A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine
Identifieur interne : 002386 ( Istex/Corpus ); précédent : 002385; suivant : 002387A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine
Auteurs : P. Tfelt-HansenSource :
- Cephalalgia [ 0333-1024 ] ; 2006.
Abstract
The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the ‘gold standard’ and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.
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DOI: 10.1111/j.1468-2982.2006.01194.x
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Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark.</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: tfelt@inet.uni2.dk</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B165AE08A0A963838CA3C6B15DC5BC82A49ED12F</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1111/j.1468-2982.2006.01194.x</idno><idno type="url">https://api-v5.istex.fr/document/B165AE08A0A963838CA3C6B15DC5BC82A49ED12F/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002386</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002386</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine</title><author wicri:is="90%"><name sortKey="Tfelt Hansen, P" sort="Tfelt Hansen, P" uniqKey="Tfelt Hansen P" first="P" last="Tfelt-Hansen">P. Tfelt-Hansen</name><affiliation><mods:affiliation>P. Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark.</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: tfelt@inet.uni2.dk</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Cephalalgia</title><idno type="ISSN">0333-1024</idno><idno type="eISSN">1468-2982</idno><imprint><publisher>SAGE Publications</publisher><pubPlace>Sage UK: London, England</pubPlace><date type="published" when="2006">2006</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1265">1265</biblScope><biblScope unit="page" to="1274">1274</biblScope></imprint><idno type="ISSN">0333-1024</idno></series><idno type="istex">B165AE08A0A963838CA3C6B15DC5BC82A49ED12F</idno><idno type="DOI">10.1111/j.1468-2982.2006.01194.x</idno><idno type="ArticleID">10.1111_j.1468-2982.2006.01194.x</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0333-1024</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the ‘gold standard’ and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.</div></front></TEI><istex><corpusName>sage</corpusName><author><json:item><name>P Tfelt-Hansen</name><affiliations><json:string>P. Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark.</json:string><json:string>E-mail: tfelt@inet.uni2.dk</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Migraine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>triptans</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>systematic review</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>meta-analysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>head-to-head comparison</value></json:item></subject><articleId><json:string>10.1111_j.1468-2982.2006.01194.x</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>review-article</json:string></originalGenre><abstract>The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. 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Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark.</affiliation></author></analytic><monogr><title level="j">Cephalalgia</title><idno type="pISSN">0333-1024</idno><idno type="eISSN">1468-2982</idno><imprint><publisher>SAGE Publications</publisher><pubPlace>Sage UK: London, England</pubPlace><date type="published" when="2006"></date><biblScope unit="volume">26</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1265">1265</biblScope><biblScope unit="page" to="1274">1274</biblScope></imprint></monogr><idno type="istex">B165AE08A0A963838CA3C6B15DC5BC82A49ED12F</idno><idno type="DOI">10.1111/j.1468-2982.2006.01194.x</idno><idno type="ArticleID">10.1111_j.1468-2982.2006.01194.x</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the ‘gold standard’ and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>Migraine</term></item><item><term>triptans</term></item><item><term>systematic review</term></item><item><term>meta-analysis</term></item><item><term>head-to-head comparison</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api-v5.istex.fr/document/B165AE08A0A963838CA3C6B15DC5BC82A49ED12F/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus sage not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="review-article" dtd-version="2.3" xml:lang="EN"><front><journal-meta><journal-id journal-id-type="publisher-id">CEP</journal-id><journal-id journal-id-type="hwp">spcep</journal-id><journal-title>Cephalalgia</journal-title><issn pub-type="ppub">0333-1024</issn><issn pub-type="epub">1468-2982</issn><publisher><publisher-name>SAGE Publications</publisher-name><publisher-loc>Sage UK: London, England</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1111/j.1468-2982.2006.01194.x</article-id><article-id pub-id-type="publisher-id">10.1111_j.1468-2982.2006.01194.x</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><xref ref-type="corresp" rid="corresp1-j.1468-2982.2006.01194.x"></xref></contrib><aff id="aff1-j.1468-2982.2006.01194.x">Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark</aff></contrib-group><author-notes><corresp id="corresp1-j.1468-2982.2006.01194.x">P. Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark. e-mail <email xlink:href="tfelt@inet.uni2.dk" xlink:type="simple">tfelt@inet.uni2.dk</email></corresp></author-notes><pub-date pub-type="epub-ppub"><month>11</month><year>2006</year></pub-date><volume>26</volume><issue>11</issue><fpage>1265</fpage><lpage>1274</lpage><history><date date-type="received"><day>23</day><month>10</month><year>2005</year></date><date date-type="accepted"><day>3</day><month>5</month><year>2006</year></date></history><permissions><copyright-statement>© 2006 International Headache Society</copyright-statement><copyright-year>2006</copyright-year><copyright-holder content-type="society">International Headache Society</copyright-holder></permissions><abstract><p>The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the ‘gold standard’ and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.</p></abstract><kwd-group><kwd>Migraine</kwd><kwd>triptans</kwd><kwd>systematic review</kwd><kwd>meta-analysis</kwd><kwd>head-to-head comparison</kwd></kwd-group></article-meta></front><body><sec id="section1-j.1468-2982.2006.01194.x" sec-type="intro"><title>Introduction</title><p>In 1996 Sackett et al. defined evidence-based medicine as follows: ‘Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research (<xref ref-type="bibr" rid="bibr1-j.1468-2982.2006.01194.x">1</xref>) … It is when asking questions about therapy that we should try to avoid the nonexperimental approaches, since they routinely lead to false positive conclusions about efficacy. Because the randomised trial, and especially the systematic review of several randomised trials, is so more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm’ (<xref ref-type="bibr" rid="bibr1-j.1468-2982.2006.01194.x">1</xref>).</p><p>Best clinical evidence is now available in migraine therapy and in the following a review by the American Consortium, six systematic reviews and five meta-analyses of drugs used for migraine therapy are presented and discussed.</p></sec><sec id="section2-j.1468-2982.2006.01194.x"><title>Review by the American Consortium</title><p>In 2000 the US Headache Consortium, consisting of seven member organizations with an interest in improving the quality of care for migraine patients, completed a landmark evidence-based review of the literature concerning the diagnosis and treatment of migraine (<xref ref-type="bibr" rid="bibr2-j.1468-2982.2006.01194.x">2</xref>–<xref ref-type="bibr" rid="bibr8-j.1468-2982.2006.01194.x">8</xref>). This was based on a literature search in English for controlled trials of treatments for migraine from 1966 to 1996, with additions of some newer randomized clinical trials (RCTs). The Consortium then reached agreement on a scale for quality of the evidence, as shown in <xref ref-type="table" rid="table1-j.1468-2982.2006.01194.x">Table 1</xref>.</p><table-wrap id="table1-j.1468-2982.2006.01194.x" position="float"><label>Table 1</label><caption><p>Ranking of acute and preventive drugs for migraine for scientific evidence in the American Guidelines (<xref ref-type="bibr" rid="bibr5-j.1468-2982.2006.01194.x">5</xref>, <xref ref-type="bibr" rid="bibr8-j.1468-2982.2006.01194.x">8</xref>)</p></caption><graphic alternate-form-of="table1-j.1468-2982.2006.01194.x" position="float" xlink:href="10.1111_j.1468-2982.2006.01194.x-table1.tif" xlink:type="simple"></graphic><table><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><tbody valign="top"><tr><td colspan="1" rowspan="1">A</td><td colspan="1" rowspan="1">Multiple well-designed randomized controlled trials, directly relevant to the recommendation, yielded a consistent pattern of finding</td></tr><tr><td colspan="1" rowspan="1">B</td><td colspan="1" rowspan="1">Some evidence from randomized clinical trials supported the recommendation, but the scientific support was not optimal. For instance, few randomized trials existed, the trials that exist were somewhat inconsistent, or the trials were not directly relevant to the recommendation. An example of the last point could be the case where a trial were conducted using a study group that differed from the target group for the recommendation</td></tr><tr><td colspan="1" rowspan="1">C</td><td colspan="1" rowspan="1">The US Headache Consortium achieved consensus on the recommendation in the absence of relevant randomized controlled trials</td></tr></tbody></table></table-wrap><p>In addition to this scale for quality of evidence, A to C, the drugs were graded on scales for scientific effect and for clinical impression of effect.</p><sec id="section3-j.1468-2982.2006.01194.x"><title>Acute migraine drugs</title><p>On the scale for quality of the evidence ergotamine received a grade B, dihydroergotamine nasal spray received a grade A, butalbital plus aspirin plus caffeine received a grade C, aspirin a grade A, acetaminophen plus aspirin plus caffeine a grade A, naproxen a grade A, ibuprofen a grade A, flurbiprofen a grade B, tolfenamic acid a grade A, paracetamol a grade B, isometheptene-containing compounds a grade B, corticosteroids a grade C, parenteral opiods a grade B, butorphanol nasal spray a grade A and triptans (sumatriptan nasal spray, sumatriptan subcutaneous injection, oral sumatriptan, naratriptan, zolmitriptan and rizatriptan) received a grade A (<xref ref-type="bibr" rid="bibr5-j.1468-2982.2006.01194.x">5</xref>).</p><p>This grading of acute treatment drugs for migraine is, however, to some extent controversial as discussed in the following.</p><p>Ergotamine received a grade B in accordance with a European Consensus (<xref ref-type="bibr" rid="bibr9-j.1468-2982.2006.01194.x">9</xref>) which recommended that, if used, ergotamine should be given by the rectal route. Aspirin received a grade A but should be graded in combination with metoclopramide and should in this combination receive a grade A (<xref ref-type="bibr" rid="bibr10-j.1468-2982.2006.01194.x">10</xref>). Paracetamol plus aspirin plus caffeine received a grade A. This rating is based on three randomized, placebo-controlled controlled trials published in one paper (<xref ref-type="bibr" rid="bibr11-j.1468-2982.2006.01194.x">11</xref>). It should be noted, however, that the most disabled segment of migraineurs, including those who usually required bed rest or who vomited 20% or more of the time, were excluded (<xref ref-type="bibr" rid="bibr11-j.1468-2982.2006.01194.x">11</xref>). The results can thus not be generalized to all migraine patients. Butorphanol nasal spray received a grade A based on two RCTs; but in one of the RCTs 57% of patients rated the drug as poor, probably due to frequent adverse events (AEs) (<xref ref-type="bibr" rid="bibr12-j.1468-2982.2006.01194.x">12</xref>). Buthorphanol should receive only grade B. The triptans, which have been investigated with up-to-date methodology (<xref ref-type="bibr" rid="bibr13-j.1468-2982.2006.01194.x">13</xref>, <xref ref-type="bibr" rid="bibr14-j.1468-2982.2006.01194.x">14</xref>), rightly received a grade A and they are currently the mainstay in the acute management of migraine (<xref ref-type="bibr" rid="bibr15-j.1468-2982.2006.01194.x">15</xref>).</p></sec><sec id="section4-j.1468-2982.2006.01194.x"><title>Prophylactic migraine drugs</title><p>Preventive drugs were similarly ranked A, B and C according to quality of evidence, but were also ranked according to clinical impression of effect and AEs:</p><list id="list1-j.1468-2982.2006.01194.x" list-type="simple"><list-item><p>Group 1. Medication with proven high efficacy and mild to moderate AEs.</p></list-item><list-item><p>Group 2. Medication with lower efficacy (i.e. limited number of studies, studies reporting conflicting results, efficacy suggesting only ‘modest’ improvement) and mild to moderate AEs.</p></list-item><list-item><p>Group 3. Medication use based on opinion, not randomized trials: (i) mild-to-moderate AEs; (ii) frequent or severe AEs (or safety concerns), complex management issue (special diets, high potential for severe adverse drug interactions, or drug holidays).</p></list-item><list-item><p>Group 4. Medication with proven efficacy but with frequent or severe AEs (or safety concerns), complex management issue (special diets, high potential for severe adverse drug interactions, or drug holidays).</p></list-item><list-item><p>Group 5. Medication proven to have little or no efficacy.</p></list-item></list><p>For preventive treatment of migraine the following ratings for quality of evidence and total ranking, in brackets, were given: clonidine received a grade B [5], carbamazepine a grade B [5], divalproex and valproate a grade A [1], gabapantin a grade B [2], vigabatrine a grade B [5], amitriptyline a grade A [1], nortriptyline a grade C [3a], fluoxetine a grade B [2], phenelzine a grade C [3b], atenolol a grade B [2], metoprolol a grade B [2], nadolol a grade B [2], propranolol a grade A [1], timolol a grade A [1], flunarizine a grade B [4], nimodipine a grade B [2], verapamil a grade B [2], ketoprofen a grade B [2], tolfenamic acid a grade B [2], naproxen a grade B [2], methysergide a grade A [4], pizotifen a grade A [4] and lisuride received a grade A [1] (<xref ref-type="bibr" rid="bibr8-j.1468-2982.2006.01194.x">8</xref>).</p><p>I have the following comments on these ratings. Clonidine rightly received a Grade B [5]. Three early double-blind, placebo-controlled RCTs apparently demonstrated the efficacy in migraine prophylaxis but later RCTs vs. placebo failed to confirms this (<xref ref-type="bibr" rid="bibr16-j.1468-2982.2006.01194.x">16</xref>). Clonidine is rarely used for migraine prophylaxis. Carbamazepin, grade B [5], has been found superior to placebo in only one RCT (<xref ref-type="bibr" rid="bibr17-j.1468-2982.2006.01194.x">17</xref>, <xref ref-type="bibr" rid="bibr18-j.1468-2982.2006.01194.x">18</xref>) and is seldom used in migraine prevention. Amitriptyline received a grade A [1] but AEs, dry mouth and sedation are frequent and often limit the clinical use of amitriptyline. There are four RCTs showing superiority of amitriptyline vs. placebo (<xref ref-type="bibr" rid="bibr16-j.1468-2982.2006.01194.x">16</xref>) and the drug should receive grade A [4]. Divalproex sodium and valproate received a grade A [1] based on four RCTs (<xref ref-type="bibr" rid="bibr18-j.1468-2982.2006.01194.x">18</xref>–<xref ref-type="bibr" rid="bibr22-j.1468-2982.2006.01194.x">22</xref>). They are second-line drugs for migraine prophylaxis but their use is hampered by AEs such as sedation, weight gain and tremor, and a grade A [2] would be more appropriate. Timolol, which was superior to placebo in three RCTs (<xref ref-type="bibr" rid="bibr23-j.1468-2982.2006.01194.x">23</xref>–<xref ref-type="bibr" rid="bibr26-j.1468-2982.2006.01194.x">26</xref>), was equivalent to propranolol in one RCT (<xref ref-type="bibr" rid="bibr25-j.1468-2982.2006.01194.x">25</xref>) and correctly received a grade A [1]. It is, however, not commonly used for migraine prophylaxis. Metoprolol received a grade B [2] but in my view the rating should be A [1]. Metoprolol was superior to placebo or aspirin in three RCTs using the recommended 200 mg of metoprolol (<xref ref-type="bibr" rid="bibr27-j.1468-2982.2006.01194.x">27</xref>–<xref ref-type="bibr" rid="bibr29-j.1468-2982.2006.01194.x">29</xref>) and somewhat better than placebo in one RCT using the dose of 100 mg metoprolol (<xref ref-type="bibr" rid="bibr26-j.1468-2982.2006.01194.x">26</xref>, <xref ref-type="bibr" rid="bibr30-j.1468-2982.2006.01194.x">30</xref>). In one comparative RCT metoprolol was comparable to propranolol (<xref ref-type="bibr" rid="bibr31-j.1468-2982.2006.01194.x">31</xref>), although with wide 95% confidence intervals (CIs) (<xref ref-type="bibr" rid="bibr32-j.1468-2982.2006.01194.x">32</xref>). Propranolol, grade A [1], was superior to placebo in 10 RCTs and comparable to placebo in two RCTs (<xref ref-type="bibr" rid="bibr26-j.1468-2982.2006.01194.x">26</xref>) and remains the standard first-line drug for migraine prophylaxis. Flunarizine, amazingly, received only a grade B [4], but should receive a grade A [2] because it was superior to placebo in six out of seven RCTs (<xref ref-type="bibr" rid="bibr33-j.1468-2982.2006.01194.x">33</xref>). Because of the side-effects of flunarizine it is a second-line agent for migraine prophylaxis. Nimodipine received a grade B [2] but two European RCTs have shown that it was not superior to placebo (<xref ref-type="bibr" rid="bibr33-j.1468-2982.2006.01194.x">33</xref>). As a consequence of these negative trials, nimodipine has not been registered for migraine prophylaxis in any country. It should be ranked B [5]. The evidence for verapamil (B [2]) is very sparse, 41 patients included in three RCTs (<xref ref-type="bibr" rid="bibr33-j.1468-2982.2006.01194.x">33</xref>). Pizotifen (A [4]) was superior to placebo in six RCTs and not superior to placebo in three RCTs (<xref ref-type="bibr" rid="bibr34-j.1468-2982.2006.01194.x">34</xref>). Again, AEs, especially weight gain and sedation, hamper its use and I agree with the A [4] rating. The anti-Parkinson agent lisuride received a grade A [1], but in two of the pivotal trials (<xref ref-type="bibr" rid="bibr35-j.1468-2982.2006.01194.x">35</xref>, <xref ref-type="bibr" rid="bibr36-j.1468-2982.2006.01194.x">36</xref>) migraine patients with up to 21–30 attacks per month were included. The diagnosis of migraine must therefore be questioned. Lisuride is not in general use for migraine prophylaxis and should receive B [2].</p></sec></sec><sec id="section5-j.1468-2982.2006.01194.x"><title>Systematic reviews in migraine</title><p>Within recent years several systematic reviews with meta-analyses of acute migraine treatment have been published (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>–<xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>). In addition, three systematic reviews of preventive migraine treatment have been published (<xref ref-type="bibr" rid="bibr47-j.1468-2982.2006.01194.x">47</xref>–<xref ref-type="bibr" rid="bibr49-j.1468-2982.2006.01194.x">49</xref>). One should distinguish between systematic reviews, where several RCTs of a single drug are evaluated by meta-analysis to gain a more precise impression of its merits (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>, <xref ref-type="bibr" rid="bibr42-j.1468-2982.2006.01194.x">42</xref>, <xref ref-type="bibr" rid="bibr43-j.1468-2982.2006.01194.x">43</xref>, <xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>–<xref ref-type="bibr" rid="bibr48-j.1468-2982.2006.01194.x">48</xref>), and systematic reviews, where several drugs or administration forms of a drug are compared in a meta-analysis (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>–<xref ref-type="bibr" rid="bibr41-j.1468-2982.2006.01194.x">41</xref>, <xref ref-type="bibr" rid="bibr44-j.1468-2982.2006.01194.x">44</xref>, <xref ref-type="bibr" rid="bibr45-j.1468-2982.2006.01194.x">45</xref>).</p><p>In the systematic reviews of acute migraine treatment (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>–<xref ref-type="bibr" rid="bibr43-j.1468-2982.2006.01194.x">43</xref>, <xref ref-type="bibr" rid="bibr45-j.1468-2982.2006.01194.x">45</xref>, <xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>) migraine was diagnosed according to the criteria of the International Headache Society (IHS) (<xref ref-type="bibr" rid="bibr50-j.1468-2982.2006.01194.x">50</xref>) and the same methodology was used (<xref ref-type="bibr" rid="bibr14-j.1468-2982.2006.01194.x">14</xref>). Patients treated moderate or severe headache and headache relief was defined as a decrease to none or mild (<xref ref-type="bibr" rid="bibr13-j.1468-2982.2006.01194.x">13</xref>). Headache relief was the primary efficacy measure in most RCTs. Pain-free after 2 h, which is now the recommended primary efficacy measure of the Subcommittee of IHS on Clinical Trials (<xref ref-type="bibr" rid="bibr14-j.1468-2982.2006.01194.x">14</xref>), was also reported in most studies and was evaluated in some meta-analyses (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>, <xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>). One of the systematic reviews (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>) also evaluated sustained pain free, i.e. pain free after 2 h, no use of rescue medication and no recurrence within 24 h, and consistency across attacks. In addition, tolerability vs. placebo was evaluated in these systematic reviews.</p></sec><sec id="section6-j.1468-2982.2006.01194.x"><title>Systematic reviews of drugs used for the acute treatment of migraine</title><p>Large amounts of data are needed to overcome random effects in estimating treatment effects (<xref ref-type="bibr" rid="bibr51-j.1468-2982.2006.01194.x">51</xref>). This is the background for systematic reviews of one drug for acute migraine treatment (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>, <xref ref-type="bibr" rid="bibr42-j.1468-2982.2006.01194.x">42</xref>, <xref ref-type="bibr" rid="bibr43-j.1468-2982.2006.01194.x">43</xref>, <xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>) or migraine prophylaxis (<xref ref-type="bibr" rid="bibr47-j.1468-2982.2006.01194.x">47</xref>–<xref ref-type="bibr" rid="bibr49-j.1468-2982.2006.01194.x">49</xref>). The systematic reviews, using meta-analysis, showed that naratriptan 2.5 mg was superior to placebo (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>); for a comment on the magnitude of the effect of naratriptan, see below. Rizatriptan 5 mg, the dose used in patients treated with propranolol for migraine prophylaxis, and rizatriptan 10 mg were superior to placebo (<xref ref-type="bibr" rid="bibr42-j.1468-2982.2006.01194.x">42</xref>). Rizatriptan 10 mg is a first-line drug for the treatment of migraine attacks. Eletriptan 40 mg and 80 mg were superior to placebo (<xref ref-type="bibr" rid="bibr43-j.1468-2982.2006.01194.x">43</xref>). Eletriptan 40 mg is a first-line drug for acute migraine attacks and eletriptan 80 mg can be tried in especially severe migraine attacks. In one systematic review the efficacy parameter pain-free response at 2 h was used (<xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>) and 100 mg sumatriptan was superior to placebo with numbers-needed-to-treat of 5.1. Sumatriptan 50 mg was not superior to placebo for this parameter (<xref ref-type="bibr" rid="bibr46-j.1468-2982.2006.01194.x">46</xref>). In a recent trial, 50 mg sumatriptan (50%) taken in the mild phase of a migraine attack was superior to placebo (29%) for pain free at 2 h (<xref ref-type="bibr" rid="bibr52-j.1468-2982.2006.01194.x">52</xref>).</p></sec><sec id="section7-j.1468-2982.2006.01194.x"><title>Meta-analysis of drugs used for the acute treatment of migraine</title><p>One systematic review of triptans presented a meta-analysis of the seven oral triptans (sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan and frovatriptan) and of subcutaneous, intranasal and rectal sumatriptan (<xref ref-type="bibr" rid="bibr45-j.1468-2982.2006.01194.x">45</xref>). The meta-analysis was based on headache relief and the mean therapeutic gains (TG) (percentage relief with active drug minus percentage relief with placebo) with 95% CIs were calculated. Based on this meta-analysis, subcutaneous sumatriptan 6 mg (TG = 51%; 95% CI 49, 53) and eletriptan 80 mg (TG = 42%; 95% CI 37, 47) were superior to sumatriptan 100 mg (TG = 32%; 95% CI 29, 34%). In contrast, the mean TGs were inferior to sumatriptan 100 mg for naratriptan 2.5 mg (TG = 22%; 95% CI 18, 26) and for frovatriptan (TG = 16%; 95% CI 8, 25).</p><p>In another systematic review (<xref ref-type="bibr" rid="bibr41-j.1468-2982.2006.01194.x">41</xref>), the meta-analysis was based on number-needed-to-treat (NNT) (the reciprocal of TG) and included oral triptans, subcutaneous sumatriptan, intranasal sumatriptan, intranasal dihydroergotamine and the oral combination of aspirin plus metoclopramide. Again, subcutaneous sumatriptan 6 mg (NNT = 2.0; 95% CI 1.8, 2.2) was superior to sumatriptan 100 mg (NNT = 3.3; 95% CI 3.0, 3.7) for headache relief, and the combination of aspirin plus metoclopramide (NNT = 3.2; 95% CI 2.6, 4.0) and intranasal dihyergotamine (NNT = 2.5; 95% CI 1.9, 3.7) were comparable to sumatriptan 100 mg. Rizatriptan 10 mg (NNT = 2.7: 95% CI 2.4, 2.9) was superior to sumatriptan; naratriptan 2.5 mg (NNT = 5.4; 95% CI 5.4, 9.2) was inferior to sumatriptan. For pain free after 2 h the combination of aspirin plus metoclopramide (NNT = 8.6; 95% CI 6.2, 14) was inferior to sumatriptan 100 mg (NNT = 4.7; 95% 95% CI 4.1, 5.5); and subcutaneous sumatriptan 6 mg (NNT = 2.1; 95% CI 1.9, 2.4) and rizatriptan 10 mg (NNT = 3.1; 95% CI 2.9, 3.5) were superior to sumatriptan 100 mg. In this meta-analysis excedrin (paracetamol 500 mg + aspirin 500 mg + caffeine 200 mg) had a NNT of 3.4 (95% CI 3.1, 3.8), but, as noted above, the patients with severely debilitating migraine were excluded from that study (<xref ref-type="bibr" rid="bibr11-j.1468-2982.2006.01194.x">11</xref>).</p><p>A third systematic review (<xref ref-type="bibr" rid="bibr40-j.1468-2982.2006.01194.x">40</xref>) reviewed the triptans available at that time in Canada: sumatriptan, rizatriptan, zolmitriptan and naratriptan. Subcutaneous 6 mg (NNT = 2.0; 95% CI 1.8, 2.3) was superior to oral sumatriptan 100 mg (NNT = 3.1; 95% CI 2.8, 3.4) for headache relief after 2 h. Naratriptan 2.5 mg (NNT = 5.1; 95% CI 4.1, 6.7) was inferior to oral sumatriptan 100 mg for this parameter. For pain free after 2 h rizatriptan 10 mg (NNT = 3.2; 95% CI 2.9, 3.5) was superior to sumatriptan 100 mg (NNT = 4.9; 95% CI 4.2, 5.9).</p><p>These three systematic reviews, in which therapeutic gains or NNT are used in the meta-analysis as a ‘correction’ for the variable placebo effect, generally give the same results. There are minor differences most likely due to differences in the RCTs included in the meta-analyses (<xref ref-type="bibr" rid="bibr40-j.1468-2982.2006.01194.x">40</xref>, <xref ref-type="bibr" rid="bibr41-j.1468-2982.2006.01194.x">41</xref>, <xref ref-type="bibr" rid="bibr45-j.1468-2982.2006.01194.x">45</xref>). From these systematic reviews one can conclude that subcutaneous sumatriptan 6 mg is the most effective triptan. Eletriptan 80 mg (for headache relief, pain free) and rizatriptan 10 mg (for pain free) are somewhat better than sumatriptan 100 mg, whereas naratriptan 2.5 mg and frovatriptan 2.5 mg are inferior to sumatriptan.</p><p>A meta-analysis of 53 RCTs with oral triptans was published in <italic>The Lancet</italic> (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>) and in detail in <italic>Cephalalgia</italic> (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). The following efficacy measures and tolerability were evaluated: headache relief after 2 h, pain free after 2 h, headache recurrence (headache relief after 2 h with a relapse of moderate or severe headache in the subsequent 22 h post dose), sustained pain free (pain free after 2 h, no recurrence of moderate or severe pain and no use of migraine medication over the subsequent 24 h post dose), intrapatient consistency for headache relief and pain free after 2 h, and AEs, both any AEs and CNS-related AEs. Some of the results of this meta-analysis are shown in <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a,b</xref>. The authors’ interpretation of the meta-analysis combined with evaluated comparator RCTs are shown in <xref ref-type="table" rid="table2-j.1468-2982.2006.01194.x">Table 2</xref> (for details see (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>)). Headache relief at 2 h was the primary per protocol end-point in nearly all triptan RCTs; and, as illustrated in <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a</xref>, headache relief after 2 h, compared with 100 mg sumatriptan, was higher for rizatriptan 10 mg and eletriptan 80 mg, lower for naratriptan 2.5 mg and frovatriptan 2.5 mg. For the placebo-substracted response, the same as TG (see above), only eletriptan 80 mg was superior to sumatriptan 100 mg. Pain free at 2 h, as recommended by the IHS (<xref ref-type="bibr" rid="bibr14-j.1468-2982.2006.01194.x">14</xref>), was a secondary end-point in most trials. Compared with sumatriptan 100 mg, naratriptan 2.5 mg showed lower absolute pain-free rates whereas eletriptan 80 mg, almotriptan 12.5 mg and rizatriptan 10 mg showed higher values; however, only eletriptan 80 mg and rizatriptan 10 mg showed higher values than sumatriptan for TG for pain free (placebo-substracted values) (see <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1b</xref>). Headache recurrence rates compared with sumatriptan 100 mg (30%; 95% CI 27, 33) were lower for eletriptan 40 mg (22%; 95% CI 19, 24) and 80 mg (20%; 95% CI 17, 22) and higher for rizatriptan 10 mg (37%; 95% CI 35, 39). Sustained pain free (for definition see above) was higher for rizatriptan 10 mg (26%; 95% CI 24, 27), eletriptan 80 mg (25%; 95% CI 23, 27) and almotriptan 12.5 mg (27%; 95% CI 23, 30) compared with sumatriptan 100 mg (20%; 95% CI 18, 21). Intrapatient consistency was evaluated in trials where the patients treated three attacks. Headache relief in two out of three attacks was found in 47–72% of patients (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). In one study (<xref ref-type="bibr" rid="bibr53-j.1468-2982.2006.01194.x">53</xref>) with crossover design, with placebo interspersed at random in four of five treatment groups (the fifth group received rizatriptan for four attacks), the consistency for rizatriptan was 86%. For AEs, sumatriptan 100 mg had a mean placebo-subtracted rate of any AEs of 13% (95% CI 8, 18). The rates for the other triptans overlap, except for lower values for almotriptan 12.5 mg and naratriptan 2.5 mg. The rates for almotriptan and naratriptan did not differ from placebo.</p><fig id="figure1-j.1468-2982.2006.01194.x" position="float"><label>Figure 1</label><caption><p>Headache response (a) and pain free after 2 h (b) after seven oral triptans. The shaded area indicates the 95% confidence intervals for sumatriptan 100 mg both for absolute responses and placebo-substracted results (from (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>) with permission from the publisher).</p></caption><graphic position="float" xlink:href="10.1111_j.1468-2982.2006.01194.x-fig1.tif" xlink:type="simple"></graphic></fig><table-wrap id="table2-j.1468-2982.2006.01194.x" position="float"><label>Table 2</label><caption><p>Comparison of the main efficacy and tolerability measures for oral triptans vs. sumatriptan based on the results of the meta-analysis and direct comparative trials, from Ferrari et al. (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>)</p></caption><graphic alternate-form-of="table2-j.1468-2982.2006.01194.x" position="float" xlink:href="10.1111_j.1468-2982.2006.01194.x-table2.tif" xlink:type="simple"></graphic><table><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead valign="bottom"><tr><td colspan="1" rowspan="1"></td><td colspan="1" rowspan="1">Initial 2-h relief</td><td colspan="1" rowspan="1">Sustained pain free</td><td colspan="1" rowspan="1">Consistency</td><td colspan="1" rowspan="1">Tolerability</td></tr></thead><tbody valign="top"><tr><td colspan="1" rowspan="1">Sumatriptan 50 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=/–</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Sumatriptan 25 mg</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">=/–</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">+</td></tr><tr><td colspan="1" rowspan="1">Zolmitriptan 2.5 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Zolmitriptan 5 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Naratriptan 2.5 mg</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">+ +</td></tr><tr><td colspan="1" rowspan="1">Rizatriptan 5 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Rizatriptan 10 mg</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+ +</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Eletriptan 20 mg</td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1"></td><td colspan="1" rowspan="1">–</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Eletriptan 40 mg</td><td colspan="1" rowspan="1">=/+</td><td colspan="1" rowspan="1">=/+</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Eletriptan 80 mg</td><td colspan="1" rowspan="1">+(+)</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">–</td></tr><tr><td colspan="1" rowspan="1">Almotriptan 12.5 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+ +</td></tr></tbody></table><table-wrap-foot><fn id="table-fn1-j.1468-2982.2006.01194.x"><p>=, No difference when compared with 100 mg sumatriptan; +, better when compared with sumatriptan; –, inferior when compared with sumatriptan.</p></fn></table-wrap-foot></table-wrap><p>The authors concluded that at marketed doses, all oral triptans were effective and well tolerated. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>).</p><p>I agree that all triptans are more effective than placebo but the therapeutic gains for both naratriptan and frovatriptan are low (<xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a</xref>), and lower than the therapeutic gain for the combination of aspirin plus metoclopramide (<xref ref-type="bibr" rid="bibr41-j.1468-2982.2006.01194.x">41</xref>). These two triptans are also more costly than the combination.</p><p>Rizatriptan 10 mg is rated with + for initial 2-h relief compared with sumatriptan 100 mg (see <xref ref-type="table" rid="table2-j.1468-2982.2006.01194.x">Table 2</xref>). The TG for rizatriptan 10 mg was, however, not superior to sumatriptan (<xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a</xref>) and, in a rather large comparator RCT, the two drugs were comparable for this efficacy measure (<xref ref-type="bibr" rid="bibr54-j.1468-2982.2006.01194.x">54</xref>). For pain free after 2 h, however, the TG was higher for rizatriptan 10 mg than for sumatriptan 100 mg, and the same was found in the comparative RCT (<xref ref-type="bibr" rid="bibr54-j.1468-2982.2006.01194.x">54</xref>). In addition, rizatriptan 10 mg (<italic>n</italic> = 1114) was superior (95% CI 0.6, 9) to sumatriptan 50 mg (<italic>n</italic> = 1116) for pain free after 2 h in a combined analysis of two trials (<xref ref-type="bibr" rid="bibr55-j.1468-2982.2006.01194.x">55</xref>, <xref ref-type="bibr" rid="bibr56-j.1468-2982.2006.01194.x">56</xref>). Rizatriptan 10 mg was superior to sumatriptan 100 mg for sustained pain free (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>), but this was not the case in the comparative RCT (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). Consistency was higher for rizatriptan 10 mg than for all other triptans, but it should be noted that this was evaluated with a special design (<xref ref-type="bibr" rid="bibr53-j.1468-2982.2006.01194.x">53</xref>) and the results are thus not directly comparable.</p><p>After the publication of this systematic review (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>) a new, large, placebo-controlled RCT comparing eletriptan 40 mg and sumatriptan was published (<xref ref-type="bibr" rid="bibr57-j.1468-2982.2006.01194.x">57</xref>). This study, together with two previous RCTs (<xref ref-type="bibr" rid="bibr58-j.1468-2982.2006.01194.x">58</xref>, <xref ref-type="bibr" rid="bibr59-j.1468-2982.2006.01194.x">59</xref>), constitutes a large head-to-head comparator database. A review of data from these three double-blind, placebo-controlled trials included 1132 patients treated with 40 mg eletriptan and 1129 patients treated with 100 mg sumatriptan (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>). In these comparative RCTs sumatriptan was encapsulated and it has been questioned whether encapsulation could influence the results against sumatriptan in these comparative RCTs (<xref ref-type="bibr" rid="bibr61-j.1468-2982.2006.01194.x">61</xref>). The mean TG for headache relief for 100 mg sumatriptan in these three trials (<xref ref-type="bibr" rid="bibr57-j.1468-2982.2006.01194.x">57</xref>, <xref ref-type="bibr" rid="bibr58-j.1468-2982.2006.01194.x">58</xref>, <xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>) was 31.2% (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>), which is equivalent to results of meta-analysis for 100 mg sumatriptan (32%; 95% CI 29, 34 (<xref ref-type="bibr" rid="bibr44-j.1468-2982.2006.01194.x">44</xref>); 29%; 95% CI 26, 34 (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>)). For pain free after 2 h the mean TG for 100 mg sumatriptan was 20% (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>), which is comparable to results from the meta-analysis: 19% (95% CI 17, 22) (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). The sustained pain free for sumatriptan was marginally lower (mean = 15%; 95% CI 13, 17) (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>) than the results from meta-analysis (mean = 20%; 95% CI 18, 21) (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). It should be noted that there is no placebo correction for sustained pain free, which makes comparison difficult. In conclusion, encapsulated 100 mg sumatriptan resulted in similar efficacy at 2 h to sumatriptan used in other placebo-controlled RCTs. The headache relief rate after 2 h was higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (57%) (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>). The 2-h pain-free response was also higher for eletriptan (35%) than for sumatriptan (25%) (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>). The sustained pain-free response was higher for eletriptan (22%) than for sumatriptan (15%) (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>). The frequency of AEs was similar for the two drugs (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>). Eletriptan 40 mg is thus superior to sumatriptan 100 mg for several efficacy measures in comparator RCTs. Eletriptan 80 mg, a dose not routinely used, was in the meta-analysis superior to sumatriptan 100 mg for TGs for headache relief, pain free after 2 h (see <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a,b</xref>) and sustained pain free (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>) This was also the case in the comparator studies (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>).</p><p>Almotriptan 12.5 mg had the same initial 2-h relief as sumatriptan 100 mg (see <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a,b</xref>). The headache relief was the same and the TG for pain free after 2 h was the same for almotriptan and sumatriptan. In one comparative RCT (<xref ref-type="bibr" rid="bibr62-j.1468-2982.2006.01194.x">62</xref>), however, almotriptan 12.5 mg (18%) was inferior to sumatriptan 50 mg (25%) for pain free after 2 h. Apparently, almotriptan 12.5 mg is better than sumatriptan 100 mg for sustained pain free, based on the meta-analysis (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). This was, however, not the case in a comparative RCT (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>) and in a larger crossover RCT (<xref ref-type="bibr" rid="bibr62-j.1468-2982.2006.01194.x">62</xref>), published after the meta-analysis, almotriptan 12.5 mg had a lower sustained pain-free response (12.9%) than sumatriptan 50 mg (17.6%) (<xref ref-type="bibr" rid="bibr63-j.1468-2982.2006.01194.x">63</xref>). Part of the explanation for the high sustained pain-free response for almotriptan in the meta-analysis may be the relatively high placebo response for this measure in the almotriptan RCTs (<xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>). Sustained pain free, as used in the meta-analysis, is not corrected for the placebo response. The better tolerability of almotriptan 12.5 mg than sumatriptan was confirmed in two trials (<xref ref-type="bibr" rid="bibr62-j.1468-2982.2006.01194.x">62</xref>, <xref ref-type="bibr" rid="bibr64-j.1468-2982.2006.01194.x">64</xref>). In one comparative RCT treatment-related AEs occurred more frequently with 50 mg sumatriptan (15.5%) than with 12.5 mg almotriptan (9.1%) (<xref ref-type="bibr" rid="bibr62-j.1468-2982.2006.01194.x">62</xref>); and in another comparative RCT the incidence of AEs was higher with 100 mg sumatriptan (22.2%) than with 12.5 mg almotriptan (8.7%) and the incidence of AEs was the same for 12.5 mg almotriptan as for placebo (6.1%) (<xref ref-type="bibr" rid="bibr64-j.1468-2982.2006.01194.x">64</xref>).</p><p>Intrapatient consistency as evaluated in the meta-analysis was investigated in only a few RCTs (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>) and is difficult to judge because this measure is not placebo-corrected, even though placebo values are presented. The placebo response for this measure is higher for almotriptan 12.5 mg than for sumatriptan 100 mg (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>) and if this is taken into account the consistency is most likely the same for almotriptan and sumatriptan, both for headache relief and pain free after 2 h.</p><p>My suggestions for the ratings of rizatriptan 10 mg, eletriptan 40 mg and 80 mg, and almotriptan 12.5 mg vs. sumatriptan 100 mg are shown in <xref ref-type="table" rid="table3-j.1468-2982.2006.01194.x">Table 3</xref>, which should be compared with <xref ref-type="table" rid="table2-j.1468-2982.2006.01194.x">Table 2</xref>. Rizatriptan 10 mg should have a +/= rating for initial 2-h relief and for sustained pain free, whereas the rest of the rating is unchanged. Eletriptan 40 mg should have + for initial relief based on the three comparator RCTs (<xref ref-type="bibr" rid="bibr60-j.1468-2982.2006.01194.x">60</xref>) and the same is the case for sustained pain free. Eletriptan 80 mg is unchanged. Almotriptan 12.5 mg is in my view comparable to sumatriptan 100 mg for initial relief, sustained pain free and consistency, but its better tolerability, comparable to placebo, has been confirmed in two RCTs (<xref ref-type="bibr" rid="bibr62-j.1468-2982.2006.01194.x">62</xref>, <xref ref-type="bibr" rid="bibr63-j.1468-2982.2006.01194.x">63</xref>).</p><table-wrap id="table3-j.1468-2982.2006.01194.x" position="float"><label>Table 3</label><caption><p>My personal comparison of the main efficacy and tolerability measures for selected triptans vs. 100 mg sumatriptan based on the results of the meta-analysis (<xref ref-type="bibr" rid="bibr37-j.1468-2982.2006.01194.x">37</xref>), direct comparator trials (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>) and later published results (<xref ref-type="bibr" rid="bibr56-j.1468-2982.2006.01194.x">56</xref>, <xref ref-type="bibr" rid="bibr61-j.1468-2982.2006.01194.x">61</xref>, <xref ref-type="bibr" rid="bibr65-j.1468-2982.2006.01194.x">65</xref>)—modified from (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>)</p></caption><graphic alternate-form-of="table3-j.1468-2982.2006.01194.x" position="float" xlink:href="10.1111_j.1468-2982.2006.01194.x-table3.tif" xlink:type="simple"></graphic><table><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead valign="bottom"><tr><td colspan="1" rowspan="1"></td><td colspan="1" rowspan="1">Initial 2 h relief</td><td colspan="1" rowspan="1">Sustained pain free</td><td colspan="1" rowspan="1">Consistency</td><td colspan="1" rowspan="1">Tolerability</td></tr></thead><tbody valign="top"><tr><td colspan="1" rowspan="1">Rizatriptan 10 mg</td><td colspan="1" rowspan="1">=/+</td><td colspan="1" rowspan="1">+/=</td><td colspan="1" rowspan="1">+ +<xref ref-type="table-fn" rid="table-fn3-j.1468-2982.2006.01194.x">∗</xref></td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Eletriptan 40 mg</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+/=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td></tr><tr><td colspan="1" rowspan="1">Eletriptan 80 mg</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">+</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">–</td></tr><tr><td colspan="1" rowspan="1">Almotriptan 12.5 mg</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">=</td><td colspan="1" rowspan="1">+ +</td></tr></tbody></table><table-wrap-foot><fn id="table-fn2-j.1468-2982.2006.01194.x"><p>=, No difference when compared with 100 mg sumatriptan; +, better when compared with sumatriptan; –, inferior when compared with sumatriptan.</p></fn><fn id="table-fn3-j.1468-2982.2006.01194.x"><label>∗</label><p>Consistency for rizatriptan 10 mg was investigated with a different methodology than normally used in the meta-analysis, see text.</p></fn></table-wrap-foot></table-wrap><p>In two recently published RCTs (<xref ref-type="bibr" rid="bibr65-j.1468-2982.2006.01194.x">65</xref>) with sumatriptan rapid-release tablets, sumatriptan 100 mg (<italic>n</italic> = 1101) had a TG of 30% (95% CI 26, 34) vs. placebo (<italic>n</italic> = 1113), the same as in the meta-nalysis (<xref ref-type="bibr" rid="bibr38-j.1468-2982.2006.01194.x">38</xref>, <xref ref-type="bibr" rid="bibr39-j.1468-2982.2006.01194.x">39</xref>) (see <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a</xref>). In contrast, for pain free after 2 h the mean TG was 32% (95% CI 28, 36) (<xref ref-type="bibr" rid="bibr65-j.1468-2982.2006.01194.x">65</xref>), which is considerable higher than the 20% TG for conventional sumatriptan tablets (see <xref ref-type="fig" rid="figure1-j.1468-2982.2006.01194.x">Fig. 1a</xref>). Unfortunately, there are no comparative RCTs with this new oral formulation of sumatriptan, and one can thus not draw firm conclusions concerning its merits relative to other triptans.</p></sec><sec id="section8-j.1468-2982.2006.01194.x"><title>Systematic reviews of drugs for migraine prophylaxis</title><p>In one systematic review of propranolol (<xref ref-type="bibr" rid="bibr47-j.1468-2982.2006.01194.x">47</xref>) it was concluded that propranolol is effective for short-term migraine prophylaxis, evidence on long-term effects is lacking, and propranonol seems to be as effective and safe as a variety of other drugs used for migraine prophylaxis. Propranolol is a first-line drug for migraine prophylaxis. In another systematic review the efficacy of feverfew in migraine prophylaxis was judged as unproven (<xref ref-type="bibr" rid="bibr48-j.1468-2982.2006.01194.x">48</xref>).</p><p>In one systematic review, a group of drugs, anticonvulsants, was evaluated for migraine prophylaxis (<xref ref-type="bibr" rid="bibr49-j.1468-2982.2006.01194.x">49</xref>). It was concluded that relatively few robust trials are available for agents other than sodium valproate/divalproex sodium, which is superior to placebo. Topiramate was effective in two RCTs and further RCTs were awaited (<xref ref-type="bibr" rid="bibr49-j.1468-2982.2006.01194.x">49</xref>). Valproate/divalproex sodium are second-line, not first-line drugs for migraine prophylaxis because of their AEs. Topiramate has been evaluated in three large RCTs and was superior to placebo in all three (<xref ref-type="bibr" rid="bibr66-j.1468-2982.2006.01194.x">66</xref>–<xref ref-type="bibr" rid="bibr68-j.1468-2982.2006.01194.x">68</xref>). It was comparable to propranolol (<xref ref-type="bibr" rid="bibr67-j.1468-2982.2006.01194.x">67</xref>). There are AEs, sedation and cognitive impairment, with topiramate and its place in migraine prophylaxis depends on how patients in clinical practice will tolerate the drug.</p></sec><sec id="section9-j.1468-2982.2006.01194.x" sec-type="conclusions"><title>Conclusions</title><p>When comparing drugs for the acute treatment of migraine, head-to-head comparative RCTs remain the ‘gold standard’. However, comparative trials are, with a few exceptions (<xref ref-type="bibr" rid="bibr53-j.1468-2982.2006.01194.x">53</xref>, <xref ref-type="bibr" rid="bibr54-j.1468-2982.2006.01194.x">54</xref>, <xref ref-type="bibr" rid="bibr56-j.1468-2982.2006.01194.x">56</xref>, <xref ref-type="bibr" rid="bibr57-j.1468-2982.2006.01194.x">57</xref>), relatively small and may overlook differences. In addition, there may be a selection bias in head-to-head RCTs: a patient responding well to the standard drug may be less likely to participate. Not all drugs in a class of drugs will be compared in head-to-head RCTs. Meta-analysis of drugs that underwent placebo-controlled RCTs with similar methodology (<xref ref-type="bibr" rid="bibr13-j.1468-2982.2006.01194.x">13</xref>, <xref ref-type="bibr" rid="bibr14-j.1468-2982.2006.01194.x">14</xref>) can therefore be a useful supplement when drugs are compared. The main weakness of the meta-analytic approach is that there is no randomization. In addition, the populations may not be totally comparable: possible bias in time with recruiting over many years and severity of headache (ratio of moderate/severe headaches) (<xref ref-type="bibr" rid="bibr69-j.1468-2982.2006.01194.x">69</xref>) may differ in different trials and trial programmes. The main emphasis when judging meta-analytic results should therefore be on therapeutic gains; and these results should be evaluated in context with the findings from head-to-head comparative trials.</p></sec></body><back><ref-list><title>References</title><ref id="bibr1-j.1468-2982.2006.01194.x"><label>1</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Sackett</surname><given-names>DL</given-names></name><name name-style="western"><surname>Rosenberg</surname><given-names>WM</given-names></name><name name-style="western"><surname>Gray</surname><given-names>JA</given-names></name><name name-style="western"><surname>Haynes</surname><given-names>RB</given-names></name><name name-style="western"><surname>Richardson</surname><given-names>WS.</given-names></name></person-group><article-title>Evidence based medicine: what it is and it isn’t</article-title>. <source>BMJ</source><year>1996</year>; <volume>312</volume>:<fpage>71</fpage>–<lpage>2</lpage>.</citation></ref><ref id="bibr2-j.1468-2982.2006.01194.x"><label>2</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Matchar</surname><given-names>DB</given-names></name><name name-style="western"><surname>McCrory</surname><given-names>DC</given-names></name><name name-style="western"><surname>Gray</surname><given-names>RN.</given-names></name></person-group><article-title>Toward evidence-based management of migraine</article-title>. <source>JAMA</source><year>2000</year>; <volume>284</volume>:<fpage>2640</fpage>–<lpage>1</lpage>.</citation></ref><ref id="bibr3-j.1468-2982.2006.01194.x"><label>3</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name></person-group>, <collab xlink:type="simple">Rosenberg.</collab><article-title>Multispeciality consensus on diagnosis and treatment of migaine</article-title>. <source>Neurology</source><year>2000</year>; <volume>54</volume>:<fpage>1253</fpage>.</citation></ref><ref id="bibr4-j.1468-2982.2006.01194.x"><label>4</label><citation citation-type="other" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>McCrory</surname><given-names>DC</given-names></name><name name-style="western"><surname>Matchar</surname><given-names>DB</given-names></name><name name-style="western"><surname>Gray</surname><given-names>RN</given-names></name><name name-style="western"><surname>Rosenberg</surname><given-names>JH</given-names></name><name name-style="western"><surname>Silberstein</surname><given-names>SD.</given-names></name></person-group><article-title>Evidence-Based Guidelines for Migraine Headache. Overview of Program Description and Methology.</article-title><comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.aan.com/professionals/practice/pdfs/gl0086.pdf" xlink:type="simple">http://www.aan.com/professionals/practice/pdfs/gl0086.pdf</ext-link> Last assessed</comment><year>29 July 2004</year>.</citation></ref><ref id="bibr5-j.1468-2982.2006.01194.x"><label>5</label><citation citation-type="other" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Matchar</surname><given-names>DB</given-names></name><name name-style="western"><surname>Young</surname><given-names>WB</given-names></name><name name-style="western"><surname>Rosenberg</surname><given-names>JH</given-names></name><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name><name name-style="western"><surname>Lipton</surname><given-names>RB</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name></person-group>. <article-title>Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management of Acute Attacks.</article-title><comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.aan.com/professionals/practice/pdfs/gl0087.pdf" xlink:type="simple">http://www.aan.com/professionals/practice/pdfs/gl0087.pdf</ext-link> Last assessed</comment><year>29 July 2004</year>. <comment>A summary can be found at: <ext-link ext-link-type="uri" xlink:href="http://www.neurology.org.cgi/reprint/55/6/754.pdf" xlink:type="simple">http://www.neurology.org.cgi/reprint/55/6/754.pdf</ext-link> Last assessed 4 September 2005.</comment></citation></ref><ref id="bibr6-j.1468-2982.2006.01194.x"><label>6</label><citation citation-type="other" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Frisberg</surname><given-names>BM</given-names></name><name name-style="western"><surname>Roseberg</surname><given-names>JH</given-names></name><name name-style="western"><surname>Matchar</surname><given-names>DB</given-names></name><name name-style="western"><surname>McCrory</surname><given-names>DC</given-names></name><name name-style="western"><surname>Pietrzak</surname><given-names>MP</given-names></name><name name-style="western"><surname>Rozen</surname><given-names>TD</given-names></name><etal></etal></person-group><article-title>Evidence-Based Guidelines for Migraine Headaches: Neuroimaging in Patients with Nonacute Headaches.</article-title><comment>Available at <ext-link ext-link-type="uri" xlink:href="http://www.aan.com/professionals/practice/pdfs/gl0088.pdf" xlink:type="simple">http://www.aan.com/professionals/practice/pdfs/gl0088.pdf</ext-link> Last assessed</comment><year>29 July 2004</year>.</citation></ref><ref id="bibr7-j.1468-2982.2006.01194.x"><label>7</label><citation citation-type="other" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Campbell</surname><given-names>JK</given-names></name><name name-style="western"><surname>Penzien</surname><given-names>DB</given-names></name><name name-style="western"><surname>Wall</surname><given-names>EM.</given-names></name></person-group><article-title>Evidence-Based Guidelines for Migraine Headache: Behaveriol and Physical Treatment.</article-title><comment>Available at <ext-link ext-link-type="uri" xlink:href="http://www.aan.com/professionals/practice/pdfs/gl0088.pdf" xlink:type="simple">http://www.aan.com/professionals/practice/pdfs/gl0088.pdf</ext-link> Last assessed</comment><year>29 July 2004</year>.</citation></ref><ref id="bibr8-j.1468-2982.2006.01194.x"><label>8</label><citation citation-type="other" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name><name name-style="western"><surname>Freitag</surname><given-names>FG</given-names></name><name name-style="western"><surname>Gilbert</surname><given-names>TT</given-names></name><name name-style="western"><surname>Frishberg</surname><given-names>BM.</given-names></name></person-group><article-title>Evidence-Based Guidelines for Migraine Headache in the Primary Care. Pharmacological Management for Prevention of Migraine.</article-title><comment>Available at <ext-link ext-link-type="uri" xlink:href="http://www.aan.com/professionals/practice/pdfs/gl0090.pdf" xlink:type="simple">http://www.aan.com/professionals/practice/pdfs/gl0090.pdf</ext-link> Last assessed</comment><year>29 July 2004</year>. <comment>A summary can be found at: <ext-link ext-link-type="uri" xlink:href="http://www.neurology.org.cgi/reprint/55/6/754.pdf" xlink:type="simple">http://www.neurology.org.cgi/reprint/55/6/754.pdf</ext-link> Last assessed 4 September 2005.</comment></citation></ref><ref id="bibr9-j.1468-2982.2006.01194.x"><label>9</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Saxena</surname><given-names>PR</given-names></name><name name-style="western"><surname>Dahlof</surname><given-names>C</given-names></name><name name-style="western"><surname>Pascual</surname><given-names>J</given-names></name><name name-style="western"><surname>Lainez</surname><given-names>M</given-names></name><name name-style="western"><surname>Henry</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Ergotamine in the acute treatment of migraine—European Consensus</article-title>. <source>Brain</source><year>2000</year>; <volume>123</volume>:<fpage>9</fpage>–<lpage>18</lpage>.</citation></ref><ref id="bibr10-j.1468-2982.2006.01194.x"><label>10</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Rolan</surname><given-names>P.</given-names></name></person-group><article-title>Nonsteroidal antiinflammatory drugs in the acute treatment of migraine</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>449</fpage>–<lpage>57</lpage>.</citation></ref><ref id="bibr11-j.1468-2982.2006.01194.x"><label>11</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Lipton</surname><given-names>RB</given-names></name><name name-style="western"><surname>Stewart</surname><given-names>WF</given-names></name><name name-style="western"><surname>Ryan</surname><given-names>RE</given-names><suffix>Jr</suffix></name><name name-style="western"><surname>Saper</surname><given-names>J</given-names></name><name name-style="western"><surname>Silbestein</surname><given-names>S</given-names></name><name name-style="western"><surname>Sheftell</surname><given-names>F.</given-names></name></person-group><article-title>Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials</article-title>. <source>Arch Neurol</source><year>1998</year>; <volume>55</volume>:<fpage>210</fpage>–<lpage>7</lpage>.</citation></ref><ref id="bibr12-j.1468-2982.2006.01194.x"><label>12</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Young</surname><given-names>WB</given-names></name><name name-style="western"><surname>Silberstein</surname><given-names>SD.</given-names></name></person-group><article-title>Antiemetics, prokinetics, neuroleptic and miscellaneous drugs in the acute treatment of migraine</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>505</fpage>–<lpage>13</lpage>.</citation></ref><ref id="bibr13-j.1468-2982.2006.01194.x"><label>13</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Pilgrim</surname><given-names>AJ.</given-names></name></person-group><article-title>Methodology of clinical trials of sumatriptan in migraine and cluster headache</article-title>. <source>Eur Neurol</source><year>1991</year>; <volume>31</volume>:<fpage>295</fpage>–<lpage>9</lpage>.</citation></ref><ref id="bibr14-j.1468-2982.2006.01194.x"><label>14</label><citation citation-type="journal" xlink:type="simple"><collab xlink:type="simple">International Headache Society Clinical Trial Subcommittee.</collab><article-title>Guidelines for Controlled Trials of Drugs in Migraine. Second edition</article-title>. <source>Cephalalgia</source><year>2000</year>; <volume>20</volume>:<fpage>765</fpage>–<lpage>86</lpage>.</citation></ref><ref id="bibr15-j.1468-2982.2006.01194.x"><label>15</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Saxena</surname><given-names>PR</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P.</given-names></name></person-group><article-title>Triptans, 5HT1B/1D agonists in the acute treatment of migraine</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>469</fpage>–<lpage>503</lpage>.</citation></ref><ref id="bibr16-j.1468-2982.2006.01194.x"><label>16</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Evers</surname><given-names>S</given-names></name><name name-style="western"><surname>Mylecharane</surname><given-names>EJ.</given-names></name></person-group><article-title>Nonsteroidal anti-inflammatory and miscellaneous drugs in migraine prophylaxis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>553</fpage>–<lpage>66</lpage>.</citation></ref><ref id="bibr17-j.1468-2982.2006.01194.x"><label>17</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Rompel</surname><given-names>H</given-names></name><name name-style="western"><surname>Bauermeister</surname><given-names>PW.</given-names></name></person-group><article-title>Aetiology of migraine and prevention with carbamazepine (Tegretol): results of a double-blind crossover study</article-title>. <source>A Afr Med J</source><year>1970</year>; <volume>44</volume>:<fpage>75</fpage>–<lpage>80</lpage>.</citation></ref><ref id="bibr18-j.1468-2982.2006.01194.x"><label>18</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P.</given-names></name></person-group><article-title>Antiepileptic drugs in migrine prophylaxis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edition</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>545</fpage>–<lpage>51</lpage>.</citation></ref><ref id="bibr19-j.1468-2982.2006.01194.x"><label>19</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Jensen</surname><given-names>R</given-names></name><name name-style="western"><surname>Brinck</surname><given-names>T</given-names></name><name name-style="western"><surname>Olesen</surname><given-names>J.</given-names></name></person-group><article-title>Sodium valproate has prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study</article-title>. <source>Neurology</source><year>1994</year>; <volume>44</volume>:<fpage>241</fpage>–<lpage>4</lpage>.</citation></ref><ref id="bibr20-j.1468-2982.2006.01194.x"><label>20</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Mathew</surname><given-names>NT</given-names></name><name name-style="western"><surname>Saper</surname><given-names>JR</given-names></name><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name><name name-style="western"><surname>Rankin</surname><given-names>L</given-names></name><name name-style="western"><surname>Markley</surname><given-names>HG</given-names></name><name name-style="western"><surname>Solomon</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Migraine prophylaxis with divalproex</article-title>. <source>Arch Neurol</source><year>1995</year>; <volume>52</volume>:<fpage>281</fpage>–<lpage>6</lpage>.</citation></ref><ref id="bibr21-j.1468-2982.2006.01194.x"><label>21</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Klapper</surname><given-names>JA.</given-names></name></person-group><article-title>Divalproex sodium in migraine prophylaxis: a dose-controlled study</article-title>. <source>Cephalalgia</source><year>1997</year>; <volume>17</volume>:<fpage>103</fpage>–<lpage>8</lpage>.</citation></ref><ref id="bibr22-j.1468-2982.2006.01194.x"><label>22</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Hering</surname><given-names>R</given-names></name><name name-style="western"><surname>Kuritzky</surname><given-names>A.</given-names></name></person-group><article-title>Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo</article-title>. <source>Cephalalgia</source><year>1992</year>; <volume>12</volume>:<fpage>81</fpage>–<lpage>4</lpage>.</citation></ref><ref id="bibr23-j.1468-2982.2006.01194.x"><label>23</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Stellar</surname><given-names>S</given-names></name><name name-style="western"><surname>Ahrens</surname><given-names>SP</given-names></name><name name-style="western"><surname>Meibohm</surname><given-names>AR</given-names></name><name name-style="western"><surname>Reines</surname><given-names>SA.</given-names></name></person-group><article-title>Migraine prevention with timolol</article-title>. <source>JAMA</source><year>1984</year>; <volume>252</volume>:<fpage>2576</fpage>–<lpage>9</lpage>.</citation></ref><ref id="bibr24-j.1468-2982.2006.01194.x"><label>24</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Briggs</surname><given-names>RS</given-names></name><name name-style="western"><surname>Millac</surname><given-names>PA.</given-names></name></person-group><article-title>Timolol in migraine prophylaxis</article-title>. <source>Headache</source><year>1979</year>; <volume>19</volume>:<fpage>379</fpage>–<lpage>81</lpage>.</citation></ref><ref id="bibr25-j.1468-2982.2006.01194.x"><label>25</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Standnes</surname><given-names>B</given-names></name><name name-style="western"><surname>Kangasneimi</surname><given-names>P</given-names></name><name name-style="western"><surname>Hakkarainen</surname><given-names>H</given-names></name><name name-style="western"><surname>Olesen</surname><given-names>J.</given-names></name></person-group><article-title>Timolol vs propranolol vs placebo in common migraine prophylaxis: a double blind multicenter study</article-title>. <source>Acta Neurol Scand</source><year>1984</year>; <volume>69</volume>:<fpage>1</fpage>–<lpage>8</lpage>.</citation></ref><ref id="bibr26-j.1468-2982.2006.01194.x"><label>26</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Rolan</surname><given-names>P.</given-names></name></person-group><article-title>β-Adrenoceptor blocking drugs in migraine propohylaxis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>519</fpage>–<lpage>28</lpage>.</citation></ref><ref id="bibr27-j.1468-2982.2006.01194.x"><label>27</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Andersson</surname><given-names>P-G</given-names></name><name name-style="western"><surname>Dahl</surname><given-names>S</given-names></name><name name-style="western"><surname>Hansen</surname><given-names>JH</given-names></name><name name-style="western"><surname>Hansen</surname><given-names>PE</given-names></name><name name-style="western"><surname>Hedman</surname><given-names>C</given-names></name><name name-style="western"><surname>Kristensen</surname><given-names>TN</given-names></name><name name-style="western"><surname>de fine Olivarius</surname><given-names>B.</given-names></name></person-group><article-title>Prophylactic treatment of classical and non-classical migraine with metoprolol—a comparison with placebo</article-title>. <source>Cephalalgia</source><year>1983</year>; <volume>3</volume>:<fpage>207</fpage>–<lpage>12</lpage>.</citation></ref><ref id="bibr28-j.1468-2982.2006.01194.x"><label>28</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Kangasneimi</surname><given-names>P</given-names></name><name name-style="western"><surname>Andersen</surname><given-names>AR</given-names></name><name name-style="western"><surname>Andersson</surname><given-names>PG</given-names></name><name name-style="western"><surname>Glihus</surname><given-names>NE</given-names></name><name name-style="western"><surname>Hedman</surname><given-names>C</given-names></name><name name-style="western"><surname>Hultgren</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Classic migraine: effective prophylaxis with metoprolol</article-title>. <source>Cephalalgia</source><year>1987</year>; <volume>7</volume>:<fpage>231</fpage>–<lpage>8</lpage>.</citation></ref><ref id="bibr29-j.1468-2982.2006.01194.x"><label>29</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Grotemeyer</surname><given-names>KH</given-names></name><name name-style="western"><surname>Scharafinski</surname><given-names>HW</given-names></name><name name-style="western"><surname>Schalke</surname><given-names>HP</given-names></name><name name-style="western"><surname>Hustedt</surname><given-names>IW.</given-names></name></person-group><article-title>Acetylsalicylic acid vs. metoprolol in migraine prophylaxis: double-blind crossover study</article-title>. <source>Headache</source><year>1990</year>; <volume>30</volume>:<fpage>639</fpage>–<lpage>41</lpage>.</citation></ref><ref id="bibr30-j.1468-2982.2006.01194.x"><label>30</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Steiner</surname><given-names>TJ</given-names></name><name name-style="western"><surname>Joseph</surname><given-names>R</given-names></name><name name-style="western"><surname>Hedman</surname><given-names>C</given-names></name><name name-style="western"><surname>Rose</surname><given-names>FC.</given-names></name></person-group><article-title>Metoprolol in the prophylaxis of migraine: parallel-groups comparison with placebo and dose-ranging follow-up</article-title>. <source>Headache</source><year>1988</year>; <volume>28</volume>:<fpage>15</fpage>–<lpage>23</lpage>.</citation></ref><ref id="bibr31-j.1468-2982.2006.01194.x"><label>31</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Kangasneimi</surname><given-names>P</given-names></name><name name-style="western"><surname>Headman</surname><given-names>C.</given-names></name></person-group><article-title>Metoprolol and propranolol in the prophylactic treatment of classical and common migraine: a double-blind study</article-title>. <source>Cephalalgia</source><year>1984</year>; <volume>4</volume>:<fpage>91</fpage>–<lpage>6</lpage>.</citation></ref><ref id="bibr32-j.1468-2982.2006.01194.x"><label>32</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P.</given-names></name></person-group><article-title>Efficacy of beta-blockers in migraine. A critical review</article-title>. <source>Cephalalgia</source><year>1986</year>; <volume>6</volume> (<supplement>Suppl. 5</supplement>):<fpage>15</fpage>–<lpage>24</lpage>.</citation></ref><ref id="bibr33-j.1468-2982.2006.01194.x"><label>33</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Toda</surname><given-names>N</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P.</given-names></name></person-group><article-title>Calcium antagonists in migraine prophylaxis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edition</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>539</fpage>–<lpage>44</lpage>.</citation></ref><ref id="bibr34-j.1468-2982.2006.01194.x"><label>34</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Saxena</surname><given-names>PR.</given-names></name></person-group><article-title>Antiserotonin drugs in migraine prophylaxis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ramadan</surname><given-names>NM</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Welch</surname><given-names>KMA</given-names></name></person-group> editors. <source>The headaches</source>, <edition>3rd edn</edition>. <publisher-loc>Philadelphia</publisher-loc>: <publisher-name>Lippincott Williams & Wilkins</publisher-name><year>2005</year>:<fpage>529</fpage>–<lpage>37</lpage>.</citation></ref><ref id="bibr35-j.1468-2982.2006.01194.x"><label>35</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Sommerville</surname><given-names>BW</given-names></name><name name-style="western"><surname>Hermann</surname><given-names>WM.</given-names></name></person-group><article-title>Migraine prophylaxis with lisuride hydrogen maleate. A double-blind study of lisuride versus placebo</article-title>. <source>Headache</source><year>1978</year>; <volume>18</volume>:<fpage>75</fpage>–<lpage>9</lpage>.</citation></ref><ref id="bibr36-j.1468-2982.2006.01194.x"><label>36</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Herman</surname><given-names>HW</given-names></name><name name-style="western"><surname>Kristof</surname><given-names>M</given-names></name><name name-style="western"><surname>Satre y Hernandez</surname><given-names>M.</given-names></name></person-group><article-title>Preventive treatment of migraine headache with a new isoergonyl derivative</article-title>. <source>J Intern Med Res</source><year>1978</year>; <volume>6</volume>:<fpage>476</fpage>–<lpage>82</lpage>.</citation></ref><ref id="bibr37-j.1468-2982.2006.01194.x"><label>37</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Aschcroft</surname><given-names>DM</given-names></name><name name-style="western"><surname>Millson</surname><given-names>D.</given-names></name></person-group><article-title>Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials</article-title>. <source>Pharmacoepidemiol Drug Saf</source><year>2004</year>; <volume>13</volume>:<fpage>73</fpage>–<lpage>82</lpage>.</citation></ref><ref id="bibr38-j.1468-2982.2006.01194.x"><label>38</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Ferrari</surname><given-names>MD</given-names></name><name name-style="western"><surname>Roon</surname><given-names>KI</given-names></name><name name-style="western"><surname>Lipton</surname><given-names>RB</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ.</given-names></name></person-group><article-title>Oral triptans (serotonin 5-HT<sub><sub>1B/!D</sub></sub> agonists) in acute migraine: a meta-analysis of 53 trials</article-title>. <source>Lancet</source><year>2001</year>; <volume>358</volume>:<fpage>1668</fpage>–<lpage>75</lpage>.</citation></ref><ref id="bibr39-j.1468-2982.2006.01194.x"><label>39</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Ferrari</surname><given-names>MD</given-names></name><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Roon</surname><given-names>KI</given-names></name><name name-style="western"><surname>Lipton</surname><given-names>RB.</given-names></name></person-group><article-title>Triptans (serotonin, 5-HT<sub><sub>1B/1D</sub></sub> agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials</article-title>. <source>Cephalalgia</source><year>2002</year>; <volume>22</volume>:<fpage>633</fpage>–<lpage>58</lpage>.</citation></ref><ref id="bibr40-j.1468-2982.2006.01194.x"><label>40</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Gawel</surname><given-names>MJ</given-names></name><name name-style="western"><surname>Worthington</surname><given-names>I</given-names></name><name name-style="western"><surname>Maggisano</surname><given-names>A.</given-names></name></person-group><article-title>A systematic review of the use of triptans in acute migraine</article-title>. <source>Can J Neurol Sci</source><year>2001</year>; <volume>28</volume>:<fpage>30</fpage>–<lpage>41</lpage>.</citation></ref><ref id="bibr41-j.1468-2982.2006.01194.x"><label>41</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Oldman</surname><given-names>AD</given-names></name><name name-style="western"><surname>Smith</surname><given-names>LA</given-names></name><name name-style="western"><surname>McQuay</surname><given-names>HJ</given-names></name><name name-style="western"><surname>Moore</surname><given-names>RA.</given-names></name></person-group><article-title>Pharmacological treatments for acute migraine: quantitative systematic review</article-title>. <source>Pain</source><year>2000</year>; <volume>97</volume>:<fpage>247</fpage>–<lpage>57</lpage>.</citation></ref><ref id="bibr42-j.1468-2982.2006.01194.x"><label>42</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Oldman</surname><given-names>AD</given-names></name><name name-style="western"><surname>Smith</surname><given-names>LA</given-names></name><name name-style="western"><surname>McQuay</surname><given-names>HJ</given-names></name><name name-style="western"><surname>Moore</surname><given-names>RA.</given-names></name></person-group><article-title>Rizatriptan for acute migraine</article-title>. <source>Cochrane Database Syst Rev</source><year>2001</year>; <volume>3</volume>:<fpage>CD003221</fpage>.</citation></ref><ref id="bibr43-j.1468-2982.2006.01194.x"><label>43</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Smith</surname><given-names>LA</given-names></name><name name-style="western"><surname>Oldman</surname><given-names>AD</given-names></name><name name-style="western"><surname>McQuay</surname><given-names>HJ</given-names></name><name name-style="western"><surname>Moore</surname><given-names>RA.</given-names></name></person-group><article-title>Eletriptan for acute migraine</article-title>. <source>Cochrane Database Syst Rev</source><year>2001</year>; <volume>3</volume>:<fpage>CD00324</fpage>.</citation></ref><ref id="bibr44-j.1468-2982.2006.01194.x"><label>44</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P.</given-names></name></person-group><article-title>Efficacy and adverse events of subcutaneous, oral and intranasal sumatriptan used for migraine treatment: a systematic review based on number needed to treat</article-title>. <source>Cephalalgia</source><year>1998</year>; <volume>18</volume>:<fpage>532</fpage>–<lpage>8</lpage>.</citation></ref><ref id="bibr45-j.1468-2982.2006.01194.x"><label>45</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>De Vries</surname><given-names>P</given-names></name><name name-style="western"><surname>Saxena</surname><given-names>PR.</given-names></name></person-group><article-title>Triptans in migraine. A comparative review of pharmacology, pharmacokinetics and efficacy</article-title>. <source>Drugs</source><year>2000</year>; <volume>60</volume>:<fpage>1259</fpage>–<lpage>87</lpage>.</citation></ref><ref id="bibr46-j.1468-2982.2006.01194.x"><label>46</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>McCrory</surname><given-names>D</given-names></name><name name-style="western"><surname>Gray</surname><given-names>RN.</given-names></name></person-group><article-title>Oral sumatriptan for acute migraine</article-title>. <source>Cochrane Database Syst Rev</source><year>2003</year>; <volume>3</volume>:<fpage>CD002915</fpage>.</citation></ref><ref id="bibr47-j.1468-2982.2006.01194.x"><label>47</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Linde</surname><given-names>K</given-names></name><name name-style="western"><surname>Rossnagel</surname><given-names>K.</given-names></name></person-group><article-title>Propranolol for migraine prophylaxis</article-title>. <source>Cochrane Database Syst Rev</source><year>2004</year>; <volume>2</volume>:<fpage>CD003225</fpage>.</citation></ref><ref id="bibr48-j.1468-2982.2006.01194.x"><label>48</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Pittler</surname><given-names>MH</given-names></name><name name-style="western"><surname>Ernst</surname><given-names>E.</given-names></name></person-group><article-title>Feverfew for preventing migraine</article-title>. <source>Cochrane Database Syst Rev</source><year>2004</year>; <volume>1</volume>:<fpage>CD002286</fpage>.</citation></ref><ref id="bibr49-j.1468-2982.2006.01194.x"><label>49</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Chronicle</surname><given-names>E</given-names></name><name name-style="western"><surname>Mulleners</surname><given-names>W.</given-names></name></person-group><article-title>Anticonvulsant drugs for migraine prophylaxis</article-title>. <source>Cochrane Database Syst Rev</source><year>2004</year>; <volume>3</volume>:<fpage>CD003226</fpage>.</citation></ref><ref id="bibr50-j.1468-2982.2006.01194.x"><label>50</label><citation citation-type="journal" xlink:type="simple"><collab xlink:type="simple">Headache Classification Committee of the International Headache Society.</collab><article-title>Classicification and diagnostic criteria for headache disorders, cranial neuralgies and facial pain</article-title>. <source>Cephalalgia</source><year>1988</year>; <volume>8</volume> (<supplement>Suppl. 7</supplement>):<fpage>1</fpage>–<lpage>96</lpage>.</citation></ref><ref id="bibr51-j.1468-2982.2006.01194.x"><label>51</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Moore</surname><given-names>RA</given-names></name><name name-style="western"><surname>Gavaghan</surname><given-names>D</given-names></name><name name-style="western"><surname>Tramer</surname><given-names>MR</given-names></name><name name-style="western"><surname>Collins</surname><given-names>SL</given-names></name><name name-style="western"><surname>McQuay</surname><given-names>HJ.</given-names></name></person-group><article-title>Size is everything—large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects</article-title>. <source>Pain</source><year>1998</year>; <volume>78</volume>:<fpage>209</fpage>–<lpage>16</lpage>.</citation></ref><ref id="bibr52-j.1468-2982.2006.01194.x"><label>52</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Winner</surname><given-names>P</given-names></name><name name-style="western"><surname>Mannix</surname><given-names>LK</given-names></name><name name-style="western"><surname>Putman</surname><given-names>DG</given-names></name><name name-style="western"><surname>McNeal</surname><given-names>S</given-names></name><name name-style="western"><surname>Kwong</surname><given-names>J</given-names></name><name name-style="western"><surname>O’Quinn</surname><given-names>S</given-names></name><name name-style="western"><surname>Richardson</surname><given-names>MS.</given-names></name></person-group><article-title>Pain-free results with sumatriptan taken at the first sign of migraine pain; 2 randomized, double-blind, placebo-controlled studies</article-title>. <source>Mayo Clin Proc</source><year>2003</year>; <volume>78</volume>:<fpage>1214</fpage>–<lpage>22</lpage>.</citation></ref><ref id="bibr53-j.1468-2982.2006.01194.x"><label>53</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Kramer</surname><given-names>MS</given-names></name><name name-style="western"><surname>Matzura-Wolfe</surname><given-names>D</given-names></name><name name-style="western"><surname>Polis</surname><given-names>A</given-names></name><name name-style="western"><surname>Getson</surname><given-names>A</given-names></name><name name-style="western"><surname>Amaraneni</surname><given-names>PG</given-names></name><name name-style="western"><surname>Solbach</surname><given-names>MP</given-names></name><etal></etal></person-group><article-title>A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks</article-title>. <source>Neurology</source><year>1998</year>; <volume>51</volume>:<fpage>773</fpage>–<lpage>81</lpage>.</citation></ref><ref id="bibr54-j.1468-2982.2006.01194.x"><label>54</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Teall</surname><given-names>J</given-names></name><name name-style="western"><surname>Rodriguez</surname><given-names>F</given-names></name><name name-style="western"><surname>Giacovazzo</surname><given-names>M</given-names></name><name name-style="western"><surname>Paz</surname><given-names>J</given-names></name><name name-style="western"><surname>Malbecq</surname><given-names>W</given-names></name></person-group><collab xlink:type="simple">et al. on behalf of the Rizatriptan 030 Study Group.</collab><article-title>Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine</article-title>. <source>Headache</source><year>1998</year>; <volume>38</volume>:<fpage>748</fpage>–<lpage>55</lpage>.</citation></ref><ref id="bibr55-j.1468-2982.2006.01194.x"><label>55</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Goldstein</surname><given-names>J</given-names></name><name name-style="western"><surname>Ryan</surname><given-names>R</given-names></name><name name-style="western"><surname>Jiang</surname><given-names>K</given-names></name><name name-style="western"><surname>Getson</surname><given-names>A</given-names></name><name name-style="western"><surname>Norman</surname><given-names>B</given-names></name><name name-style="western"><surname>Glock</surname><given-names>GA</given-names></name><name name-style="western"><surname>Lines</surname><given-names>C</given-names></name></person-group>; <collab xlink:type="simple">The Rizatriptan Protocol 046 Study Group.</collab><article-title>Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine</article-title>. <source>Headache</source><year>1998</year>; <volume>38</volume>:<fpage>737</fpage>–<lpage>47</lpage>.</citation></ref><ref id="bibr56-j.1468-2982.2006.01194.x"><label>56</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Kolodny</surname><given-names>A</given-names></name><name name-style="western"><surname>Polis</surname><given-names>A</given-names></name><name name-style="western"><surname>Battisti</surname><given-names>W</given-names></name><name name-style="western"><surname>Johnson-Pratt</surname><given-names>L</given-names></name><name name-style="western"><surname>Skobieranda</surname><given-names>F</given-names></name></person-group>; <collab xlink:type="simple">The Rizatriptan Protocol 052 Study Group.</collab><article-title>Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets</article-title>. <source>Cephalagia</source><year>2004</year>; <volume>24</volume>:<fpage>540</fpage>–<lpage>6</lpage>.</citation></ref><ref id="bibr57-j.1468-2982.2006.01194.x"><label>57</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Mathew</surname><given-names>NT</given-names></name><name name-style="western"><surname>Schoenen</surname><given-names>L</given-names></name><name name-style="western"><surname>Winner</surname><given-names>P</given-names></name><name name-style="western"><surname>Muirhead</surname><given-names>N</given-names></name><name name-style="western"><surname>Sikes</surname><given-names>CR.</given-names></name></person-group><article-title>Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg</article-title>. <source>Headache</source><year>2003</year>; <volume>43</volume>:<fpage>214</fpage>–<lpage>22</lpage>.</citation></ref><ref id="bibr58-j.1468-2982.2006.01194.x"><label>58</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Goadsby</surname><given-names>PJ</given-names></name><name name-style="western"><surname>Ferrari</surname><given-names>MD</given-names></name><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Stovner</surname><given-names>LJ</given-names></name><name name-style="western"><surname>Senard</surname><given-names>JM</given-names></name><name name-style="western"><surname>Jackson</surname><given-names>NC</given-names></name><name name-style="western"><surname>Poole</surname><given-names>PH</given-names></name></person-group>, <collab xlink:type="simple">Eletriptan Steering Committee.</collab><article-title>Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan</article-title>. <source>Neurology</source><year>2000</year>; <volume>54</volume>:<fpage>156</fpage>–<lpage>63</lpage>.</citation></ref><ref id="bibr59-j.1468-2982.2006.01194.x"><label>59</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Sandrini</surname><given-names>G</given-names></name><name name-style="western"><surname>Färkilä</surname><given-names>M</given-names></name><name name-style="western"><surname>Burgess</surname><given-names>G</given-names></name><name name-style="western"><surname>Forster</surname><given-names>E</given-names></name><name name-style="western"><surname>Haughie</surname><given-names>S.</given-names></name></person-group><article-title>Eletriptan vs. sumatriptan: a double-blind, placebo-controlled, multiple migraine attack study</article-title>. <source>Neurology</source><year>2002</year>; <volume>59</volume>:<fpage>1210</fpage>–<lpage>7</lpage>.</citation></ref><ref id="bibr60-j.1468-2982.2006.01194.x"><label>60</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Diener</surname><given-names>HC</given-names></name><name name-style="western"><surname>Ryan</surname><given-names>R</given-names></name><name name-style="western"><surname>Sun</surname><given-names>W</given-names></name><name name-style="western"><surname>Hettiarachchi</surname><given-names>J.</given-names></name></person-group><article-title>The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg</article-title>. <source>Eur J Neurol</source><year>2004</year>; <volume>11</volume>:<fpage>125</fpage>–<lpage>34</lpage>.</citation></ref><ref id="bibr61-j.1468-2982.2006.01194.x"><label>61</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Fuseau</surname><given-names>E</given-names></name><name name-style="western"><surname>Petricoul</surname><given-names>O</given-names></name><name name-style="western"><surname>Sabin</surname><given-names>A</given-names></name><name name-style="western"><surname>Pereira</surname><given-names>A</given-names></name><name name-style="western"><surname>O’Quin</surname><given-names>S</given-names></name><name name-style="western"><surname>Thein</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine attack</article-title>. <source>Clin Ther</source><year>2001</year>; <volume>23</volume>:<fpage>242</fpage>–<lpage>51</lpage>.</citation></ref><ref id="bibr62-j.1468-2982.2006.01194.x"><label>62</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Spierings</surname><given-names>ELH</given-names></name><name name-style="western"><surname>Gomez-Mancilla</surname><given-names>B</given-names></name><name name-style="western"><surname>Grosz</surname><given-names>D</given-names></name><name name-style="western"><surname>Rowland</surname><given-names>CR</given-names></name><name name-style="western"><surname>Whaley</surname><given-names>FS</given-names></name><name name-style="western"><surname>Jirgens</surname><given-names>KJ.</given-names></name></person-group><article-title>Oral almotriptan vs oralsumatriptan in the abortive treatment of migraine. A double-blind, randomized, parallel-group, optimum-dose comparison</article-title>. <source>Arch Neurol</source><year>2001</year>; <volume>58</volume>:<fpage>944</fpage>–<lpage>50</lpage>.</citation></ref><ref id="bibr63-j.1468-2982.2006.01194.x"><label>63</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Cabarrocas</surname><given-names>X.</given-names></name></person-group><article-title>Reply to Tfelt-Hansen</article-title>. <source>Cephalalgia</source><year>2004</year>; <volume>24</volume>:<fpage>688</fpage>–<lpage>9</lpage>.</citation></ref><ref id="bibr64-j.1468-2982.2006.01194.x"><label>64</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Dowson</surname><given-names>AJ</given-names></name><name name-style="western"><surname>Massiou</surname><given-names>H</given-names></name><name name-style="western"><surname>Lainez</surname><given-names>JM</given-names></name><name name-style="western"><surname>Cabarrocas</surname><given-names>X.</given-names></name></person-group><article-title>Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clnical trial</article-title>. <source>Cephalalgia</source><year>2002</year>; <volume>22</volume>:<fpage>453</fpage>–<lpage>61</lpage>.</citation></ref><ref id="bibr65-j.1468-2982.2006.01194.x"><label>65</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Sheftell</surname><given-names>FD</given-names></name><name name-style="western"><surname>Dahlof</surname><given-names>CG</given-names></name><name name-style="western"><surname>Brandes</surname><given-names>JL</given-names></name><name name-style="western"><surname>Agosti</surname><given-names>R</given-names></name><name name-style="western"><surname>Jones</surname><given-names>MW</given-names></name><name name-style="western"><surname>Barrett</surname><given-names>PS.</given-names></name></person-group><article-title>Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets</article-title>. <source>Clin Therapeutics</source><year>2005</year>; <volume>27</volume>:<fpage>407</fpage>–<lpage>17</lpage>.</citation></ref><ref id="bibr66-j.1468-2982.2006.01194.x"><label>66</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Brandes</surname><given-names>JL</given-names></name><name name-style="western"><surname>Saper</surname><given-names>JR</given-names></name><name name-style="western"><surname>Diamond</surname><given-names>M</given-names></name><name name-style="western"><surname>Couch</surname><given-names>JR</given-names></name><name name-style="western"><surname>Lewis</surname><given-names>DW</given-names></name><name name-style="western"><surname>Schmitt</surname><given-names>J</given-names></name><etal></etal></person-group>; <comment>MIGR-002 Study Group.</comment><article-title>Topiramate for migraine prevention: a randomized controlled trial</article-title>. <source>JAMA</source><year>2004</year>; <volume>291</volume>:<fpage>965</fpage>–<lpage>73</lpage>.</citation></ref><ref id="bibr67-j.1468-2982.2006.01194.x"><label>67</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Diener</surname><given-names>HC</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Dahlöf</surname><given-names>C</given-names></name><name name-style="western"><surname>Lainez</surname><given-names>MJA</given-names></name><name name-style="western"><surname>Sandrini</surname><given-names>G</given-names></name><name name-style="western"><surname>Wang</surname><given-names>S-J</given-names></name><etal></etal></person-group><article-title>Topiramate in migraine prophylaxis. Results from a placebo-controlled trial with propranolol as an active control</article-title>. <source>Eur Neurol</source><year>2004</year>; <volume>251</volume>:<fpage>953</fpage>–<lpage>0</lpage>.</citation></ref><ref id="bibr68-j.1468-2982.2006.01194.x"><label>68</label><citation citation-type="journal" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Silberstein</surname><given-names>SD</given-names></name><name name-style="western"><surname>Neto</surname><given-names>W</given-names></name><name name-style="western"><surname>Schmitt</surname><given-names>J</given-names></name><name name-style="western"><surname>Jacobs</surname><given-names>D</given-names></name></person-group>; <comment>MIGR-001 Study Group</comment>. <article-title>Topiramate in migraine prevention: results of a large controlled trial</article-title>. <source>Arch Neurol</source><year>2004</year>; <volume>61</volume>:<fpage>490</fpage>–<lpage>5</lpage>.</citation></ref><ref id="bibr69-j.1468-2982.2006.01194.x"><label>69</label><citation citation-type="book" xlink:type="simple"><person-group person-group-type="author"><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name><name name-style="western"><surname>Schoenen</surname><given-names>J</given-names></name><name name-style="western"><surname>Lauret</surname><given-names>D.</given-names></name></person-group><article-title>Success rates of combined oral lysine acetylsalicylate and metoclopramide, oral sumatriptan, and placebo depend on initial headache severity. A preliminary retrospective analysis</article-title>. <comment>In</comment>: <person-group person-group-type="editor"><name name-style="western"><surname>Olesen</surname><given-names>J</given-names></name><name name-style="western"><surname>Tfelt-Hansen</surname><given-names>P</given-names></name></person-group> editors. <source>6th International Headache Research Seminar. Headache Treatment. Trial Methodology and New Drugs</source>. <publisher-loc>New York</publisher-loc>: <publisher-name>Lippincott-Raven</publisher-name><year>1997</year>:<fpage>103</fpage>–<lpage>6</lpage>.</citation></ref></ref-list></back></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>A Review of Evidence-Based Medicine and Meta-Analytic Reviews in Migraine</title></titleInfo><name type="personal"><namePart type="given">P</namePart><namePart type="family">Tfelt-Hansen</namePart><affiliation>P. Tfelt-Hansen MD, Dr Med Sci, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark.</affiliation><affiliation>E-mail: tfelt@inet.uni2.dk</affiliation></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="review-article"></genre><originInfo><publisher>SAGE Publications</publisher><place><placeTerm type="text">Sage UK: London, England</placeTerm></place><dateIssued encoding="w3cdtf">2006</dateIssued><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the ‘gold standard’ and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.</abstract><subject><genre>keywords</genre><topic>Migraine</topic><topic>triptans</topic><topic>systematic review</topic><topic>meta-analysis</topic><topic>head-to-head comparison</topic></subject><relatedItem type="host"><titleInfo><title>Cephalalgia</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0333-1024</identifier><identifier type="eISSN">1468-2982</identifier><identifier type="PublisherID">CEP</identifier><identifier type="PublisherID-hwp">spcep</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>1265</start><end>1274</end></extent></part></relatedItem><identifier type="istex">B165AE08A0A963838CA3C6B15DC5BC82A49ED12F</identifier><identifier type="DOI">10.1111/j.1468-2982.2006.01194.x</identifier><identifier type="ArticleID">10.1111_j.1468-2982.2006.01194.x</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2006 International Headache Society</accessCondition><recordInfo><recordContentSource>SAGE</recordContentSource><recordOrigin>International Headache Society</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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