What are the guidelines for newer medications, such as calcitonin gene-related peptide (CGRP) inhibitors, in the management of migraines?

Guidelines for Newer Medications in Migraine Management

For the management of migraines, CGRP antagonists (gepants) and monoclonal antibodies should be used as second or third-line treatments after traditional first-line therapies have failed or are not tolerated. 1

Acute Treatment of Episodic Migraine

First-Line Treatment

• Start with acetaminophen (650-1000 mg) for mild to moderate migraine attacks 1, 2
• For patients who don't respond adequately to acetaminophen alone:
  • Add a triptan to acetaminophen for moderate to severe attacks 1
  • Triptan + NSAID combination is most effective for moderate to severe attacks 2

Second/Third-Line Treatment (CGRP Antagonists-Gepants)

• Consider rimegepant, ubrogepant, or zavegepant when:
  • Patient has inadequate response to first-line treatments
  • Patient has contraindications to triptans (cardiovascular disease)
  • Patient experiences intolerable side effects from first-line treatments 1

Preventive Treatment of Episodic Migraine

First-Line Prevention

• Beta-adrenergic blockers (metoprolol or propranolol)
• Antiseizure medication (valproate)
• Serotonin and norepinephrine reuptake inhibitor (venlafaxine)
• Tricyclic antidepressant (amitriptyline) 1

Second-Line Prevention (CGRP-Related Medications)

• CGRP antagonists-gepants:
  • Atogepant or rimegepant 1
• CGRP monoclonal antibodies:
  • Eptinezumab, erenumab, fremanezumab, or galcanezumab 1, 3, 4

Third-Line Prevention

• Antiseizure medication (topiramate) if patient doesn't tolerate or respond to first and second-line treatments 1

CGRP Antagonist Specifics

CGRP Monoclonal Antibodies

1. Fremanezumab (Ajovy)

   • Dosing: 225 mg monthly OR 675 mg quarterly (as three consecutive 225 mg injections)
   • Administration: Subcutaneous injection in abdomen, thigh, or upper arm
   • Contraindications: Serious hypersensitivity to fremanezumab or excipients
   • Common adverse effects: Injection site reactions 3

2. Erenumab (Aimovig)

   • Dosing: 70 mg once monthly; some patients may benefit from 140 mg once monthly
   • Administration: Subcutaneous injection in abdomen, thigh, or upper arm
   • Contraindications: Serious hypersensitivity to erenumab or excipients
   • Common adverse effects: Injection site reactions, constipation, hypertension 4

Clinical Considerations for CGRP Antagonists

Benefits

• Significantly reduce average number of migraine days in both episodic and chronic migraine sufferers 5, 6
• May be more effective than traditional preventives for some patients 7
• Alternative for patients with contraindications to triptans 8

Potential Concerns

• Higher cost compared to traditional migraine medications 1
• Limited long-term safety data 7
• Patient preference considerations: oral treatments generally preferred over injectables 1
• Potential for systemic effects due to CGRP's role in multiple physiological processes 7

Common Pitfalls in CGRP Antagonist Use

• Cost considerations: CGRP antagonists-gepants and monoclonal antibodies are significantly more expensive than traditional migraine medications 1
• Duration of trial: Allow sufficient time (3-4 months) for preventive medications to reach maximal efficacy 2
• Monitoring: Regular assessment for hypersensitivity reactions, which can occur from hours to more than a week after administration 4
• Special populations: Use caution in patients with cardiovascular risk factors, as CGRP has vasodilatory effects 7

Decision Algorithm for CGRP Antagonist Use

1. For acute treatment:

   • Try acetaminophen ± triptan first
   • Consider CGRP antagonist-gepant if inadequate response or contraindications to triptans

2. For preventive treatment:

   • Start with beta-blocker, valproate, venlafaxine, or amitriptyline
   • If inadequate response or intolerance, try CGRP antagonist-gepant or CGRP monoclonal antibody
   • Consider topiramate if both first and second-line treatments fail

3. Selection factors between CGRP options:

   • Patient preference for administration route (oral vs. injectable)
   • Frequency of dosing (monthly vs. quarterly injections)
   • Insurance coverage and cost considerations
   • Comorbid conditions (avoid erenumab in patients with constipation or hypertension)