Prophylactic Treatment of Migraine With an Angiotensin II ReceptorBlocker

Abstract

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.

Preventive Pharmacologic Treatments for Episodic Migraine in Adults

“…89 Candesartan decreased migraine-related disability, but had no effect on use of drugs for acute migraine attacks. 90 In contrast, the ARB telmisartan was not better than placebo in reducing monthly migraine attacks by ≥50 %. 91 Comparative Effectiveness of Drugs for Prevention of Episodic Migraine.…”

“…84 Individual RCTs demonstrated that three off-label beta blockers-acebutolol 85 Table 8), improved headache index scores by ≥50 %, and reduced depression symptoms in adults with comorbid hypertension and depressive symptoms for whom previous preventive antimigraine drugs had been ineffective. 88 The ACE inhibitor lisinopril 89 (233 attributable events per 1,000 treated, 95 % CI, 124 to 343) and the ARB candesartan 90 (350 attributable events per 1,000 treated, 95 % CI, 219 to 481) were better than placebo in reducing monthly migraine attacks by ≥50 %. Lisinopril was better than placebo in reducing pain measured with the Short Form 36 (SF-36) questionnaire, but did not decrease use of drugs for acute migraine attacks.…”

“…Indirect adjusted frequentist analyses demonstrated no differences among approved drugs in reducing monthly headache frequency by ≥50 % (online Appendix Table 10). Indirect adjusted frequentist analyses offered low-strength evidence that off-label ARB candesartan 90 resulted in greater odds of clinical response than approved drugs (online Appendix Table 10). Exploratory network Bayesian meta-analyses demonstrated effectiveness of all approved drugs with no differences between them (Figure 2 and online Appendix Table 11).…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Moreover, the angiotensin AT 1 receptor antagonist candesartan (Tronvik et al 2003) also seems to be effective as prophylactic antimigraine drug, which may be generalized to other drugs from the same class as suggested by an open-label study in 24 patients using olmesartan (Charles et al 2006). In addition, genetic studies suggest an association between ACE gene polymorphisms and migraine (Paterna et al 2000).…”

Quality of Care Measures for Migraine: A Comprehensive Review

“…All of the non-patient-reported measures are classified as either diagnosis-related 42,44,45 (Table 2) or treatment-and preventionrelated 42,[44][45][46][47][48] (Tables 3 and 4). The RAND authors assert that screening for headaches is not recommended because the problem is symptomatic.…”