Indomethacin testing in suspected paroxysmal hemicrania and hemicrania continua: Clinical phenotypes and response patterns in a tertiary headache centre

Abstract Background Indomethacin responsiveness is considered the defining diagnostic feature of hemicrania continua and paroxysmal hemicrania. However, the clinical presentation of indomethacin-responsive headaches is often heterogeneous, and practical guidance regarding which patients should undergo an indomethacin trial, the optimal duration of treatment, and the interpretation of partial responses remains limited. Cases Eighteen patients underwent an indomethacin trial in our pain centre over the last year, of whom eleven (61%) achieved a positive response. Positive responders included patients ultimately diagnosed with probable or definite hemicrania continua ( n  = 6); and probable or definite paroxysmal hemicrania ( n  = 5), including secondary forms. Clinical presentations frequently departed from ICHD-3 criteria. Trigeminal autonomic symptoms were absent in several responders, while migrainous features were common. Attack duration in patients with paroxysmal hemicrania frequently exceeded the 30-min upper limit defined by ICHD-3, and some patients presented with pain characteristics suggestive of neuropathic disorders. The median time to a clinically meaningful response was 13 days for hemicrania continua (range 3–35 days) and 11 days for paroxysmal hemicrania (range 4–23 days). Most patients responded to 150 mg/day, although escalation to 225 mg/day or prolonged treatment exceeding four weeks was occasionally required. Seven patients had negative trials, leading to alternative diagnoses including migraine, cluster headache, SUNA, post-traumatic headache, and idiopathic mandibular neuropathy. Conclusions This case series illustrates the broad clinical spectrum of indomethacin-responsive headaches and highlights the limitations of relying exclusively on ICHD-3 criteria when selecting patients for an indomethacin trial. Clinical suspicion should remain broad, particularly in patients with strictly unilateral headaches, atypical trigeminal autonomic cephalalgias, or refractory unilateral primary headaches.