Etoricoxib and celecoxib sensitive indomethacin‐responsive headache disorders

Abstract

Indomethacin-responsive headaches include paroxysmal hemicrania (PH) and hemicrania continua (HC), two of the disorders within the group termed the trigeminal autonomic cephalalgias, and other primary headache disorders, such as primary stabbing headache (PSH), primary cough headache (PCH), and primary headache associated with sexual activity (PHASA). These headache syndromes differ in clinical features and extent of response to indomethacin. 1 In the current International Classification of Headache Disorders, 3rd edition 2 an absolute response to indomethacin is mandatory to diagnose PH and HC. Although not a diagnostic criterion for PCH, PHASA, or PSH, indomethacin is the most consistently reported preventative effective for these paroxysmal and usually short-lived headaches. 1,3,4 Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that acts as a reversible inhibitor of prostaglandin-forming cyclooxygenase (COX), inhibiting COX-1 and COX-2 isoforms, with greater selectivity for the former. 5 The drug has been demonstrated to penetrate the blood-brain barrier in vivo using rat brain perfusion technique, thus rendering indomethacin able to target mechanisms within the central nervous system. 6 A potential nitrergic mechanism of action for indomethacin has been postulated given that indomethacin has been demonstrated to inhibit nitric oxideinduced dural vasodilation using the in vivo technique of intravital microscopy in rats. 7 Indomethacin may thus have a role in modulating cerebral vasodilatory prostaglandin production, although the defined mechanism of action relevant to indomethacin-responsive headaches is yet to be elucidated.Most patients show a rapid therapeutic response to indomethacin but, despite concomitant gastroprotection, intolerability limits its use. Unfortunately, there remain limited satisfactory alternatives. 1,8 Gastrointestinal adverse effects are the main complications ranging from dyspepsia to life-threatening gastrointestinal bleeding.Other adverse effects include effects on blood pressure, cardiovascular, hepatic and renal dysfunction, and platelet inhibition. 9 Central nervous system adverse effects, such as dizziness and drowsiness, are also commonly reported. 10

Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment

“…Although some individuals respond to other NSAIDs with COX-I inhibitory properties, the response to indometacin remains the most consistent. The selective COX-II inhibitors can also be effective (27)(28)(29), thus COX-inhibition is unlikely to answer the selective indometacinresponsiveness.…”

“…There was no response seen with carbamazepine, amitriptyline, supra-orbital and greateroccipital nerve blocks. Also reported for at least five cases per drug group are responses to the COX-II inhibitors, refocoxib, celecoxib and etoricoxib (27,28,(62)(63)(64).…”

“…Although some individuals respond to other NSAIDs with COX-I inhibitory properties, the response to indometacin remains the most consistent. The selective COX-II inhibitors can also be effective (27–29), thus COX-inhibition is unlikely to answer the selective indometacin-responsiveness. Calcitonin-gene-related peptide (CGRP), which has been shown to be elevated during an attack in PH, normalised following treatment with indometacin (30).…”

“…Other primary headaches have also been reported with PH, either occurring simultaneously or independently and include cough headache (43,56,57), trigeminal neuralgia (so-called PH-Tic) (58,59) and SUNHA. In these cases the PH responded to indometacin, the trigeminal neuralgia responded to carbamazepine and the SUNHA responded to lamotrigine (27). The responses for each syndrome were independent, in that treatment of one did not have an impact on any comorbid headache syndrome.…”

“…In those not tolerant of indometacin, most frequently reported benefit is with other non-steroidal anti-inflammatory drugs (NSAIDs) including the COX-II inhibitors refecoxib, celecoxib and etoricoxib (27,64). Refecoxib was withdrawn because of an increased risk of cardiovascular disease.…”