Preventive migraine therapies are used to reduce duration, frequency, and severity of attacks, the need for acute treatment, and overall headache disability.26 Medications typically are chosen based on efficacy, adverse effect profile, and patient comorbidities. Barriers to successful use include poor patient adherence and tolerability, the need for slow dose titration, and long-term use (minimum of 2 months) at maximum tolerated or minimum effective doses. Medications with established efficacy (Level Aa) based on the 2012 guidelines from the American Academy of Neurology (AAN) and the AHS are given in TABLE 5.27-29
Drugs having received the strongest level of evidence for migraine prevention are metoprolol, propranolol, timolol, topiramate, valproate sodium, divalproex sodium, and onabotulinumtoxinA (Botox), and frovatriptan for menstrual migraine prevention.Because these guidelines were last updated in 2012, they did not cover gepants (which will be discussed shortly). The AHS released a position statement in 2019 supporting the use of anti-CGRP monoclonal antibodies (mAbs) in those who cannot tolerate or have had an inadequate response to a 6-week trial of at least 2 AAN/AHA Level A or Bb treatments.10 No head-to-head trials exist between non-CGRP preventive therapies and the CGRP antagonists.
CGRP-targeted prevention
Four anti-CGRP mAbs and 2 gepants have been approved for migraine prevention in the United States. Differences between products include targets (ligand vs receptor), antibody IgG subtype, bioavailability, route of administration, and frequency of administration.28 As noted in the Phase 3 studies (TABLE 619,30-47), these therapies are highly efficacious, safe, and tolerable.
Gepants. Rimegepant, discussed earlier for migraine treatment, is one of the CGRP receptor antagonists approved for prevention. The other is atogepant (Qulipta), approved only for prevention. Ubrogepant is not approved for prevention.
Anti-CGRP mAb is the only medication class specifically created for migraine prevention.10,26 As already noted, several efficacious non-CGRP treatment options are available for migraine prevention. However, higher doses of those agents, if needed, can lead to intolerable adverse effects for some patients, thereby limiting overall efficacy. Anti-CGRP mAbs, a targeted, highly efficacious treatment option, offer efficacy comparable to non-CGRP agents with a more favorable adverse effect profile for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.10
