Parenteral Indomethacin (The Indotest) in Cluster Headache

Abstract

The interval between indomethacin administration and clinical response may be extremely relevant in the assessment of chronic paroxysmal hemicrania (CPH) and other unilateral headache disorders like cluster headache (CH), with which CPH can be confounded. Indomethacin is inactive in CH; however, in some anecdotal reports in recent years, doubt has been cast on the ineffectiveness of indomethacin in CH. In this study, we have re-assessed the effect of indomethacin treatment in a group of 18 patients with episodic CH (three females and 15 males). From the day 8 of the active period, indomethacin 100 mg i.m. was administered every 12 h, for 2 consecutive days, in an open fashion. The mean daily attack frequency before the test (1.6 +/- 0.6) was not statistically different from that on day 1 (2.1 +/- 0.9) and day 2 (1.9 +/- 0.8) after indomethacin administration. The mean interval between indomethacin injection and the following attack (day 1 and day 2) was 4.6 + 1.1 h. We did not observe any refractory period in any patient after indomethacin. Since the 'expected' attack occurred when there theoretically could have been a protective effect after indomethacin administration, it can be reasonably assumed that there is no such protective effect. The use of a test dose of 100 mg i.m. indomethacin (INDOTEST) appears to provide a clear-cut answer in this situation. It may be a useful tool for a proper clinical assessment of unilateral headache with relatively short-lasting attacks when problems of classification arise. A correct diagnosis of CPH or CH is important, since a CPH diagnosis may imply a lifelong treatment with a potentially noxious drug.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing syndrome: a review

“…The highly variable frequency of attacks in SUNCT syndrome makes it difficult to determine whether an agent is truly potent. It has been suggested that controlled trials are not required in TACs because these conditions do not demonstrate a placebo effect [49,54]. This is not correct for cluster headache in which the reported placebo response rate is 7% to 62% [55].…”

Diagnostic and therapeutic errors in trigeminal autonomic cephalalgias and hemicrania continua: a systematic review

“…We are also aware, from clinical reports at congresses and from our personal observations, of instances in which other non-first-line medications, such as flunarizine or single, high-dose systemic steroid infusion for preventive treatment and indomethacin for acute treatment, were prescribed in CH patients. The above medications have been found to be ineffective in clinical trials [35,36]. Finally, up to 63% of CH sufferers used alternative therapies without finding any of them consistently effective [32].…”

“…In this regard, it is helpful to remember some differences between the two conditions such as frequency and duration of attacks (more frequent and shorter in PH than in CH), the sex dominance (male in CH and female in PH) and the patient behavior during the attacks (restless/agitated in CH and generally more quiet in PH). A positive response to indomethacin administration (the Indotest) is a sine qua non for the diagnosis of CPH [35]. A properly administered Indotest would prevent not only an incorrect diagnosis, but also the possibility to be prescribed with inappropriate treatment, pharmacological or surgical (multiple tooth extractions, stellate ganglion blocks, cervical sympathetic blocks, trigeminal sensory root section, infraorbital nerve section, sphenopalatine anesthetic injection and gangliectomy, infiltration of the point of Arnold, ethmoidosphenectomy) [25,38].…”

“…the mean ratio migraine/CEH for the presence of other symptoms were almost 5 for nausea, 4 for throbbing quality of pain, ca 3.5 for photophobia [42]). The response to the Indotest and/or to anesthetic blockade can definitively differentiate between these two similar conditions [35]. SH as a misdiagnosis of HC was reported not only by Rossi et al [15] but also in the Sinus, Allergy and Migraine Study [11].…”

Treatment of intractable hemicrania continua by occipital nerve stimulation

“…Patients were diagnosed in accordance with the International Classification of Headache Disorders criteria 3. All had unilateral headaches fully responsive to an oral or intramuscular Indotest,4 but had suffered intolerable side effects or had contraindications to long-term use of the drug. Patients had failed to respond to trials of at least five other medications with limited evidence of efficacy in HC: cyclo-oxygenase inhibitors, topiramate, verapamil, gabapentin, pregabalin, melatonin and flunarizine.…”