Early Treatment of Migraine With Rizatriptan: A Placebo-Controlled Study

Houston Headache Clinic, Texas 77004, USA.
Headache The Journal of Head and Face Pain (Impact Factor: 2.71). 07/2004; 44(7):669-73. DOI: 10.1111/j.1526-4610.2004.04125.x
Source: PubMed


To evaluate the efficacy of rizatriptan when administered early during a migraine attack.
Several studies indicate that triptans are more efficacious when administered early during a migraine attack, when the pain is still mild.
One hundred and twelve rizatriptan-naïve patients aged 20 to 64 years with a history of migraine with or without aura that progressively worsened when left untreated were instructed to treat a total of three migraine attacks with either rizatriptan 10 mg or placebo as early as possible during each attack. Seventy-four patients (68 women and 6 men) were assigned to use the active drug and 38 (35 women and 3 men) to placebo. The primary efficacy endpoint was pain-free response at 2 hours after administration of the study drug. Secondary efficacy measures were pain-free response at 1 hour and sustained pain-free response lasting between 2 and 24 hours.
A total of 216 attacks were treated in the rizatriptan group and 109 in the placebo group. Pain-free response at 2 hours after early treatment was noted in 151 (70%) of attacks in the rizatriptan group and in 24 (22%) in the placebo group (P < .01). Pain-free response at 1 hour occurred in 97 (45%) and 9 (8%) attacks, respectively (P < .01). When the attacks were categorized by headache severity at the time of treatment, the pain-free response at 2 hours was higher for mild attacks than for moderate or severe attacks (P < .01). Sustained pain-free response after treatment was significantly higher for attacks treated with rizatriptan (60%) than for those treated with placebo (17%) (P < .001). Adverse events were observed in 62 patients in the rizatriptan group and 15 in the placebo group. Only 1 patient taking rizatriptan discontinued the study because of adverse events, and no serious adverse events were reported.
Rizatriptan is significantly more likely than placebo to produce a pain-free response within 2 hours when the drug is administered early in the migraine attack, when pain is mild rather than moderate or severe.

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    • "When compared with the therapeutic gain reported in two meta-analyses [10, 11] investigating rizatriptan efficacy in a general migraine population, our study yielded a 15 % absolute increase for 2 h pain freedom (46 vs. 31 %), 15 % for 2 h total migraine freedom (43 vs. 28 %),16 % for 2 h pain relief (49 vs. 33 %), 19 % for 2–24 h sustained pain freedom (37 vs. 18 %), 21 % for 2–24 h sustained pain relief (40 vs. 19 %), 28 % for eliminating nausea (49 vs. 21 %), 17 % for eliminating photophobia (45 vs. 28 %), and 7 % for eliminating phonophobia (33 vs. 26 %). Another interesting finding for clinical and research purposes was that in our patients, all of whom treated their migraine headache only when it became moderate to severe, the therapeutic gain for 2 h pain freedom and 2–24 h sustained pain free (46 and 37 %) almost matched that reported for early treatment (48 and 43 %) [12]. "
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    ABSTRACT: The objective and background is to confirm in a double-blind, placebo-controlled study the high triptan response rates we had previously reported in an open study in migraine patients with unilateral cranial autonomic symptoms. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 % [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %) (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. We confirm in a placebo-controlled study our previous data suggesting that the presence of unilateral cranial autonomic symptoms in migraineurs predicts a positive response to triptans, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.
    The Journal of Headache and Pain 03/2012; 13(5):407-14. DOI:10.1007/s10194-012-0440-y · 2.80 Impact Factor
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    • "Several of the acute trials investigate the relationship between the timing of drug intake (in relation to the onset of migraine pain or cutaneous allodynia) and drug efficacy [23, 62, 73, 86, 102, 103, 122, 130]. The results of these trials suggest that “early” triptan administration, while the headache is mild, is more efficient in terms of pain-free outcomes and reduced risk of recurrence when compared to “late” administration, when the headache is moderate to severe. "
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    ABSTRACT: In 2000, the Clinical Trials Subcommittee of the International Headache Society (IHS) published the second edition of its guidelines for controlled trials of drugs in migraine. The purpose of this publication was to improve the quality of such trials by increasing the awareness amongst investigators of the methodological issues specific to this particular illness. Until now the adherence to these guidelines has not been systematically assessed. We reviewed all published controlled trials of drugs in migraine from 2002 to 2008. Eligible trials were scored for compliance with the IHS guidelines by using grading scales based on the most essential recommendations of the guidelines. The primary efficacy measure of each trial was also recorded. A total of 145 trials of acute treatment and 52 trials of prophylactic treatment were eligible for review. Of the randomized, double-blind trials, acute trials scored an average of 4.7 out of 7 while prophylactic trials scored an average of 5.6 out of 9 for compliance. Thirty-one percent of acute trials and 72% of prophylactic trials used the recommended primary efficacy measure. Fourteen percent of the reviewed trials were either not randomized or not double-blinded. Adherence to international guidelines like these of IHS is important to ensure that only high-quality trials are performed, and to provide the consensus that is required for meta analyses. The primary efficacy measure for trials of acute treatment should be "pain free" and not "headache relief". Open-label or non-randomized trials generally have no place in the study of migraine drugs.
    The Journal of Headache and Pain 10/2010; 11(6):457-68. DOI:10.1007/s10194-010-0257-5 · 2.80 Impact Factor
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    • ". R = Rizatriptan: R1, Mathew et al. (2004) (37); R2, Cady et al. (2006) (31). F = frovatriptan: F1, Cady et al. (2004) (30). "
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    ABSTRACT: Gendolla A. Early treatment in migraine: how strong is the current evidence? Cephalalgia 2008; 28:28–35. London. ISSN 0333-1024 Over the last 10 years, triptans (serotonin 5-HT1B/1D receptor agonists) have proved to be efficacious in treating migraine pain. However, recent evidence suggests that patients are still not receiving optimal pain management, particularly in clinical trials, where triptan treatment is generally not initiated until pain has reached moderate intensity. Pathophysiological evidence indicates that if treatment is initiated at an early stage, while pain is still mild and before the onset of central sensitization, outcomes for patients may be improved. In addition, a small number of clinical trials have been reported in which triptans were taken early (within 1 h of pain onset) or while pain was still mild; although constraints of trial design and data analysis limit definite conclusions, overall the results suggest that this early/mild approach results in more rapid and sustained pain relief. New studies are therefore needed to clarify the clinical benefits of early treatment, whilst taking into account potential risks, such as medication overuse. Ultimately, migraine treatment strategies require optimization in order to meet patient expectations and to reduce the current burden of migraine-associated disability.
    Cephalalgia 10/2008; 28 Suppl 2(s2):28-35. DOI:10.1111/j.1468-2982.2008.01688.x · 4.89 Impact Factor
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