Lifestyle advice for patients with migraine includes reinforcing the importance of maintaining a regular routine: encouraging regular meals, adequate hydration with water, sleep and exercise. Avoid specific triggers if known. Consider activities that encourage relaxation such as mindfulness, yoga or meditation.
• Migraine treatment should be selected for each patient according to severity and frequency of attacks, other symptoms, patient preference and treatment history.
• A stepped stratified approach should be used for treatment of an acute attack starting with an analgesic +/- antiemetic and escalating to 5HT1 receptor antagonist (triptan) as required. Combination therapy using a triptan and an NSAID may be considered. When starting acute treatment, healthcare professionals should warn patients about the risk of developing medication over-use headache.
• When medication over-use is identified it should be addressed, refer to SIGN 155 Pharmacological Management of Migraine for guidance.
• The aim of prophylactic therapy is to reduce the frequency, severity and duration of attacks and improve responsiveness to treatment.
• All women of childbearing potential should be advised of potential of foetal malformations with migraine prophylactic medications. Ensure that risks during pregnancy are explained and the importance of using adequate contraception.

Prescribing Notes:

• Treatment should be given as soon as possible after onset of migraine headache.
• Simple oral analgesics such as aspirin, ibuprofen, or paracetamol are suitable first line agents. This medication is better taken early in the attack when absorption will be least inhibited by gastric stasis.
• A further dose of simple analgesia may be repeated after initial dose, however, if this is not adequate then consider moving to next step of treatment. Repeated doses of simple analgesia are not beneficial in treatment of migraine headache.
• Antiemetic choices are discussed in the nausea and vomiting section of the formulary, please see the ‘Treatment of nausea and vomiting associated with migraine’ pathway.
• Chronic overuse of aspirin, NSAIDS and paracetamol (use on >15 days/month), particularly in combination with codeine, may cause medication overuse headache. Combination analgesics should therefore be avoided.

Prescribing Notes:

General Notes on Triptans

• The evidence base to guide the selection of alternative oral triptans if sumatriptan is not tolerated or ineffective is limited. The following recommendations are based on local opinion, available evidence on cost effectiveness, comparative efficacy, safety and patient acceptability.
• If a patient fails to respond to one triptan which has been tried for three separate migraine attacks, then an alternative triptan should be considered.
• Recommendations for alternative oral triptans if sumatriptan is not tolerated or ineffective:
  
  • If sumatriptan is ineffective rizatriptan can be considered.
  • If side effects of sumatriptan are troublesome almotriptan can be considered.
  • In severe migraine eletriptan can be considered.
• Ensure diagnosis of migraine is correct. Triptans are expensive and may not be effective in other types of headache.
• Medication should be taken as early as possible after migraine headache starts, even if this is during the aura phase. Headache recurrence within the first 24 hours can be treated with a second dose. If the first dose of a triptan fails to help, alternative (analgesic) medication or route of administration should be considered.
• Overuse of triptans (more than 10 days/month) should be avoided due to the risk of medication overuse headache.
• Sumatriptan can be considered for treatment of acute migraine in pregnant women in all stages of pregnancy. The risks of medication overuse should be explained and the same limit of 10 days per month apply.

Third Choice Options

• In severe migraine or where vomiting precludes oral treatment or where oral triptans have been ineffective, consider nasal or subcutaneous triptans. Combination therapy using a triptan and an NSAID may be considered.
• Alternatively, rimegepant is approved for the acute treatment of migraine with or without aura in adults. Use is restricted for patients who have had inadequate symptom relief after trials of at least two triptans or in whom triptans are contraindicated or not tolerated; and have inadequate pain relief with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. 

Combination Therapy with Triptan and an NSAID

• If triptan therapy alone is not effective, combination therapy using a triptan and an NSAID should be considered. The combination should be taken simultaneously at the onset of migraine headache. The NSAID should be prescribed at a dose recommended for acute migraine treatment. SIGN 155 makes a specific recommendation to consider using sumatriptan 50-85mg and naproxen 500mg. NSAID options include aspirin, ibuprofen or naproxen.

Rectal or Parenteral NSAIDs

• Diclofenac suppositories may be considered where vomiting precludes oral treatment or other NSAIDs have been ineffective.
• Parenteral opiates should be avoided in migraine. Intramuscular diclofenac is preferred if parenteral analgesia is required.

Prescribing Notes:

General notes

• The aim of prophylactic therapy is to reduce the frequency, severity and duration of attacks and improve responsiveness to treatment. Patients should not expect to be completely headache free, but aim for a reduction of 50% in frequency of migraines.
• Slow titration of prophylactic therapy may improve tolerability and minimise side effects.
• Prophylaxis should be given for 8 weeks at the target doses if tolerates to adequately assess its efficacy.
• Patients should be defined as having episodic or chronic migraine using headache diaries. Headache diaries to continue through treatment to aid in review and assessment of efficacy.
• Chronic migraine: 15 headache days per month, of which 8 must be migraine.
• Episodic migraine: 14 or less headache days per month (high frequency episodic migraine 10-14 days per month).
• Refer to local board guidance. In NHS Lothian refer to RefHelp.

Migraine prophylaxis in women of child-bearing potential

• All women of childbearing potential should be advised of potential of foetal malformations with migraine prophylactic medications. Ensure that risks during pregnancy are explained and the importance of using adequate contraception.
• For more information on the cautions of use of migraine prophylactic medications in pregnancy refer to national guidelines “National Headache Pathway - Migraine during pregnancy and following childbirth” which can be found here  NHS Scotland: National Headache Pathway, the BNF, and product literature. 
• Amitriptyline, candesartan, and propranolol are treatment options in individuals of childbearing potential. Candesartan must not be used for migraine in pregnancy or in those planning pregnancy. Appropriate information should be given and/or action taken to prevent the risk of exposure during pregnancy. Candesartan may adversely affect foetal and neonatal blood pressure control and renal function; neonatal skull defects and oligohydramnios have also been reported.

Amitriptyline

• Amitriptyline may be particularly useful if there is co-existent sleep disturbance and/or tension type headache. In patients who cannot tolerate amitriptyline, a less sedating tricyclic antidepressant should be considered.

Propranolol

• Evidence suggests that standard release preparations of propranolol are superior to modified release preparations.
• Prescribers should be aware of the risk of propranolol in overdose, which can be potentially toxic and lead to seizures and death.

Topiramate

• Topiramate is recommended as a prophylactic treatment for patients with episodic or chronic migraine.
• Topiramate is contraindicated in pregnancy and in any individual of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. This follows a review by the MHRA which concluded that the use of topiramate during pregnancy is associated with significant harm to the unborn child. Harms included a higher risk of congenital malformation, low birth weight and a potential increased risk of intellectual disability, autistic spectrum disorder and attention deficit hyperactivity disorder in children of mothers taking topiramate during pregnancy. 
• See MHRA guidance topiramate safety measures. 
• To obtain risk materials including pregnancy prevention materials for a specific brand of topiramate, see external links to the eMC (SPC & patient leaflets) found next to the medicines choices above or access the eMC website topiramate search and click on “Risk Materials” next to that medicine.
• Topiramate has been associated rarely with serious eye reactions. If raised intra-ocular pressure occurs then seek specialist ophthalmological advice and stop topiramate as rapidly as is feasible. Appropriate measures should be used to reduce intra-ocular pressure. Patients should be advised to report any change in vision or onset of eye pain after commencing topiramate.

Other prophylactic migraine treatments

• Flunarizine is often well tolerated. Depression is a possible side effect, so it should be used with caution in patients with depression.
• Pizotifen is lacking in evidence as a preventative therapy for migraine but is widely used.
• Frovatriptan (2.5mg twice daily) should be considered as a prophylactic treatment in women with perimenstrual migraine from two days before until three days after bleeding starts.
• For advanced therapies see the pathway for Advanced therapies for treatment of chronic and episodic migraine.

Prescribing Notes:

Oral calcitonin gene-related peptide (CGRP) inhibitors

• Atogepant (Aquipta) is approved for the prophylaxis of migraine in adults who have at least 4 migraine days per month. Restricted to use for patients with chronic and episodic migraine who have had prior failure on three or more migraine preventive treatments. Chronic migraine is defined as 15 headache days per month, of which 8 must be migraine. Episodic migraine is defined as 14 or less headache days per month (high frequency episodic migraine 10-14 days per month).
• Chronic migraine patients may be offered Botox prior to atogepant if available.
• Rimegepant is approved for the preventive treatment of episodic migraine in adults. Restricted to use for patients with episodic migraine who have at least 4 migraine attacks per month, but fewer than 15 headache days per month and who have had prior failure on three or more migraine preventive treatments. Episodic migraine is defined as 14 or less headache days per month (high frequency episodic migraine 10-14 days per month).
• In NHS Lothian refer to RefHelp Migraine/Chronic headache guidelines for additional prescribing information for primary care prescribers.  
• Refer to the guidance covered in the National Headache Pathway - Headache Prophylaxis / Treatment advice which can be found here  NHS Scotland: National Headache Pathway 
• Support in relation to prescribing can be provided via email communication with local specialists if needed. 

Botulinum A toxin 

• Botulinum A toxin (Botox) is accepted for restricted use for the prophylaxis of headaches in adults with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine). Restricted to use in adults with chronic migraine whose condition has failed to respond to ≥3 prior oral prophylactic treatments, where medication overuse has been appropriately managed.

Parenteral calcitonin gene-related peptide (CGRP) inhibitors

• Erenumab (Aimovig) is accepted for the prophylaxis of migraine in adults who have at least four migraine days per month. Restricted to use in patients with chronic migraine (defined as ≥15 headache days per month, of which ≥8 days were migraine days) and in whom at least three prior prophylactic treatments have failed. Refer to local protocol for prescribing guidance.
• Fremanezumab (Ajovy) is accepted for restricted use for the prophylaxis of migraine in adults who have at least four migraine days per month. Restricted for use in the treatment of patients with chronic and episodic migraine who have had prior failure on three or more migraine preventive treatments. Refer to additional local prescribing guidance.
• Galcanezumab (Emgality) is accepted for restricted use for the prophylaxis of migraine in adults who have at least 4 migraine days per month. Restricted for use for the treatment of patients with chronic and episodic migraine who have had prior failure on three or more migraine preventive treatments. Refer to additional local prescribing guidance.

Prescribing Notes:

• Lifestyle advice for patients with migraine includes reinforcing the importance of maintaining a regular routine: encouraging regular meals, adequate hydration with water, sleep and exercise. Avoid specific triggers if known. Consider activities that encourage relaxation such as mindfulness, yoga or meditation.
• Migraine treatment should be selected for each patient according to severity and frequency of attacks, other symptoms, patient preference and treatment history.
• A stepped stratified approach should be used for treatment of an acute attack starting with an analgesic +/- anti-emetic and escalating to 5HT1 receptor antagonist (triptan) as required. Combination therapy using a triptan and an NSAID may be considered. When starting acute treatment, healthcare professionals should warn patients about the risk of developing medication over-use headache.
• When medication over-use is identified it should be addressed, refer to SIGN 155 Pharmacological Management of Migraine for guidance.
• Migraine prophylaxis should be considered in patients with attacks occurring more than four times per month, or when less frequent attacks are particularly severe and prolonged and interfere with their daily routine. The aim of prophylactic therapy is to reduce the frequency, severity and duration of attacks and improve responsiveness to treatment.
• All females of childbearing potential should be advised of potential of foetal malformations with migraine prophylactic medications. Ensure that risks during pregnancy are explained and the importance of using adequate contraception.

Abdominal Migraine

• Common triggers for abdominal migraine attacks include stressors (family and/or education), poor sleep pattern, lack of regular routine for food/meals/hydration, and lifestyle advice includes reinforcing the importance of maintaining a regular routine: encouraging regular meals, adequate hydration with water, sleep and exercise. Specific triggers, if known, should be avoided.
• Diagnosis of abdominal migraine should be clear and follow the Rome IV criteria (including severe abdominal pain lasting at least for an hour which significantly restricts activities with a recurring pattern). Anorexia, nausea and vomiting, pallor, headache and photophobia are specific associated symptoms. Episode occurrence of at least 2 episodes over a 6-month period, with symptom free period supports diagnosis.
• Treatment of abdominal migraine is focussed on prevention of the episodes of migraine and includes non-pharmacological approaches. Life-style advice, precedes pharmacological therapies, as the initial step to managing abdominal migraine.

Prescribing Notes:

• Round doses to a measurable volume or nearest tablet where appropriate.
• Treatment should be given as soon as possible after onset of migraine headache.
• Ibuprofen and paracetamol can be given in combination.
• A further dose of simple analgesia may be repeated after initial dose, however, if this is not adequate then consider moving to next step of treatment. Repeated doses of simple analgesia are not beneficial in treatment of migraine headache.
• Anti-emetic choices are discussed in the nausea and vomiting section of the formulary, please see the ‘Treatment of nausea and vomiting associated with migraine’ pathway.
• Anti-emetic may be effective given alone, if first doses of simple analgesia have not been effective.
• Sumatriptan may be added in to with either ibuprofen or paracetamol or given as monotherapy if that is the only suitable medication.

Prescribing Notes:

• There is limited experience with sumatriptan and it is therefore not recommended in children under 12 years old except on specialist advice.
• NICE clinical guideline 150, favours the use of sumatriptan nasal spray over tablets in children due to poor oral absorption.
• Do not use triptans in hemiplegic migraine.
• Ibuprofen + sumatriptan + prochlorperazine can be used in combination.
• Consider an anti emetic in addition to other acute treatment for migraine even in the absence of nausea and vomiting.
• Ensure diagnosis of migraine is correct. Triptans may not be effective in other types of headache.
• Medication should be taken as early as possible after migraine headache starts, even if this is during the aura phase. Headache recurrence within the first 24 hours can be treated with a second dose. If the first dose of a triptan fails to help, alternative (analgesic) medication or route of administration should be considered.
• Overuse of triptans (more than 10 days/month) should be avoided due to the risk of medication overuse headache.

Combination Therapy with Triptan and an NSAID

• If triptan therapy alone is not effective, combination therapy using a triptan and an NSAID should be considered. The combination should be taken simultaneously at the onset of migraine headache. The NSAID should be prescribed at a dose recommended for acute migraine treatment.

Prescribing Notes:

• Migraine prophylaxis is justified for attacks affecting quality of life such as those necessitating time off school.
• Migraine prophylaxis in patients < 12 years is prescribed following specialist advice.
• Migraine prophylaxis with propranolol or pizotifen for patients > 12 years can be commenced in general practice; migraine prophylaxis with topiramate or amitriptyline is specialist initiation.
• Amitriptyline can be considered for migraine prophylaxis in children > 12 years.
• The choice of prophylactic agent will depend on individual patient factors - i.e. pizotifen may be preferred over propranolol in children who are physically active.
• Prescribers should be aware of the risk of propranolol in overdose, which can be potentially toxic and lead to seizures and death.
• Propranolol should be avoided in children with a history of asthma or bronchospasm.
• Evidence suggests that standard release preparations of propranolol are superior to modified release preparations.
• Topiramate can be a useful alternative in some patients, prescribed on specialist advice.
• Topiramate is contraindicated in pregnancy and in any individual of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. This follows a review by the MHRA which concluded that the use of topiramate during pregnancy is associated with significant harm to the unborn child. Harms included a higher risk of congenital malformation, low birth weight and a potential increased risk of intellectual disability, autistic spectrum disorder and attention deficit hyperactivity disorder in children of mothers taking topiramate during pregnancy. 
• See MHRA guidance topiramate safety measures. 
• To obtain risk materials including pregnancy prevention materials for a specific brand of topiramate, see external links to the eMC (SPC & patient leaflets) found next to the medicines choices above or access the eMC website topiramate search and click on “Risk Materials” next to that medicine. 
• The need for continuing prophylaxis should be reviewed after 6 months of starting treatment.

General notes

• The aim of prophylactic therapy is to reduce the frequency, severity and duration of attacks and improve responsiveness to treatment. Patients should not expect to be completely headache free but aim for a reduction of 50% in frequency of migraines.
• Migraine prophylaxis should be considered in patients with attacks occurring more than four times per month, or when less frequent attacks are particularly severe and prolonged and interfere with their daily routine.
• Slow titration of prophylactic therapy may improve tolerability and minimise side effects.
• Prophylaxis should be given for 8 weeks at the target doses if tolerates to adequately assess its efficacy.

Migraine prophylaxis in any individual of child-bearing potential

• All women of childbearing potential should be advised of potential of foetal malformations with migraine prophylactic medications. Ensure that risks during pregnancy are explained and the importance of using adequate contraception.

Prescribing Notes:

• Step one of treatment is to treat early to abort attack of abdominal migraine.
• Round doses to a measurable volume or nearest tablet where appropriate.
• Treatment should be given as soon as possible after onset of abdominal migraine.
• Ibuprofen and paracetamol can be given in combination.
• A further dose of simple analgesia may be repeated after initial dose, however, if this is not adequate then consider moving to next step of treatment.
• Antiemetic may be effective given alone, if first doses of simple analgesia have not been effective.

Prescribing Notes:

• There is limited experience with sumatriptan and it is therefore not recommended in children under 12 years old except on specialist advice.

Prescribing Notes:

• Non-pharmacological prophylaxis (lifestyle, environmental, known triggers) should be considered as part of the treatment plan.
• Propranolol should be avoided in children with a history of asthma or bronchospasm.
• Prescribers should be aware of the risk of propranolol in overdose, which can be potentially toxic and lead to seizures and death.
• Prescribers should be aware of recent increases in propranolol overdoses and consider patients risk factors before prescribing.
• The need for continuing prophylaxis should be reviewed after 6 months of starting treatment.
• All females of childbearing potential should be advised of potential of foetal malformations with migraine prophylactic medications. Ensure that risks during pregnancy are explained and the importance of using adequate contraception.

Prescribing Notes:

• Lifestyle advice for patients with migraine includes reinforcing the importance of maintaining a regular routine: encourage regular meals, adequate hydration with water, sleep and exercise. Avoid specific triggers if known. Consider activities that encourage relaxation such as mindfulness, yoga or meditation.
• Frequency and intensity of migraines may diminish during pregnancy.
• SIGN 155 - Pharmacological management of migraine states that opioid analgesics should not be used routinely in the management of patients with acute migraine due to the potential for development of medication overuse headache.
• For the appropriate supply of sumatriptan in the management of migraine see RPS Guidance on OTC Sumatriptan.