Detailed information about triptans in migraine and second line treatments

• triptans work by selectively stimulating 5-hydroxytriptamine 1 (5HT1) receptors in the brain (1)
  
  
• when prescribing acute treatments there are two broad strategies:
  1. Stepped approach: start with simple analgesics and if ineffective step-up e.g. to a triptan
  2. Stratified approach: target treatment based on attack severity
     • the stratified approach is associated with better health related outcomes and lower indirect costs (e.g. GP and hospital visits)
       
       
• adding an anti-emetic to an acute treatment improves efficacy unrelated to nausea and/or vomiting and can improve gastric motility and hence drug absorption (3)
  
  
• the end point of an effective treatment is a significant response at two hours, because the natural history for most attacks is to spontaneously improve in 4 hours (3)
  
  
• if a treatment is not effective at 2 hours, then it is unlikely to work in that attack at that dose and considering an alternative acute treatment or combination treatment would be reasonable (3)
  
  
• lack of response to one triptan does not predict response to other triptans (2,3)
  
  
• triptans are most effective when taken early in the headache phase of the attack (2,3)
  
  
• triptans are less likely to be effective at treating the headache if taken during the preceding aura (2,3)
  • unlike symptomatic therapy, triptans should not be taken too early
  • is evidence of greater efficacy when taken whilst pain is still mild, but triptans appear to be ineffective if administered before the headache has developed (eg, during aura)
    
    
• contraindications to triptans include ischaemic heart disease, cerebrovascular disease, previous myocardial infarction, and uncontrolled or severe hypertension. The cardiovascular risk of triptans is very low in the absence of these contra-indications (2,3)
  
  
• after 2 treatment failures with a particular triptan a trial with an alternative triptan is recommended. This rationale is based on the finding that in patients who experienced treatment failure in two attacks, 70% failed to respond in the third attack. Around 30% patients do not respond to any triptan (3)
  
  
• acute treatments can be associated with the development of medication overuse headache (3)
  
  
• opioids are not recommended for the treatment of acute headache because of the significant risk of medication overuse and the most protracted withdrawal (3)
  
  
• for patients attending the emergency department parenteral NSAIDs or subcutaneous sumatriptan should be considered, and evidence also supports the use of antiemetics. Opioids have not been shown to be significantly effective and should not be used

Prescribe the standard starting dose of oral sumatriptan (50 mg):

• sumatriptan is the longest established triptan, and consequently has the most clinical experience attached to
  • is often used as the higher dose of sumatriptan (100 mg)

When considering the response to treatment with oral sumatriptan (2):

• sumatriptan 6 mg subcutaneous remains the most rapid and effective treatment for pain relief but has a higher risk of adverse events than other formulations
• combination of a triptan and an NSAID with a long half-life, such as naproxen, is better than monotherapy
• in comparison to sumatriptan 100 mg:
  • lower adverse events: naratriptan 2.5 mg, almotriptan 12.5 mg and frovatriptan 2.5 mg
    
    
  • better 2-hour pain response: eletriptan 80 mg and rizatriptan 10 mg, almotriptan 12.5 mg
    
    
  • lower recurrence rate: frovatriptan 2.5 mg, and eletriptan 40 mg

Notes:

• ergotamine has largely been superseded by the 5HT1 agonists (4)
  • ergotamine tartrate 1-2mg, in clinical trials in which it has been used as a comparator, has shown significantly lower relapse rates which may be due to its prolonged duration of action
  • toxicity and misuse potential are greater risks with ergotamine than with triptans
  • has very poor bioavailability and is better taken rectally
  • should not be taken concomitantly with any triptan
  • NICE however advise " Do not offer ergots or opioids for the acute treatment of migraine"
• dexamethasone in acute migraine
  • when added to standard abortive migraine therapy, single dose parenteral dexamethasone is associated with a 26% relative reduction in recurrent headache (NNT=9) occurring within 72 hours
  • a meta-analysis concluded that adding dexamethasone to standard therapy reduces short-term relapse of migraine (5)

Reference:

• 1. Drug and Therapeutics Bulletin 1998; 36(6):41-4.
• 2. British Association of the Study of Headache (BASH) guidelines, 2019
• 3. Migraine. https://headache.org.uk/ (Accessed 19/3/23)
• 4.BMJ. 2008 Jun 14;336(7657):1359-61.
• 5. Singh A et al. Does the Addition of Dexamethasone to Standard Therapy for Acute Migraine Headache Decrease the Incidence of Recurrent Headache for Patients Treated in the Emergency Department? A Meta-analysis and Systematic Review of the Literature. Acad Emerg Med. 2008 Oct 25.
• 5.NICE (December 2021). Headaches - Diagnosis and management of headaches in young people and adults