Topiramate: the evidence for its therapeutic value in the prevention of migraine
Identifieur interne : 000199 ( Ncbi/Merge ); précédent : 000198; suivant : 000200Topiramate: the evidence for its therapeutic value in the prevention of migraine
Auteurs : Carole NadinSource :
- Core Evidence [ 1555-1741 ] ; 2005.
Abstract
Preventive therapy is recommended in patients with migraines frequent and/or severe enough to interfere with daily life, and/or with an inadequate response to acute therapy (26–43% of patients with migraine in a recent US survey). Preventive treatments include beta blockers, amitriptyline, and antiepileptics (sodium valproate, gabapentin), but these may have significant adverse effects and are contraindicated in some patients. Topiramate is an antiepileptic recently approved for prevention of migraine.
To assess the evidence on the therapeutic value of topiramate as preventive treatment for migraine in adults.
All identified outcomes were patient-oriented. Strong evidence shows that topiramate 100 or 200 mg/day is more effective than placebo in reducing mean monthly migraine frequency, and further evidence shows better effectiveness than placebo on responder rate, rescue medication use, migraine severity, and migraine duration. The 100 mg/day dose appears generally better tolerated than 200 mg/day. Evidence shows that topiramate is associated with weight loss rather than weight gain. Limited evidence suggests that topiramate can improve health-related quality of life and reduce days with disability. Uncontrolled studies indicate effectiveness in refractory migraine. Limited evidence indicates broadly similar efficacy and tolerability for topiramate 100 mg/day and propranolol 160 mg/day, though more comparative trials are required. There is insufficient economic evidence to assess the cost effectiveness of topiramate.
Topiramate 100 mg/day is the dose with the best balance between efficacy and tolerability, and offers therapeutic value in patients in whom propranolol or other preventive migraine therapies are contraindicated, poorly tolerated, or ineffective.
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PubMed: 22500148
PubMed Central: 3321662
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PMC:3321662Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Topiramate: the evidence for its therapeutic value in the prevention of migraine</title>
<author><name sortKey="Nadin, Carole" sort="Nadin, Carole" uniqKey="Nadin C" first="Carole" last="Nadin">Carole Nadin</name>
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<series><title level="j">Core Evidence</title>
<idno type="ISSN">1555-1741</idno>
<idno type="eISSN">1555-175X</idno>
<imprint><date when="2005">2005</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Introduction:</title>
<p>Preventive therapy is recommended in patients with migraines frequent and/or severe enough to interfere with daily life, and/or with an inadequate response to acute therapy (26–43% of patients with migraine in a recent US survey). Preventive treatments include beta blockers, amitriptyline, and antiepileptics (sodium valproate, gabapentin), but these may have significant adverse effects and are contraindicated in some patients. Topiramate is an antiepileptic recently approved for prevention of migraine.</p>
</sec>
<sec><title>Aims:</title>
<p>To assess the evidence on the therapeutic value of topiramate as preventive treatment for migraine in adults.</p>
</sec>
<sec><title>Evidence review:</title>
<p>All identified outcomes were patient-oriented. Strong evidence shows that topiramate 100 or 200 mg/day is more effective than placebo in reducing mean monthly migraine frequency, and further evidence shows better effectiveness than placebo on responder rate, rescue medication use, migraine severity, and migraine duration. The 100 mg/day dose appears generally better tolerated than 200 mg/day. Evidence shows that topiramate is associated with weight loss rather than weight gain. Limited evidence suggests that topiramate can improve health-related quality of life and reduce days with disability. Uncontrolled studies indicate effectiveness in refractory migraine. Limited evidence indicates broadly similar efficacy and tolerability for topiramate 100 mg/day and propranolol 160 mg/day, though more comparative trials are required. There is insufficient economic evidence to assess the cost effectiveness of topiramate.</p>
</sec>
<sec><title>Place in therapy:</title>
<p>Topiramate 100 mg/day is the dose with the best balance between efficacy and tolerability, and offers therapeutic value in patients in whom propranolol or other preventive migraine therapies are contraindicated, poorly tolerated, or ineffective.</p>
</sec>
</div>
</front>
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</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Core Evid</journal-id>
<journal-id journal-id-type="iso-abbrev">Core Evid</journal-id>
<journal-id journal-id-type="publisher-id">Core Evidence</journal-id>
<journal-title-group><journal-title>Core Evidence</journal-title>
</journal-title-group>
<issn pub-type="ppub">1555-1741</issn>
<issn pub-type="epub">1555-175X</issn>
<publisher><publisher-name>Dove Medical Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22500148</article-id>
<article-id pub-id-type="pmc">3321662</article-id>
<article-id pub-id-type="publisher-id">ce-1-103</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Place in Therapy Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Topiramate: the evidence for its therapeutic value in the prevention of migraine</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Nadin</surname>
<given-names>Carole</given-names>
</name>
<xref ref-type="corresp" rid="c1-ce-1-103"></xref>
</contrib>
<aff id="af1-ce-1-103">Core Medical Publishing, Knutsford, UK</aff>
</contrib-group>
<author-notes><corresp id="c1-ce-1-103">Correspondence: Carole Nadin, Core Medical Publishing, Mere House, Brook Street, Knutsford, Cheshire WA16 8GP, UK or at <email>editor@coreevidence.com</email>
</corresp>
</author-notes>
<pub-date pub-type="collection"><year>2005</year>
</pub-date>
<pmc-comment>Dove Press titles changed from ppub to collections in 2009.
Fake ppub written to satisfy Coll Date Type=ppub</pmc-comment>
<pub-date pub-type="ppub"><year>2005</year>
</pub-date>
<pub-date pub-type="epub"><day>30</day>
<month>6</month>
<year>2005</year>
</pub-date>
<volume>1</volume>
<issue>2</issue>
<fpage>103</fpage>
<lpage>124</lpage>
<permissions><copyright-statement>© 2005 Dove Medical Press Limited. All rights reserved</copyright-statement>
<copyright-year>2005</copyright-year>
</permissions>
<abstract><sec><title>Introduction:</title>
<p>Preventive therapy is recommended in patients with migraines frequent and/or severe enough to interfere with daily life, and/or with an inadequate response to acute therapy (26–43% of patients with migraine in a recent US survey). Preventive treatments include beta blockers, amitriptyline, and antiepileptics (sodium valproate, gabapentin), but these may have significant adverse effects and are contraindicated in some patients. Topiramate is an antiepileptic recently approved for prevention of migraine.</p>
</sec>
<sec><title>Aims:</title>
<p>To assess the evidence on the therapeutic value of topiramate as preventive treatment for migraine in adults.</p>
</sec>
<sec><title>Evidence review:</title>
<p>All identified outcomes were patient-oriented. Strong evidence shows that topiramate 100 or 200 mg/day is more effective than placebo in reducing mean monthly migraine frequency, and further evidence shows better effectiveness than placebo on responder rate, rescue medication use, migraine severity, and migraine duration. The 100 mg/day dose appears generally better tolerated than 200 mg/day. Evidence shows that topiramate is associated with weight loss rather than weight gain. Limited evidence suggests that topiramate can improve health-related quality of life and reduce days with disability. Uncontrolled studies indicate effectiveness in refractory migraine. Limited evidence indicates broadly similar efficacy and tolerability for topiramate 100 mg/day and propranolol 160 mg/day, though more comparative trials are required. There is insufficient economic evidence to assess the cost effectiveness of topiramate.</p>
</sec>
<sec><title>Place in therapy:</title>
<p>Topiramate 100 mg/day is the dose with the best balance between efficacy and tolerability, and offers therapeutic value in patients in whom propranolol or other preventive migraine therapies are contraindicated, poorly tolerated, or ineffective.</p>
</sec>
</abstract>
<kwd-group><kwd>migraine</kwd>
<kwd>prophylaxis</kwd>
<kwd>topiramate</kwd>
<kwd>evidence</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><table-wrap id="t1-ce-1-103" position="float"><label>Table 1</label>
<caption><p>Evidence base included in the review</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="bottom" rowspan="2" colspan="1"><bold>Category</bold>
</th>
<th colspan="2" align="center" valign="bottom" rowspan="1"><bold>Number of records</bold>
<hr></hr>
</th>
</tr>
<tr><th align="center" valign="bottom" rowspan="1" colspan="1"><bold>Full papers</bold>
</th>
<th align="center" valign="bottom" rowspan="1" colspan="1"><bold>Abstracts</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Initial search</td>
<td align="center" valign="top" rowspan="1" colspan="1">142</td>
<td align="center" valign="top" rowspan="1" colspan="1">21</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> records excluded</td>
<td align="center" valign="top" rowspan="1" colspan="1">125</td>
<td align="center" valign="top" rowspan="1" colspan="1">14</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> records included</td>
<td align="center" valign="top" rowspan="1" colspan="1">17</td>
<td align="center" valign="top" rowspan="1" colspan="1">7</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Additional studies identified</td>
<td align="center" valign="top" rowspan="1" colspan="1">1</td>
<td align="center" valign="top" rowspan="1" colspan="1">n/a</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Search update, new records</td>
<td align="center" valign="top" rowspan="1" colspan="1">40</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> records excluded</td>
<td align="center" valign="top" rowspan="1" colspan="1">38</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> records included</td>
<td align="center" valign="top" rowspan="1" colspan="1">2</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Publications not available on databases and supplied by manufacturer</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
<td align="center" valign="top" rowspan="1" colspan="1">9</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Level 1 clinical evidence (systematic review, meta analysis)</td>
<td align="center" valign="top" rowspan="1" colspan="1">1</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Level 2 clinical evidence (RCT)</td>
<td align="center" valign="top" rowspan="1" colspan="1">8</td>
<td align="center" valign="top" rowspan="1" colspan="1">12</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Level ≥3 clinical evidence</td>
<td align="center" valign="top" rowspan="1" colspan="1">10</td>
<td align="center" valign="top" rowspan="1" colspan="1">3</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> trials other than RCT</td>
<td align="center" valign="top" rowspan="1" colspan="1">8</td>
<td align="center" valign="top" rowspan="1" colspan="1">3</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> case reports</td>
<td align="center" valign="top" rowspan="1" colspan="1">2</td>
<td align="center" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Economic evidence</td>
<td align="center" valign="top" rowspan="1" colspan="1">1</td>
<td align="center" valign="top" rowspan="1" colspan="1">1</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Total records included</td>
<td align="center" valign="top" rowspan="1" colspan="1">20</td>
<td align="center" valign="top" rowspan="1" colspan="1">16</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn1-ce-1-103"><p>For definition of levels of evidence, see Editorial Information on inside back cover.</p>
</fn>
<fn><p>RCT, randomized controlled trial.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t2-ce-1-103" position="float"><label>Table 2</label>
<caption><p>Definition and classification of the main types of migraine (adapted from <xref ref-type="bibr" rid="b39-ce-1-103">IHS 2004</xref>
)</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Migraine type</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Characteristics</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Migraine without aura</td>
<td align="left" valign="top" rowspan="1" colspan="1">At least five attacks not attributed to another disorder and fulfilling the following criteria:
<list list-type="bullet"><list-item><p>headache lasting 4–72 h if untreated or unsuccessfully treated</p>
</list-item>
<list-item><p>headache has at least two of the following features: unilateral location; pulsating quality; moderate or severe intensity; aggravation by, or causing avoidance of, routine physical activity (e.g. walking, climbing stairs)</p>
</list-item>
<list-item><p>during headache at least one of the following is also present: nausea and/or vomiting; photophobia and phonophobia</p>
</list-item>
</list>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Migraine with typical aura</td>
<td align="left" valign="top" rowspan="1" colspan="1">At least two attacks not attributed to another disorder and fulfilling the following criteria:
<list list-type="bullet"><list-item><p>aura consisting of at least one of the following but without motor weakness: fully reversible visual symptoms (e.g. flickering lights, spots, or lines; loss of vision); fully reversible sensory symptoms (e.g. pins and needles, numbness); fully reversible dysphasic speech disturbance</p>
</list-item>
<list-item><p>at least two of the following: homonymous visual symptoms and/or unilateral sensory symptoms; at least one aura symptom develops gradually over at least 5 min and/or different aura symptoms occur in succession over at least 5 min; each symptom lasts between 5 and 60 min</p>
</list-item>
<list-item><p>headache fulfilling the criteria for “Migraine without aura” begins during the aura or follows the aura within 60 min</p>
</list-item>
</list>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="t3-ce-1-103" position="float"><label>Table 3</label>
<caption><p>Cost burden of migraine</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1"><bold>Country</bold>
</th>
<th colspan="3" align="center" valign="top" rowspan="1"><bold>Cost of migraine per year</bold>
<hr></hr>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Reference</bold>
</th>
</tr>
<tr><th align="center" valign="top" rowspan="1" colspan="1"><bold>Direct</bold>
</th>
<th align="center" valign="top" rowspan="1" colspan="1"><bold>Indirect</bold>
</th>
<th align="center" valign="top" rowspan="1" colspan="1"><bold>Total</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">France</td>
<td align="left" valign="top" rowspan="1" colspan="1">€1044 million</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b59-ce-1-103">Pradalier et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Spain</td>
<td align="left" valign="top" rowspan="1" colspan="1">€344 million</td>
<td align="left" valign="top" rowspan="1" colspan="1">€732 million</td>
<td align="left" valign="top" rowspan="1" colspan="1">€1076 million</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b7-ce-1-103">Badia et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">USA</td>
<td align="left" valign="top" rowspan="1" colspan="1">$US1 billion</td>
<td align="left" valign="top" rowspan="1" colspan="1">$US13 billion</td>
<td align="left" valign="top" rowspan="1" colspan="1">$US14 billion</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b38-ce-1-103">Hu et al. 1999</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn2-ce-1-103"><p>NR, not reported.</p>
</fn>
<fn id="tfn3-ce-1-103"><p>Costs are given in the original currency. The average exchange rate in 2004 was €1 = $US1.24 (source: <ext-link ext-link-type="uri" xlink:href="www.fxtop.com">www.fxtop.com</ext-link>
)</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t4-ce-1-103" position="float"><label>Table 4</label>
<caption><p>Current therapy options recommended in migraine treatment guidelines</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"></th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold><xref ref-type="bibr" rid="b8-ce-1-103">BASH 2004</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold><xref ref-type="bibr" rid="b33-ce-1-103">Géraud et al. 2004</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold><xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
(US Headache Consortium)<xref ref-type="table-fn" rid="tfn4-ce-1-103">a</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold><xref ref-type="bibr" rid="b70-ce-1-103">Snow et al. 2002</xref>
(AAFP/ACP-ASIM)<xref ref-type="table-fn" rid="tfn5-ce-1-103">b</xref>
</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Acute treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">Simple analgesics with or without antiemetics<break></break>
Triptans<break></break>
Ergotamine</td>
<td align="left" valign="top" rowspan="1" colspan="1">NSAIDs alone or with metoclopramide<break></break>
Triptans<break></break>
Ergotamine</td>
<td align="left" valign="top" rowspan="1" colspan="1">Triptans<break></break>
Analgesics<break></break>
Metoclopramide<break></break>
Ergotamine</td>
<td align="left" valign="top" rowspan="1" colspan="1">NSAIDs<break></break>
Triptans<break></break>
Dihydroergotamine</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Criteria for preventive migraine treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">Inadequate symptom control with acute therapy<break></break>
Over-frequent use of acute therapy</td>
<td align="left" valign="top" rowspan="1" colspan="1">Severe, frequent and/or disabling migraine<break></break>
In patients taking 6–8 doses of acute medication per month for ≥3 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">Frequent headaches that interfere with daily life<break></break>
Contraindication, failure, overuse or intolerance of acute treatments<break></break>
Patient preference and cost<break></break>
Uncommon types of migraine</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 or more attacks per month producing 3 or more days of disability per month<break></break>
Contraindication, failure or overuse of acute treatments<break></break>
Uncommon types of migraine</td>
</tr>
<tr><td colspan="5" align="left" valign="top" rowspan="1"><bold>Preventive treatment</bold>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">First-line</td>
<td align="left" valign="top" rowspan="1" colspan="1">Beta blockers without partial agonist activity (atenolol, metoprolol, propranolol)<break></break>
Amitriptyline</td>
<td align="left" valign="top" rowspan="1" colspan="1">Propranolol, metoprolol<break></break>
Oxeterone<break></break>
Amitriptyline</td>
<td align="left" valign="top" rowspan="1" colspan="1">Amitriptyline<break></break>
Divalproex sodium<xref ref-type="table-fn" rid="tfn6-ce-1-103">c</xref>
<break></break>
Propranolol, timolol</td>
<td align="left" valign="top" rowspan="1" colspan="1">Propranolol, timolol<break></break>
Amitriptyline<break></break>
Divalproex sodium, sodium valproate</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Second-line</td>
<td align="left" valign="top" rowspan="1" colspan="1">Sodium valproate<break></break>
Topiramate</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pizotifen<break></break>
Flunarizine<break></break>
Sodium valproate<break></break>
Gabapentin<break></break>
Topiramate</td>
<td align="left" valign="top" rowspan="1" colspan="1">Atenolol, metoprolol, nadolol<break></break>
Calcium channel blockers (verapamil, nimodipine)<break></break>
NSAIDs<break></break>
Fluoxetine<break></break>
Gabapentin<break></break>
Feverfew, magnesium, vitamin B<sub>2</sub>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Flunarizine<break></break>
Lisuride<break></break>
Pizotifen<break></break>
Time-released dihydroergotamine<break></break>
Methysergide</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Third-line</td>
<td align="left" valign="top" rowspan="1" colspan="1">Gabapentin<break></break>
Methysergide</td>
<td align="left" valign="top" rowspan="1" colspan="1">Methysergide</td>
<td align="left" valign="top" rowspan="1" colspan="1">Antidepressants<break></break>
Cyproheptadine<break></break>
Diltiazem<break></break>
Ibuprofen<break></break>
Topiramate<break></break>
Phenelzine<break></break>
Methysergide</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn4-ce-1-103"><label>a</label>
<p>These guidelines classified medication into Group 1 (proven high efficacy and mild–moderate adverse events), Group 2 (lower efficacy and mild–moderate adverse events), Group 3 (use based on opinion), and Group 4 (proven efficacy but frequent or severe adverse events). Group 1 is listed here as first-line, group 2 as second-line, and groups 3 and 4 as third-line.</p>
</fn>
<fn id="tfn5-ce-1-103"><label>b</label>
<p>These guidelines classified medication into first-line agents and “other agents with proven efficacy but frequent or severe adverse events or limited published data on adverse events” (listed here as second-line).</p>
</fn>
<fn id="tfn6-ce-1-103"><label>c</label>
<p>Divalproex sodium (also called valproate semisodium) is a complex of sodium valproate and valproic acid in a 1:1 ratio.</p>
</fn>
<fn id="tfn7-ce-1-103"><p>AAFP, American Academy of Family Physicians; ACP-ASIM, American College of Physicians–American Society of Internal Medicine; BASH, British Association for Study of Headache; NSAID, nonsteroidal antiinflammatory drug.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t5-ce-1-103" position="float"><label>Table 5</label>
<caption><p>Current migraine preventive drugs (adapted from <xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
)</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Drug</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Effectiveness</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Adverse effects</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Contraindications</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Reference</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Divalproex sodium/sodium valproate<xref ref-type="table-fn" rid="tfn8-ce-1-103">a</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Divalproex sodium responders to treatment<xref ref-type="table-fn" rid="tfn9-ce-1-103">b</xref>
148/352 (42%)<break></break>
Sodium valproate responders to treatment<xref ref-type="table-fn" rid="tfn9-ce-1-103">b</xref>
17/34 (50%)<break></break>
Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
+++</td>
<td align="left" valign="top" rowspan="1" colspan="1">Occasional to frequent</td>
<td align="left" valign="top" rowspan="1" colspan="1">Liver disease, bleeding disorders</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Gabapentin</td>
<td align="left" valign="top" rowspan="1" colspan="1">Responders to treatment<xref ref-type="table-fn" rid="tfn9-ce-1-103">b</xref>
26/56 (46%)<break></break>
Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
++</td>
<td align="left" valign="top" rowspan="1" colspan="1">Occasional to frequent</td>
<td align="left" valign="top" rowspan="1" colspan="1">Liver disease, bleeding disorders</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Carbamazepine</td>
<td align="left" valign="top" rowspan="1" colspan="1">Responders to treatment<xref ref-type="table-fn" rid="tfn9-ce-1-103">b</xref>
26/45 (58%)<break></break>
Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
0</td>
<td align="left" valign="top" rowspan="1" colspan="1">Occasional to frequent</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Topiramate</td>
<td align="left" valign="top" rowspan="1" colspan="1">Responders to treatment<xref ref-type="table-fn" rid="tfn9-ce-1-103">b</xref>
132/264 (50%)<break></break>
Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
++</td>
<td align="left" valign="top" rowspan="1" colspan="1">Occasional to frequent</td>
<td align="left" valign="top" rowspan="1" colspan="1">Kidney stones</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Propranolol</td>
<td align="left" valign="top" rowspan="1" colspan="1">Responders to treatment<xref ref-type="table-fn" rid="tfn11-ce-1-103">d</xref>
77/114 (68%)<break></break>
Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
+++</td>
<td align="left" valign="top" rowspan="1" colspan="1">Infrequent to occasional<break></break>
Dropout rate due to AEs<xref ref-type="table-fn" rid="tfn12-ce-1-103">e</xref>
9/193 (4.7%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Asthma, depression, congestive heart failure, Raynaud’s disease, diabetes</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b47-ce-1-103">Linde & Rossnagel 2004</xref>
; <xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Amitriptyline</td>
<td align="left" valign="top" rowspan="1" colspan="1">Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
+++</td>
<td align="left" valign="top" rowspan="1" colspan="1">Frequent</td>
<td align="left" valign="top" rowspan="1" colspan="1">Mania, urinary retention, heart block</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Naproxen/naproxen sodium</td>
<td align="left" valign="top" rowspan="1" colspan="1">Clinical impression of effect<xref ref-type="table-fn" rid="tfn10-ce-1-103">c</xref>
+</td>
<td align="left" valign="top" rowspan="1" colspan="1">Infrequent</td>
<td align="left" valign="top" rowspan="1" colspan="1">Ulcer disease, gastritis</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b62-ce-1-103">Silberstein 2000</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">2004</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn8-ce-1-103"><label>a</label>
<p>Divalproex sodium (also called valproate semisodium) is a complex of sodium valproate and valproic acid in a 1:1 ratio.</p>
</fn>
<fn id="tfn9-ce-1-103"><label>b</label>
<p>Defined as patients with a 50% or greater reduction in migraine frequency compared with baseline. Number of events (patients who responded) and total number of patients presented in original source (<xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
).</p>
</fn>
<fn id="tfn10-ce-1-103"><label>c</label>
<p>Definitions as follows: 0, most people get no improvement; +, few people get clinically significant improvement; ++, some people get clinically significant improvement; +++, most people get clinically significant improvement.</p>
</fn>
<fn id="tfn11-ce-1-103"><label>d</label>
<p>Definition of response varied among the pooled trials. Data given here are for propranolol 160 mg/day. Number of events (patients who responded) and total number of patients presented in original source (<xref ref-type="bibr" rid="b47-ce-1-103">Linde & Rossnagel 2004</xref>
).</p>
</fn>
<fn id="tfn12-ce-1-103"><label>e</label>
<p>Data given here are for propranolol 160 mg/day. Number of events (patients who dropped out due to AEs) and total number of patients presented in original source (<xref ref-type="bibr" rid="b47-ce-1-103">Linde & Rossnagel 2004</xref>
).</p>
</fn>
<fn><p>AE, adverse event.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t6-ce-1-103" position="float"><label>Table 6</label>
<caption><p>Effects of topiramate on migraine frequency and number of patients responding to treatment (defined as a reduction of ≥50% in mean monthly migraine frequency)</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1"><bold>Level of evidence</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Design</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Treatment and target dose [median dose]</bold>
</th>
<th colspan="2" align="center" valign="top" rowspan="1"><bold>Outcome</bold>
<hr></hr>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Reference</bold>
</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Migraine frequency (mean no. of attacks/month)</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>% responders</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">1</td>
<td align="left" valign="top" rowspan="1" colspan="1">Systematic review and meta analysis of 3 RCTs</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo<break></break>
T 50 mg/day<break></break>
T 100 mg/day<break></break>
T 200 mg/day</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.0001)<break></break>
Lower with T 100 mg or 200 mg vs T 50 mg (<italic>P</italic>
<0.05)<break></break>
NSD T 50 mg vs placebo<break></break>
NSD T 100 mg vs 200 mg</td>
<td align="left" valign="top" rowspan="1" colspan="1">More responders with T 50 mg, 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.001)<break></break>
More responders with T 100 mg or 200 mg vs T 50 mg (<italic>P</italic>
<0.01)<break></break>
NSD T 100 mg vs 200 mg</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
<xref ref-type="table-fn" rid="tfn13-ce-1-103">a</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=73)<break></break>
T 200 mg/day [135 mg/day<xref ref-type="table-fn" rid="tfn14-ce-1-103">b</xref>
] (n=138)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NSD T vs placebo in ITT analysis<break></break>
In subgroup of patients with migraine with aura (approx. 1/3 of total), decrease from baseline with T (<italic>P</italic>
=0.018)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b31-ce-1-103">Freitag 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 2 double-blind single-center RCTs, 8–12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=36)<break></break>
T 200 mg/day (n=34)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower with T vs placebo (<italic>P</italic>
=0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1">More responders with T vs placebo (<italic>P</italic>
=0.008)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b28-ce-1-103">Edwards et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Multicenter RCT, 7 weeks double-blind followed by 11 weeks open-label</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day (n=117)<break></break>
T 100 mg/day (n=125)<break></break>
T 200 mg/day (n=112)<xref ref-type="table-fn" rid="tfn15-ce-1-103">c</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.001)<break></break>
NSD T 50 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">23% placebo<break></break>
35% T 50 mg<break></break>
54% T 100 mg<break></break>
52% T 200 mg<xref ref-type="table-fn" rid="tfn16-ce-1-103">d</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b63-ce-1-103">Silberstein 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind single-center RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=37)<break></break>
T 100 mg/day (n=35)<xref ref-type="table-fn" rid="tfn17-ce-1-103">e</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease with T vs placebo (<italic>P</italic>
<0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1">More responders with T vs placebo (<italic>P</italic>
<0.01)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b55-ce-1-103">Mei et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind RCT, 20 weeks, followed by open-label extension, 56 weeks, n=29 total</td>
<td align="left" valign="top" rowspan="1" colspan="1">T for 76 weeks of treatment<break></break>
Placebo for 20 weeks then T for 56 weeks<break></break>
Mean T dose during open-label phase, 127 mg/day</td>
<td align="left" valign="top" rowspan="1" colspan="1">Significant reduction in both groups (<italic>P</italic>
<0.01)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b36-ce-1-103">Hart et al. 2002</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=143)<break></break>
T 100 mg/day [87.9 mg/day] (n=139)<break></break>
T 200 mg/day [124.2 mg/day] (n=143)<break></break>
Propranolol 160 [129.6 mg/day] mg/day (n=143)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease with T 100 mg vs placebo (<italic>P</italic>
=0.011)<break></break>
NSD T 200 mg vs placebo<break></break>
Similar decrease for T 100 mg and propranolol<xref ref-type="table-fn" rid="tfn18-ce-1-103">f</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">More responders with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.05)<break></break>
Similar for T 100 mg or 200 mg and propranolol<xref ref-type="table-fn" rid="tfn18-ce-1-103">f</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b25-ce-1-103">Diener et al. 2004</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn13-ce-1-103"><label>a</label>
<p>The three trials included were <xref ref-type="bibr" rid="b12-ce-1-103">Brandes et al. 2004</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">Silberstein et al. 2004</xref>
, and <xref ref-type="bibr" rid="b73-ce-1-103">Storey et al. 2001</xref>
.</p>
</fn>
<fn id="tfn14-ce-1-103"><label>b</label>
<p>Mean dose.</p>
</fn>
<fn id="tfn15-ce-1-103"><label>c</label>
<p>Patient numbers unclear in the original as the numbers given in the figures (given here) do not match the numbers given in the text.</p>
</fn>
<fn id="tfn16-ce-1-103"><label>d</label>
<p>No between-group comparison reported.</p>
</fn>
<fn id="tfn17-ce-1-103"><label>e</label>
<p>Patients who completed the trial.</p>
</fn>
<fn id="tfn18-ce-1-103"><label>f</label>
<p>No between-group <italic>P</italic>
value reported, but 95% confidence intervals for the difference between topiramate and propranolol included zero, indicating comparable results. ITT, intention-to-treat; NR, not reported; NSD, not statistically significantly different; RCT, randomized controlled trial; T, topiramate.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t7-ce-1-103" position="float"><label>Table 7</label>
<caption><p>Effects of topiramate on number of monthly migraine days, rescue medication use, migraine severity, and migraine duration</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1"><bold>Level of evidence</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Design</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Treatment and target dose [median dose]</bold>
</th>
<th colspan="4" align="center" valign="top" rowspan="1"><bold>Outcome</bold>
<hr></hr>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Reference</bold>
</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Migraine days/month</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Rescue medication days</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Migraine duration</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Migraine severity</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=114)<break></break>
T 50 mg/day [46.5 mg/day] (n=117)<break></break>
T 100 mg/day [85.6 mg/day] (n=120)<break></break>
T 200 mg/day [150.2 mg/day] (n=117)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.01)<break></break>
NSD T 50 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.05)<break></break>
NSD T 50 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T 200 mg vs placebo (<italic>P</italic>
=0.007)<break></break>
NSD T 50 mg or 100 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower with T 100 mg vs placebo (<italic>P</italic>
=0.04)<break></break>
NSD T 50 mg or 200 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b12-ce-1-103">Brandes et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day [44.7 mg/day<xref ref-type="table-fn" rid="tfn19-ce-1-103">a</xref>
] (n=117)<break></break>
T 100 mg/day [78.3 mg/day<xref ref-type="table-fn" rid="tfn19-ce-1-103">a</xref>
] (n=125)<break></break>
T 200 mg/day [116.2 mg/day<xref ref-type="table-fn" rid="tfn19-ce-1-103">a</xref>
] (n=112)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.001)<break></break>
NSD T 50 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.01)<break></break>
NSD T 50 mg vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-ce-1-103">Silberstein et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=73)<break></break>
T 200 mg/day [135 mg/day<xref ref-type="table-fn" rid="tfn19-ce-1-103">a</xref>
] (n=138)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease from baseline with T (<italic>P</italic>
=0.016)<xref ref-type="table-fn" rid="tfn20-ce-1-103">b</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NSD T vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease 30% with T<break></break>
Increase 30% with placebo<xref ref-type="table-fn" rid="tfn20-ce-1-103">b</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease 7% with T<break></break>
Decrease 0.5% with placebo<xref ref-type="table-fn" rid="tfn20-ce-1-103">b</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b31-ce-1-103">Freitag 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Multicenter RCT, 7 weeks double-blind followed by 11 weeks open-label</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day (n=117)<break></break>
T 100 mg/day (n=125)<break></break>
T 200 mg/day (n=112)<xref ref-type="table-fn" rid="tfn21-ce-1-103">c</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline for T 100 mg or 200 mg vs placebo (<italic>P</italic>
<0.01)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b63-ce-1-103">Silberstein 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind single-center RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=37)<break></break>
T 100 mg/day (n=35)<xref ref-type="table-fn" rid="tfn22-ce-1-103">d</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease from baseline with T vs placebo (<italic>P</italic>
<0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b55-ce-1-103">Mei et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, single-center RCT, 8 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=21)<break></break>
T 200 mg/day [125 mg/day<xref ref-type="table-fn" rid="tfn19-ce-1-103">a</xref>
] (n=19)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NSD T vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b73-ce-1-103">Storey et al. 2001</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=143)<break></break>
T 100 mg/day [87.9 mg/day] (n=139)<break></break>
T 200 mg/day [124.2 mg/day] (n=143)<break></break>
Propranolol 160 [129.6 mg/day] mg/day (n=143)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease with T 100 mg vs placebo (<italic>P</italic>
=0.026)<break></break>
NSD T 200 mg vs placebo<break></break>
Similar decrease for T 100 mg or 200 mg and propranolol<xref ref-type="table-fn" rid="tfn23-ce-1-103">e</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Greater decrease with T 100 mg vs placebo (<italic>P</italic>
=0.029)<break></break>
NSD T 200 mg vs placebo<break></break>
Similar decrease for T 100 mg and propranolol<xref ref-type="table-fn" rid="tfn23-ce-1-103">e</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease from baseline 0.8 days for T 100 mg, 0.6 days for T 200 mg, 0.4 days for placebo<xref ref-type="table-fn" rid="tfn20-ce-1-103">b</xref>
<break></break>
NR for propranolol</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b25-ce-1-103">Diener et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Open survey, mean treatment duration 7 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">T up to 50 mg/day (n=102)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Reduction in % of patients reporting intense headaches (from 88% to 18%)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b40-ce-1-103">Kowacs et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Open longitudinal study, 6 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100 mg/day (n=12)<break></break>
Results after 6 months T treatment compared vs baseline</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">62% patients reported shorter headache duration with T</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower during T treatment (<italic>P</italic>
<0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b45-ce-1-103">Lampl et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective case series, mean treatment duration 149 days</td>
<td align="left" valign="top" rowspan="1" colspan="1">T mean dose 208 mg/day (n=74)<break></break>
Topiramate treatment period compared with previous treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower during T treatment (<italic>P</italic>
<0.0001)</td>
<td align="left" valign="top" rowspan="1" colspan="1">74% patients reported using less rescue medication during T treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">45–58% patients reported shorter headache duration during T treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lower during T treatment (<italic>P</italic>
<0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b81-ce-1-103">Young et al. 2002</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn19-ce-1-103"><label>a</label>
<p>Mean dose.</p>
</fn>
<fn id="tfn20-ce-1-103"><label>b</label>
<p>No between-group statistical comparison presented.</p>
</fn>
<fn id="tfn21-ce-1-103"><label>c</label>
<p>Patient numbers unclear in the original as the numbers given in the figures (given here) do not match the numbers given in the text.</p>
</fn>
<fn id="tfn22-ce-1-103"><label>d</label>
<p>Patients who completed the trial.</p>
</fn>
<fn id="tfn23-ce-1-103"><label>e</label>
<p>No between-group <italic>P</italic>
value reported, but 95% confidence intervals for the difference between topiramate and propranolol included zero, indicating comparable results.</p>
</fn>
<fn id="tfn24-ce-1-103"><p>NR, not reported; NSD, not statistically significantly different; RCT, randomized controlled trial; T, topiramate.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t8-ce-1-103" position="float"><label>Table 8</label>
<caption><p>Adverse events reported with topiramate</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1"><bold>Level of evidence</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Design</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Treatment and target dose [median dose]</bold>
</th>
<th colspan="7" align="center" valign="top" rowspan="1"><bold>Outcome</bold>
<hr></hr>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Reference</bold>
</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Paresthesia</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Anorexia</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Fatigue</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Nausea</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Altered taste</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Cognitive difficulty<xref ref-type="table-fn" rid="tfn25-ce-1-103">a</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Withdrawals due to AEs</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">1</td>
<td align="left" valign="top" rowspan="1" colspan="1">Systematic review and meta analysis of 3 RCTs</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo<break></break>
T 50 mg/day<break></break>
T 100 mg/day<break></break>
T 200 mg/day</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: 3.4<break></break>
T 100 mg: 2.4<break></break>
T 200 mg: 2.3</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: 30.5<break></break>
T 100 mg: 14.4<break></break>
T 200 mg: 11.3</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: 22.3<break></break>
T 100 mg: 32.9<break></break>
T 200 mg: 12.1</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: undefined<break></break>
T 100 mg: 29<break></break>
T 200 mg: 19.2</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: 6.9<break></break>
T 100 mg: 11.8<break></break>
T 200 mg: 6.7</td>
<td align="left" valign="top" rowspan="1" colspan="1">NNH:<break></break>
T 50 mg: 19.7<break></break>
T 100 mg: 14.1<break></break>
T 200 mg: 7.7</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 50 mg: 17%<break></break>
T 100 mg: 19–26%<break></break>
T 200 mg: 11–32%</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b17-ce-1-103">Chronicle & Mulleners 2004</xref>
<xref ref-type="table-fn" rid="tfn26-ce-1-103">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=73)<break></break>
T 200 mg/day [135 mg/day<xref ref-type="table-fn" rid="tfn27-ce-1-103">c</xref>
] (n=138)<xref ref-type="table-fn" rid="tfn28-ce-1-103">d</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 43%<break></break>
Placebo: NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 24%<break></break>
Placebo: NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 patients (total number of patients NR)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b31-ce-1-103">Freitag 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 2 double-blind single center RCTs, 8–12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=36)<break></break>
T 200 mg/day (n=34)</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 65%<break></break>
Placebo: 22%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 12%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 32%<break></break>
Placebo: 3%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 18%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 6/34<break></break>
Placebo: 0/36</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b28-ce-1-103">Edwards et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Multicenter RCT, 7 weeks double-blind followed by 11 weeks open-label</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day (n=117)<break></break>
T 100 mg/day (n=125)<break></break>
T 200 mg/day (n=112)<xref ref-type="table-fn" rid="tfn29-ce-1-103">e</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR<break></break>
5% of patients with paresthesia stopped treatment as a result</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Withdrawal:<break></break>
T 100: 2%<break></break>
T 200: 2%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b63-ce-1-103">Silberstein 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind single-center RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=37)<break></break>
T 100 mg/day (n=35)<xref ref-type="table-fn" rid="tfn30-ce-1-103">f</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 23%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 11%<break></break>
Placebo: 0</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 6%<break></break>
Placebo: 0</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 8%<break></break>
Placebo: 0</td>
<td align="left" valign="top" rowspan="1" colspan="1">T: 17/58<break></break>
P: 2/57</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b55-ce-1-103">Mei et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=143)<break></break>
T 100 mg/day [87.9 mg/day] (n=139)<break></break>
T 200 mg/day [124.2 mg/day] (n=143)<break></break>
Propranolol 160 [129.6 mg/day] mg/day (n=143)</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 55%<break></break>
T 200: 56%<break></break>
Propranolol: 12%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 17%<break></break>
T 200: 14%<break></break>
Propranolol: 3%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 19%<break></break>
T 200: 24%<break></break>
Propranolol: 22%<break></break>
Placebo: 15%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 13%<break></break>
T 200: 17%<break></break>
Propranolol: 13%<break></break>
Placebo: 8%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 5%<break></break>
T 200: 14%<break></break>
Propranolol: 0<break></break>
Placebo: 1%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 9%<break></break>
T 200: 15%<break></break>
Propranolol: 5%<break></break>
Placebo: 4%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 37/141<break></break>
T 200: 63/144<break></break>
Propranolol: 29/144<break></break>
Placebo: 15/146</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b25-ce-1-103">Diener et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 2 RCTs<xref ref-type="table-fn" rid="tfn31-ce-1-103">g</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo<break></break>
T 50 mg/day<break></break>
T 100 mg/day<break></break>
T 200 mg/day</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 48%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 13%<break></break>
Placebo: 6%</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 100: 13%<break></break>
Placebo: 10%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">T 50: 17%<break></break>
T 100: 23%<break></break>
T 200: 27%<break></break>
Placebo: 11%</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b37-ce-1-103">Hart et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 4 RCTs</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo<break></break>
T 50 mg/day<break></break>
T 100 mg/day<break></break>
T 200 mg/day<break></break>
n=1580 total</td>
<td align="left" valign="top" rowspan="1" colspan="1">Withdrawal:<break></break>
T: 7%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Withdrawal:<break></break>
T: 4%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Withdrawal:<break></break>
T: 4%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Withdrawal:<break></break>
T: 3%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b44-ce-1-103">Lainez et al. 2003</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn25-ce-1-103"><label>a</label>
<p>Definitions varied; terms included “language problems,” “memory impairment,” “difficulty with concentration.”</p>
</fn>
<fn id="tfn26-ce-1-103"><label>b</label>
<p>The three trials included were <xref ref-type="bibr" rid="b12-ce-1-103">Brandes et al. (2004)</xref>
, <xref ref-type="bibr" rid="b64-ce-1-103">Silberstein et al. (2004)</xref>
, and <xref ref-type="bibr" rid="b73-ce-1-103">Storey et al. (2001)</xref>
.</p>
</fn>
<fn id="tfn27-ce-1-103"><label>c</label>
<p>Mean dose.</p>
</fn>
<fn id="tfn28-ce-1-103"><label>d</label>
<p>Results refer to a subgroup of patients with migraine with aura, approximately 1/3 of the total.</p>
</fn>
<fn id="tfn29-ce-1-103"><label>e</label>
<p>Patient numbers unclear in the original as the numbers given in the figures (given here) do not match the numbers given in the text.</p>
</fn>
<fn id="tfn30-ce-1-103"><label>f</label>
<p>Number of patients completing the trial. The dropout rate results are given for the number of patients randomized.</p>
</fn>
<fn id="tfn31-ce-1-103"><label>g</label>
<p>The two trials were <xref ref-type="bibr" rid="b12-ce-1-103">Brandes et al. (2004)</xref>
and <xref ref-type="bibr" rid="b64-ce-1-103">Silberstein et al. (2004)</xref>
.</p>
</fn>
<fn id="tfn32-ce-1-103"><p>AE, adverse events; NNH, number needed to harm; NR, not reported; RCT, randomized controlled trial; T, topiramate.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t9-ce-1-103" position="float"><label>Table 9</label>
<caption><p>Effects of topiramate on weight in patients treated for migraine prophylaxis</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="2" colspan="1"><bold>Level of evidence</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Design</bold>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Treatment and target dose [median dose]</bold>
</th>
<th colspan="2" align="center" valign="top" rowspan="1"><bold>Outcome</bold>
<hr></hr>
</th>
<th align="left" valign="top" rowspan="2" colspan="1"><bold>Reference</bold>
</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Patients reporting weight loss (%)</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Mean weight change</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=114)<break></break>
T 50 mg/day [46.5 mg/day] (n=117)<break></break>
T 100 mg/day [85.6 mg/day] (n=120)<break></break>
T 200 mg/day [150.2 mg/day] (n=117)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: 3%<break></break>
T 50: 6%<break></break>
T 100: 11%<break></break>
T 200: 9%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: increase 0.2%<break></break>
T 50: decrease 2.2%<break></break>
T 100: decrease 3.3%<break></break>
T 200: decrease 4.6%<break></break>
All T <italic>P</italic>
<0.001 vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b12-ce-1-103">Brandes et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day [44.7 mg/day<xref ref-type="table-fn" rid="tfn33-ce-1-103">a</xref>
] (n=117)<break></break>
T 100 mg/day [78.3 mg/day<xref ref-type="table-fn" rid="tfn33-ce-1-103">a</xref>
] (n=125)<break></break>
T 200 mg/day [116.2 mg/day<xref ref-type="table-fn" rid="tfn33-ce-1-103">a</xref>
] (n=112)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: 1%<break></break>
T 50: 5%<break></break>
T 100: 10%<break></break>
T 200: 12%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: increase 0.3%<break></break>
T 50: decrease 2.4%<break></break>
T 100: decrease 3.8%<break></break>
T 200: decrease 3.9%<break></break>
All T <italic>P</italic>
<0.01 vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-ce-1-103">Silberstein et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 2 double-blind single-center RCTs, 8–12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=36)<break></break>
T 200 mg/day (n=34)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: No change<break></break>
T: decrease 5.5 lb<break></break>
<italic>P</italic>
=0.0005 T vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b28-ce-1-103">Edwards et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Multicenter RCT, 7 weeks double-blind followed by 11 weeks open-label</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=115)<break></break>
T 50 mg/day (n=117)<break></break>
T 100 mg/day (n=125)<break></break>
T 200 mg/day (n=112)<xref ref-type="table-fn" rid="tfn34-ce-1-103">b</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: increase 0.3%<break></break>
T 50: decrease 2.4%<break></break>
T 100 or T 200: decrease 3.8%<xref ref-type="table-fn" rid="tfn35-ce-1-103">c</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b63-ce-1-103">Silberstein 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind single-center RCT, 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=37)<break></break>
T 100 mg/day (n=35)<xref ref-type="table-fn" rid="tfn36-ce-1-103">d</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: 0<break></break>
T: 23%</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b55-ce-1-103">Mei et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind, single-center RCT, 8 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=21)<break></break>
T 200 mg/day [125 mg/day<xref ref-type="table-fn" rid="tfn33-ce-1-103">a</xref>
] (n=19)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: 29%<break></break>
T: 53%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: increase 0.55 lb<break></break>
T: decrease 4.88 lb<break></break>
<italic>P</italic>
=0.015 T vs placebo</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b73-ce-1-103">Storey et al. 2001</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Double-blind multicenter RCT, 18 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo (n=143)<break></break>
T 100 mg/day [87.9 mg/day] (n=139)<break></break>
T 200 mg/day [124.2 mg/day] (n=143)<break></break>
Propranolol 160 [129.6 mg/day] mg/day (n=143)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: 1%<break></break>
T 100: 7%<break></break>
T 200: 9%<break></break>
Propranolol: 0%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: increase 0.6%<break></break>
T 100: decrease 2.7% (<italic>P</italic>
≤0.001 vs placebo)<break></break>
T 200: decrease 3.4% (<italic>P</italic>
≤0.001 vs placebo)<break></break>
Propranolol: increase 2.3% (<italic>P</italic>
=0.025 vs placebo)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b25-ce-1-103">Diener et al. 2004</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Pooled analysis of 4 RCTs</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo<break></break>
T 50 mg/day<break></break>
T 100 mg/day<break></break>
T 200 mg/day (n=1580 total)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Placebo: NR<break></break>
T 50: decrease 1.8 kg<break></break>
T 100: decrease 2.5 kg<break></break>
T 200: decrease 2.8 kg<xref ref-type="table-fn" rid="tfn35-ce-1-103">c</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b44-ce-1-103">Lainez et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Open survey, mean treatment duration 7 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">T up to 50 mg/day (n=102)</td>
<td align="left" valign="top" rowspan="1" colspan="1">33%</td>
<td align="left" valign="top" rowspan="1" colspan="1">3–20 kg in 90 days (no mean given)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b40-ce-1-103">Kowacs et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Retrospective case series, mean treatment duration 149 days</td>
<td align="left" valign="top" rowspan="1" colspan="1">T mean dose 208 mg/day (n=74)<break></break>
Topiramate treatment period compared with previous treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">NR</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease 3.1 kg (3.8%)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b81-ce-1-103">Young et al. 2002</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Open-label longitudinal single-center study, 134 patients assessed after 3 months of topiramate treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">T titrated up to 100 mg/day target dose</td>
<td align="left" valign="top" rowspan="1" colspan="1">78%</td>
<td align="left" valign="top" rowspan="1" colspan="1">Decrease 3.44 kg</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b41-ce-1-103">Krymchantowski & Tavares 2004</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn33-ce-1-103"><label>a</label>
<p>Mean dose.</p>
</fn>
<fn id="tfn34-ce-1-103"><label>b</label>
<p>Patient numbers unclear in the original as the numbers given in the figures (given here) do not match the numbers given in the text.</p>
</fn>
<fn id="tfn35-ce-1-103"><label>c</label>
<p>No between-group comparison reported.</p>
</fn>
<fn id="tfn36-ce-1-103"><label>d</label>
<p>Patients who completed the trial.</p>
</fn>
<fn id="tfn37-ce-1-103"><p>ITT, intention-to-treat; NR, not reported; NSD, not statistically significantly different; RCT, randomized controlled trial; T, topiramate.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t10-ce-1-103" position="float"><label>Table 10</label>
<caption><p>Effects of topiramate in refractory and/or transformed migraine (all level 3 evidence)</p>
</caption>
<table frame="box" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Design and patients</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Treatment</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Results</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Reference</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Observational study in patients with >1 migraine/week, who had not responded to or tolerated beta blockers, amitriptyline, flunarizine, and/or valproate (n=115)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Topiramate (most common dose 100 mg/day) for 3 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">56% responded (reduction in migraine frequency >50%)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b58-ce-1-103">Pascual et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Retrospective chart review of patients with transformed migraine (n=96)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Add-on topiramate (mean dose 87.5 mg/day), mean follow-up 8.4 months<xref ref-type="table-fn" rid="tfn38-ce-1-103">a</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Reduction in mean migraine frequency, mean severity, mean headache days/month, mean MIDAS score and rescue medication use vs baseline (<italic>P</italic>
<0.01)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b53-ce-1-103">Mathew et al. 2002</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Retrospective chart review of patients who had not responded to a median of 9 preventive migraine medications (n=69)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Topiramate (median dose 100 mg/day), median follow-up 12 weeks<break></break>
49 of 69 patients took additional preventive therapy</td>
<td align="left" valign="top" rowspan="1" colspan="1">Reduction in mean 28-day frequency of moderate/severe migraines vs baseline (<italic>P</italic>
=0.0004).<break></break>
NSD vs baseline for frequency of mild headaches</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b76-ce-1-103">Von Seggern et al. 2002</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Uncontrolled trial in patients with >3 migraines/month, 80% were taking propranolol and/or flunarizine (n=36)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Add-on topiramate (up to 100 mg/day) for 3 months</td>
<td align="left" valign="top" rowspan="1" colspan="1">Reduction in mean migraine frequency, duration and intensity vs baseline (<italic>P</italic>
<0.001)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b52-ce-1-103">Martinéz et al. 2003</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Uncontrolled trial in patients with high frequency migraine refractory to other prophylactic drugs (n=7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">Topiramate 100 mg/day for 12 weeks maintenance</td>
<td align="left" valign="top" rowspan="1" colspan="1">Reduction in mean number of days with migraine vs baseline (<italic>P</italic>
=0.0036)</td>
<td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b75-ce-1-103">Tonini et al. 2003</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn38-ce-1-103"><label>a</label>
<p>For all patients in the study, including patients with episodic migraine (n=70) and cluster headache (n=12).</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Nadin, Carole" sort="Nadin, Carole" uniqKey="Nadin C" first="Carole" last="Nadin">Carole Nadin</name>
</noCountry>
</tree>
</affiliations>
</record>
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