The interval between indomethacin administration and clinical response may be clinically relevant in the assessment of chronic paroxysmal hemicrania and hemicrania continua and other unilateral headache disorders with which they can be confounded. Eight patients with chronic paroxysmal hemicrania (6 women and 2 men) and 12 patients with hemicrania continua (8 women and 4 men) were entered into the study. The patients were given 50 mg of indomethacin intramuscularly (IM) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual attack pattern was reestablished prior to the second test.
The mean interval between attacks before the two injections (51 ± 18 minutes) in chronic paroxysmal hemicrania was significantly shorter than the mean after each of the two indomethacin injections (50 mg = 493 ± 251 minutes; 100 mg = 668 ± 211 minutes; P</i>0.001; Mann-Whitney test).
In every patient, there was a clear refractory period after indomethacin. Since the first “expected” attack after indomethacin administration did not occur, it can, with reasonable certainty, be assumed that the protective phase was initiated already prior to the time of the next “anticipated” attack. The mean attack duration was 22 minutes (last three attacks prior to test). The mean interval between the onset of two consecutive pretest attacks was 73 minutes. Since the interval between attacks was rather stable, one is, therefore, probably allowed to assume that the absolute protective effect of indomethacin on average had begun somewhere between 22 (mean attack duration) and 73 minutes after indomethacin injection.
Similarly, in hemicrania continua, the time between 50-mg indomethacin injection and complete pain relief was 73 ± 66 minutes. The pain-free period after indomethacin injection was around 13 hours (ie, 13 ± 8 hours after 50 mg and 13 ± 10 hours after 100 mg).
The use of a test dosage of 50 mg of indomethacin IM (‘indotest’) gives a clear-cut answer and may be a useful tool in the diagnostic arsenal in every unilateral headache for a proper clinical assessment. A diagnosis of chronic paroxysmal hemicrania or hemicrania continua is a serious matter because it may imply life-long treatment with a potentially noxious drug. It is, therefore, of the utmost importance that an ‘indotest’ is carried out in a standard fashion. In the future, the rules set forth in the present context should be followed, at least in scientific studies.
Pain pressure thresholds at cranial and extracranial levels were not significantly modified after indomethacin injection in any of the headaches.