Ditans in Migraine

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Mechanism of Action:

  • Ditans are selective 5-HT1F receptor agonists.
  • Unlike triptans, they do not cause vasoconstriction due to the absence of 5-HT1B/1D receptors on blood vessels.
  • Rationale: The 5-HT1F receptor is located in the central and peripheral nervous system, not on vasculature, avoiding vascular side effects.
  • Clinical Efficacy:
  • Lazertibant (first FDA-approved ditan) demonstrated superiority over placebo in phase 3 trials for acute migraine treatment.
  • Rationale: Efficacy was established in large, randomized controlled trials (RCTs) with statistically significant pain freedom and pain relief at 2 hours.
  • Adverse Effects:
  • Generally well-tolerated; common side effects include paresthesia, dizziness, and nausea.
  • Rationale: Lack of vasoconstrictive properties reduces cardiovascular risks seen with triptans.
  • Role in Therapy:
  • Preferred for patients with cardiovascular risk factors or contraindications to triptans.
  • Rationale: Avoids vasoconstriction-related complications (e.g., coronary artery spasm).
  • Key Differences from Triptans:
  • No vascular effects, broader therapeutic window, and potential for better tolerability.
  • Rationale: 5-HT1F receptor activation may modulate pain pathways without vascular changes.