Elevated Saliva Calcitonin Gene-Related Peptide Levels During Acute Migraine Predict Therapeutic Response to Rizatriptan


Objectives: (1) To measure calcitonin gene‐related peptide (CGRP) levels in the saliva of individuals with migraine during the premonitory period, mild headache, moderate to severe headache, and post‐resolution phases as compared with baseline (interictal) CGRP levels. (2) To correlate response to rizatriptan administered during moderate headache with levels of CGRP levels measured in saliva.

Background: CGRP is implicated in the underlying pathophysiology of migraine. To date no study has measured changes of saliva CGRP through the clinical evolution of a migraine attack and correlated saliva CGRP levels to clinical response to therapy.

Methods: Data were summarized using tables and descriptive statistics. Statistical analysis was performed with the non‐parametric signed‐rank test using Minitab15 statistical software. Results of statistical analyses were considered significant at P < .05. Responding subjects were defined as those who were symptom free at the time of the last collected saliva sample and did not have to rescue. Non‐responding subjects were defined as those who rescued with an additional dose of rizatriptan or another medication or who were not symptom free at the end of the collection period.

Results: Statistically significant elevations of CGRP were noted in the premonitory, mild headache, and moderate to severe headache phase of the migraine compared with baseline (interictal) levels. A better therapeutic response to rizatriptan was observed in subjects with elevated saliva CGRP levels. Successful treatment with rizatriptan correlated with saliva CGRP levels returning to near baseline levels. In the rizatriptan non‐responder group, no significant change in saliva CGRP levels was found at any phase of the migraine attack.

Conclusions: Elevation of saliva CGRP is predictive of responsiveness to rizatriptan. In the rizatriptan responsive population, CGRP levels are elevated beginning with the premonitory period and throughout mild and moderate/severe headache. Successful response to rizatriptan correlated with return of saliva CGRP levels to near baseline (interictal) values.



Document Type





calcitonin gene‐related peptide, migraine, pathophysiology, rizatriptan, saliva, headache phase

Publication Date


Journal Title

Headache: The Journal of Head and Face Pain