INTRODUCTION: Migraine and cluster headache are challenging to manage, with no 
tailored preventive medications available. Targeting the calcitonin gene-related 
peptide (CGRP) pathway to treat these headaches may be the first focused 
therapeutic option to date, with the potential for promising efficacy.
METHODS: We systematically searched PubMed and clinicaltrials.gov for randomized 
controlled trials investigating the preventive potential of monoclonal 
antibodies against the CGRP pathway in the treatment of migraine and cluster 
headache.
RESULTS: The literature search returned a total of 136 records, of which 32 were 
eligible for review.
DISCUSSION: Clinical data from phase II and III trials of the four monoclonal 
antibodies targeting the CGRP pathway: Eptinezumab, erenumab, fremanezumab, and 
galcanezumab, collectively show a positive effect in the preventive treatment of 
episodic and chronic migraine. Multiple phase II and III trials are under way to 
further determine the efficacy and safety of this new drug class. It may be 
particularly important to assess the cardiovascular effects of long-term CGRP 
blockade. Phase III trials are also currently in progress for the preventive 
treatment of cluster headache.
CONCLUSION: Efficacy of anti-CGRP monoclonal antibodies spells a promising 
future for the many patients suffering from migraine, and possibly also for the 
smaller but severely-affected population with cluster headache.