Updated Canadian guidelines for prevention of episodic and chronic migraine

The Canadian Headache Society has issued a new version of the migraine prevention guidelines, updating the previous guidelines published in 2012. The 2024 guidelines incorporate newer agents including onabotulinumtoxinA, anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and oral CGRP antagonists (gepants). Guidance has also been added on the prevention of chronic migraine. Chronic migraine is currently defined as 15 or more headache days per month, with at least eight days having migrainous features or response to migraine-specific medications. Patients with moderate-frequency episodic migraine (MFEM) have four to seven migraine days per month, while those with high-frequency episodic migraine (HFEM) have eight or more migraine days/month, but less than 15 headache days/month. The 2024 guidelines are presented in two parts: evidence-based recommendations on migraine preventive therapies, and migraine prevention strategies based on expert consensus.Evidence-based recommendations on migraine preventive therapies Episodic migraine A strong recommendation (high certainty of evidence) was made for use of erenumab, propranolol, metoprolol, nadolol and amitriptyline. A strong recommendation (moderate certainty of evidence) was made for use of atogepant, eptinezumab, fremanezumab, galcanezumab, candesartan, butterbur and riboflavin. A strong recommendation (low certainty of evidence) was made for use of coenzyme Q10 and magnesium citrate.A weak recommendation (high certainty of evidence) was made for use of divalproex, flunarizine and pizotifen.A weak recommendation (moderate certainty of evidence) was made for topiramate, rimegepant and memantine.A weak recommendation (low certainty of evidence) was made for use of levetiracetam, venlafaxine, verapamil and lisinopril.A weak recommendation (very low certainty of evidence) was made for use of enalapril and melatonin.Onabotulinum toxin type A, feverfew, ginger, gabapentin and statins are not recommended for prevention of episodic migraine.Chronic migraineA strong recommendation (high certainty of evidence) was made for use of atogepant, erenumab, eptinezumab, fremanezumab, galcanezumab and onabotulinumtoxinA. A strong recommendation (moderate certainty of evidence) was made for use of propranolol.A weak recommendation (very low certainty of evidence) was made for use of topiramate.Migraine prevention strategies based on expert consensus Who should receive preventive treatment?Patients with ≥ 4 moderate or severe headache days/month not responding to acute medication.Patients with ≥ 8 headache days/month, even when acute medications are effective, as the risk of medication overuse headache (MOH) is increased in this group.Patients who have migraine attacks with a significant impact on their life, despite using acute medications and trigger management/lifestyle modification strategies. The number of migraine days may be ≤ 3 in these situations if the impact is severe.What constitutes an adequate preventive trial?Drugs should be continued at a target dose for at least two months for an adequate trial unless side effects make drug discontinuation necessary.Most patients receiving anti-CGRP monoclonal antibodies can be evaluated for response after three months. In patients with a history of treatment-resistant chronic migraine, the improvement might be subtle over the first three months and become more apparent and clinically significant over six months.Patients receiving onabotulinumtoxinA should have a minimum of two quarterly injections; three quarterly injections could be reasonable.When should preventive therapy be considered effective?Headache frequency or intensity is reduced by 50% or more, although a lower reduction in headache frequency may be worthwhile, particularly if the drug is well tolerated.Headache diaries (e.g., mobile application, paper diary) are important in evaluating treatment effectiveness.Reduction in headache intensity and migraine-related disability also need to be considered (see guidelines for details).How long should successful preventive therapy be continued?No randomized studies provide clear guidance on the optimal duration of migraine preventive treatments. A generalized approach is presented below, but may not be suitable for all patients; a longer duration of treatment may be particularly important for patients with a long history of chronic migraine.Conventional oral preventive drugs: Consider tapering off at 12 months, especially if patients have reverted to an infrequent episodic pattern of headache (ideally 4–6 headache days/month) with good control with acute therapies, no risk of MOH and minimal disability. If headaches or migraine symptoms recur as the dose is decreased or as the drug is discontinued, the dose should be increased again, or the drug restarted.OnabotulinumtoxinA or anti-CGRP monoclonal antibodies: Consider discontinuation based on patient preference, but only if there is an episodic pattern of migraine with very minimal disability for a period of at least 12 months. OnabotulinumtoxinA: Increase the interval between injections; if there is no worsening, the treatment can be stopped. There are no long-term safety concerns with onabotulinumtoxinA to warrant discontinuation in patients who want to continue. Anti-CGRP monoclonal antibodies: Increase the dosing interval and restart therapy if there is a worsening of attacks. Some evidence indicates that stopping anti-CGRP therapies leads to increased attacks; patients should be warned accordingly. Patients should also be monitored for the possibility of new onset hypertension or worsening of existing hypertension.What advice should be given to the patient with medication overuse when prevention is being considered?When preventive therapy is started, evaluate patients for the presence of medication overuse. Instruct them on the appropriate amount of medication to use monthly and the frequency of acute medication use.Withdrawal may only be necessary for some patients; starting preventive therapy may be adequate. Opioid- and barbiturate-induced MOH is more likely to occur, and may be less likely to respond to prevention. Tapering is recommended in these situations.The guidelines also provide further detail on chronic migraine overlapping with high-frequency episodic migraine, special considerations for anti-CGRP therapies, and when CGRP targeting agents (atogepant, eptinezumab, galcanezumab, erenumab, fremanezumab) should be used.The following clinical strategies for migraine prevention are also outlined:First-time strategy: Beta-blockers, candesartan, CGRP-blockers, OnabotulinumtoxinA, tricyclic (amitriptyline)Low side effect strategy: candesartan, magnesium citrate, riboflavin, coenzyme Q10, melatonin, erenumab, galcanezumab, fremanezumab, eptinezumab, atogepant; onabotulinumtoxinA in chronic migraine.Increased body mass index strategy: topiramate, atogepantHypertension strategy: propranolol, candesartan, nadolol, metoprololDepression/anxiety strategy: amitriptyline, venlafaxineRefractory patient strategy: See guidelines for detailsMigraine during pregnancy and lactation strategy: See guidelines for details.The guidelines include a two-page table summarizing the medication recommendations for migraine prevention. The table includes medication class, medication recommendations for prevention of episodic migraine and chronic migraine (with strength of recommendation and certainty of the evidence), drug dosage, adverse effects, and situations where caution is indicated. The authors note that it would be useful to have studies direct comparing older medications, such as amitriptyline or propranolol which have strong recommendations for use in the guidelines, with newer anti-CGRP therapies.Reference:Medrea I, Cooper P, Langman M, et al. Updated Canadian Headache Society migraine prevention guideline with systematic review and meta-analysis. Can J Neurol Sci 2024 November 7:1-23. Online ahead of print. (accessed November 14, 2024).

Updated Canadian guidelines for prevention of episodic and chronic migraine

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