What are the treatment options for migraines, including new medications?

New Migraine Medications

The newest migraine medications include CGRP pathway inhibitors (gepants like rimegepant, ubrogepant, and atogepant) and monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab), with the 2023 VA/DoD guidelines providing strong recommendations for CGRP monoclonal antibodies for prevention and weak recommendations for gepants for acute treatment. 1

CGRP Monoclonal Antibodies for Prevention

The most significant advancement in migraine prevention involves CGRP-targeting monoclonal antibodies, which received a "strong for" recommendation—the highest level of evidence in the 2023 guidelines. 1

First-Line Preventive Options

• Erenumab (AIMOVIG), fremanezumab, and galcanezumab are strongly recommended for prevention of both episodic and chronic migraine, representing the first "strong for" recommendation among newer migraine preventive agents 1

• Erenumab 70 mg or 140 mg subcutaneously once monthly reduces monthly migraine days by 1.4-1.9 days compared to placebo, with 43-50% of patients achieving ≥50% reduction in migraine frequency 2

• Galcanezumab 120 mg monthly (after 240 mg loading dose) reduces monthly migraine days by 1.9-2.0 days in episodic migraine and 2.1 days in chronic migraine compared to placebo 3

• Eptinezumab (intravenous formulation) received a "weak for" recommendation for prevention of episodic or chronic migraine, offering an alternative delivery method 1

Clinical Advantages

• These agents demonstrate efficacy within the first month of treatment, with sustained benefit over 3-6 months 3, 2

• The subcutaneous formulations allow for self-administration at home, improving convenience 3, 2

• Adverse events are generally mild, with injection site reactions being most common 3, 2

Gepants (CGRP Receptor Antagonists)

Acute Treatment

• Rimegepant and ubrogepant received "weak for" recommendations for short-term treatment of migraine, representing the first oral CGRP antagonists approved for acute use 1

• These agents demonstrated moderately robust and clinically significant effects with a number needed to treat of 13 for pain freedom at 2 hours 1

• Gepants offer an alternative for patients who cannot tolerate triptans or have cardiovascular contraindications to triptans 1

Preventive Use

• Atogepant received a "weak for" recommendation for prevention of episodic migraine, making it the first oral gepant approved for prevention 1

• Rimegepant has insufficient evidence for preventive use despite being studied for this indication 1

Ditans (5-HT1F Agonists)

• Lasmiditan received a "neither for nor against" recommendation due to its adverse effect profile, despite demonstrating robust benefit in pain freedom and pain relief at 2 hours 1

• The number needed to harm is only 4 for treatment-emergent adverse effects, and the medication carries driving restrictions due to CNS effects including dizziness and somnolence 1

• Lasmiditan represents a mechanistically distinct option from triptans, acting on 5-HT1F receptors without causing vasoconstriction 1

Positioning New Medications in Treatment Algorithm

For Acute Treatment

• Start with established first-line agents: triptans remain strongly recommended for moderate to severe migraine (NNT 3.2-3.5 for oral formulations, 2.1 for subcutaneous) 1

• Consider gepants (rimegepant or ubrogepant) when:

  • Triptans are contraindicated due to cardiovascular disease 1
  • Patient has failed multiple triptan trials 1
  • Patient experiences intolerable triptan side effects 1

• Avoid lasmiditan unless all other options have failed and patient can accommodate driving restrictions and CNS side effects 1

For Prevention

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) should be considered as first-line preventive therapy alongside traditional options like topiramate, propranolol, and valproate 1

• The choice between traditional preventives and CGRP antibodies depends on:

  • Comorbidities (beta-blockers for hypertension/anxiety, topiramate for obesity) 1
  • Prior treatment failures 1
  • Patient preference for injection vs. oral medication 1
  • Cost and insurance coverage considerations 1

• Atogepant offers an oral CGRP antagonist option for patients who prefer oral medication over injections 1

Critical Safety Considerations

• CGRP-targeting medications have not shown the cardiovascular concerns associated with triptans, making them suitable for patients with vascular risk factors 3, 2

• Long-term safety data beyond 12 months remain limited for these newer agents 3, 2

• Avoid combining multiple CGRP-targeting agents (e.g., gepant for acute treatment with CGRP antibody for prevention) without clear rationale, as safety data for this approach are lacking 1

Common Pitfalls

• Do not abandon proven therapies prematurely: triptans and traditional preventives remain highly effective and cost-efficient for most patients 1, 4

• Ensure adequate trial duration: CGRP antibodies require 2-3 months to demonstrate full efficacy 3, 2

• Monitor for medication overuse headache: even newer acute medications can cause rebound headache if used more than twice weekly 1, 5

• Cost considerations: newer agents are significantly more expensive than generic triptans and traditional preventives, which may limit access 1