Objective:

To evaluate the safety and efficacy of CGRP antagonists for preventive management of cluster headaches by synthesizing data from randomized controlled trials (RCTs) and single-arm trials, highlighting their differences.

Key Findings:

• CGRP antagonists show promise in reducing the frequency of cluster headache attacks, with a significant percentage of participants achieving a ≥ 50% reduction.
• Safety profiles indicate manageable treatment-emergent adverse events, with specific rates to be included.
• Efficacy outcomes demonstrate a significant proportion of participants achieving meaningful reductions in attack frequency.

Interpretation:

CGRP antagonists may provide a new mechanism-based preventive treatment option for cluster headaches, with favorable safety and efficacy profiles.

Limitations:

• Limited number of rigorous RCTs specifically targeting cluster headaches, which may affect the reliability of the findings.
• Variability in study designs, populations, and dosing among included trials, which complicates the synthesis of results.

Conclusion:

CGRP antagonists represent a potentially effective preventive treatment for cluster headaches, warranting further investigation in larger, more standardized trials to confirm efficacy and safety.