Purpose of review: The serotonergic system has long been linked to migraine but recent studies highlight how much is still unclear about this link. And recent data add to the uncertainty of where/how triptans act and why they are headache specific.
Recent findings: Markers of 5HT levels in the brains of migraine patients show no changes between attacks. Several recent meta-analyses show the most convincing data on genetic differences in the serotonergic system for 5HT transporters. Findings of additional triptan actions on peripheral trigeminovascular neurons and in the hypothalamus add more fuel to the debate on where these drugs act. A growing list of studies show efficacy of multiple triptans and other 5HT1b/1d agonists in preclinical models of nonheadache pain arguing for reevaluation of whether these drugs have efficacy in other pain states. Despite these issues, serotonergic drugs continue to be the gold standard for abortive agents with new members on the horizon (5HT1f agonists).
Summary: Given the clear efficacy of serotonergic drugs for migraine, continued study on the role of the endogenous 5HT system may lead to more novel therapies. And with the list of studies demonstrating efficacy triptans in models of nonheadache, clinical studies should address whether these drugs work for other types of pain.