ContextThere is a paucity of effective, well-tolerated drugs available for migraine prophylaxis.Objective To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug.Design and Setting Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002.Patients Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements.Interventions A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan. Main Outcome MeasuresThe primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire. ResultsIn a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (P=.001) in the intention-to-treat analysis (n=57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95; PϽ.001), days with migraine (12.6 vs 9.0; PϽ.001), hours with migraine (92.2 vs 59.4; PϽ.001), headache severity index (293 vs 191; PϽ.001), level of disability (20.6 vs 14.1; PϽ.001) and days of sick leave (3.9 vs 1.4; P=.01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of Ն50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods. ConclusionIn this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.

The Nord-Trøndelag Health Study (HUNT 3) performed in 2006–2008 is a replication of the cross-sectional survey from 1995 to 1997 (HUNT 2). The aim of the present study was to assess the sensitivity and specificity of questionnaire-based headache diagnoses using a personal interview by a neurologist as a gold standard. For the questionnaire-based status as headache sufferer, a sensitivity of 88%, a specificity of 86%, and a kappa statistic of 0.70 were found. Chronic headache, chronic tension-type headache (TTH), and medication overuse headache (MOH) were diagnosed with a specificity of ≥99%, and a kappa statistic of ≥0.73. Lower figures were found for the diagnoses of migraine and TTH. For individuals with headache ≥1 day per month, a sensitivity of 58% (migraine) and 96% (TTH), a specificity of 91 and 69%, and a kappa statistic of 0.54 and 0.44 were found, respectively. The specificity for migraine with aura was 95%. In conclusion, the HUNT 3-questionnaire is a valid tool for identifying headache sufferers, and diagnosing patients with chronic headache, including chronic TTH and MOH. The more moderate sensitivity for migraine and TTH makes the questionnaire-based diagnoses of migraine and TTH suboptimal for determining the prevalence. However, the high specificity of the questionnaire-based diagnosis of migraine, in particular for migraine with aura, makes the questionnaire a valid tool for diagnosing patients with migraine for genetic studies.

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month x headache intensity x headache hours) at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had > or = 50% reduction in monthly headache days compared with 25% in the withdrawal group (P = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).

Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack.