498 lines
130 KiB
Text
498 lines
130 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-toc">
|
|
<meta name="ncbi_acc" content="NBK591345">
|
|
<meta name="ncbi_domain" content="niceng217er32">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK591345/?report=reader">
|
|
<meta name="ncbi_pagename" content="Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="toc">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="1">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE,NOIMAGEINDEX">
|
|
<meta name="author" content="National Guideline Alliance (UK)">
|
|
<meta name="citation_title" content="Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome">
|
|
<meta name="citation_publisher" content="National Institute for Health and Care Excellence (NICE)">
|
|
<meta name="citation_date" content="2022/04">
|
|
<meta name="citation_author" content="National Guideline Alliance (UK)">
|
|
<meta name="citation_pmid" content="37172081">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK591345/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="National Institute for Health and Care Excellence (NICE)">
|
|
<meta name="DC.Contributor" content="National Guideline Alliance (UK)">
|
|
<meta name="DC.Date" content="2022/04">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK591345/">
|
|
<meta name="og:title" content="Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK591345/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-niceng217er32-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/niceng217er32/toc/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK591345/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8B959C7D6E80C1000000000080006A.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK591345/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-cmap-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK591345/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK591345/&text=Effectiveness%20of%20antiseizure%20therapies%20in%20the%20treatment%20of%20Lennox-Gastaut%20syndrome"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-cmap-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">In Page Navigation</div></div><div class="cnt lol f1"><a href="/books/n/niceercollect/?report=reader">NICE Evidence Reviews Collection</a><a class="current">Title Information</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK591345/?report=classic">Switch to classic view</a><a href="/books/n/niceng217er32/pdf/">PDF (1.0M)</a><a href="/books/n/niceng217er32/toc/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK591345%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8B959C7D6E80C1000000000080006A.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style"><div class="fm-sec bkr_bottom_sep"><div class="bkr_thumb"><a href="https://www.nice.org.uk" title="National Institute for Health and Care Excellence (NICE)" class="img_link icnblk_img" ref="pagearea=logo&targetsite=external&targetcat=link&targettype=publisher"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-niceng217er32-lrg.png" alt="Cover of Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome" /></a></div><div class="bkr_bib"><h1 id="_NBK591345_"><span itemprop="name">Effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome</span></h1><div class="subtitle">Epilepsies in children, young people and adults</div><p><b>Evidence review L</b></p><p><i>NICE Guideline, No. 217</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Alliance (UK)</span>.</p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2022 Apr</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-4513-9</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2022.</div></div><div class="bkr_clear"></div></div><div id="niceng217er32.s1"><h2 id="_niceng217er32_s1_">Evidence review for effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome</h2><div id="niceng217er32.s1.1"><h3>Review question</h3><p>What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</p><div id="niceng217er32.s1.1.1"><h4>Introduction</h4><p>Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy of childhood that typically becomes apparent between 1 and 7 years with a peak at 3 to 5 years of age. In up to 30% of cases Lennox-Gastaut syndrome is preceded by an earlier onset epilepsy syndrome such as West syndrome (infantile spasms). It is characterised by multiple seizure types – typically tonic seizures, atonic seizures and atypical absence seizures. The typical EEG pattern during wakefulness shows slow spike and wave activity, but characteristic fast rhythms may be seen during a sleep recording and may be associated with clinically evident tonic seizures. The syndrome has multiple aetiologies with a causal structural abnormality in up to 70%. Overall the prognosis is poor with continuing seizures and severe learning and behaviour difficulties into adult life. The aim of this review is to identify which antiseizure therapies are the most effective in the treatment of Lennox-Gastaut syndrome.</p></div><div id="niceng217er32.s1.1.2"><h4>Summary of the protocol</h4><p>Please see <a class="figpopup" href="/books/NBK591345/table/niceng217er32.tab1/?report=objectonly" target="object" rid-figpopup="figniceng217er32tab1" rid-ob="figobniceng217er32tab1">Table 1</a> for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab1"><a href="/books/NBK591345/table/niceng217er32.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab1" rid-ob="figobniceng217er32tab1"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab1/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab1/?report=previmg" alt="Table 1. Summary of the protocol (PICO table)." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab1"><a href="/books/NBK591345/table/niceng217er32.tab1/?report=objectonly" target="object" rid-ob="figobniceng217er32tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For further details see the review protocol in <a href="#niceng217er32.appa">appendix A</a>.</p></div><div id="niceng217er32.s1.1.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng217er32.appa">appendix A</a> and the methods document (<a href="/books/NBK591345/bin/niceng217er32_bm1.pdf">supplementary document 1</a>).</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng217er32.s1.1.4"><h4>Clinical evidence</h4><div id="niceng217er32.s1.1.4.1"><h5>Included studies</h5><p>Eight randomised controlled trials (RCTs) and one follow-up study were identified for inclusion in this review (<a class="bibr" href="#niceng217er32.ref1" rid="niceng217er32.ref1">Arzimanoglou 2019</a>, <a class="bibr" href="#niceng217er32.ref3" rid="niceng217er32.ref3">Conry 2009</a>, <a class="bibr" href="#niceng217er32.ref4" rid="niceng217er32.ref4">Dodson 1993</a>, <a class="bibr" href="#niceng217er32.ref5" rid="niceng217er32.ref5">Felbamate study group 1993</a>, <a class="bibr" href="#niceng217er32.ref6" rid="niceng217er32.ref6">Glauser 2008</a>, <a class="bibr" href="#niceng217er32.ref7" rid="niceng217er32.ref7">Motte 1997</a>, <a class="bibr" href="#niceng217er32.ref8" rid="niceng217er32.ref8">Ng 2011</a>, <a class="bibr" href="#niceng217er32.ref9" rid="niceng217er32.ref9">Ohtsuka 2014</a>, <a class="bibr" href="#niceng217er32.ref10" rid="niceng217er32.ref10">Sachdeo 1999</a>). Two of the included articles provided data from the same population, comparing felbamate with placebo: 1 RCT (<a class="bibr" href="#niceng217er32.ref5" rid="niceng217er32.ref5">Felbamate study group 1993</a>) and 1 follow-up study (<a class="bibr" href="#niceng217er32.ref4" rid="niceng217er32.ref4">Dodson 1993</a>).</p><p>One RCT compared add-on rufinamide with any other add-on antiseizure medication (<a class="bibr" href="#niceng217er32.ref1" rid="niceng217er32.ref1">Arzimanoglou 2019</a>); 1 RCT compared add-on low-dose clobazam with add-on high-dose clobazam (<a class="bibr" href="#niceng217er32.ref3" rid="niceng217er32.ref3">Conry 2009</a>); 1 RCT and 1 follow-up study reported results from a study comparing add-on felbamate with placebo (<a class="bibr" href="#niceng217er32.ref5" rid="niceng217er32.ref5">Felbamate study group 1993</a>, <a class="bibr" href="#niceng217er32.ref4" rid="niceng217er32.ref4">Dodson 1993</a>); 2 RCTs compared add-on rufinamide with placebo (<a class="bibr" href="#niceng217er32.ref6" rid="niceng217er32.ref6">Glauser 2008</a>, <a class="bibr" href="#niceng217er32.ref9" rid="niceng217er32.ref9">Ohtsuka 2014</a>); 1 RCT compared add-on lamotrigine with placebo (<a class="bibr" href="#niceng217er32.ref7" rid="niceng217er32.ref7">Motte 1997</a>); 1 RCT compared add-on dose-ranging clobazam with placebo (<a class="bibr" href="#niceng217er32.ref8" rid="niceng217er32.ref8">Ng 2011</a>); and 1 RCT compared add-on topiramate with placebo (<a class="bibr" href="#niceng217er32.ref10" rid="niceng217er32.ref10">Sachdeo 1999</a>).</p><p>The included studies are summarised in <a class="figpopup" href="/books/NBK591345/table/niceng217er32.tab2/?report=objectonly" target="object" rid-figpopup="figniceng217er32tab2" rid-ob="figobniceng217er32tab2">Table 2</a> to <a class="figpopup" href="/books/NBK591345/table/niceng217er32.tab8/?report=objectonly" target="object" rid-figpopup="figniceng217er32tab8" rid-ob="figobniceng217er32tab8">Table 8</a>.</p><p>See the literature search strategy in <a href="#niceng217er32.appb">appendix B</a> and study selection flow chart in <a href="#niceng217er32.appc">appendix C</a>.</p></div><div id="niceng217er32.s1.1.4.2"><h5>Excluded studies</h5><p>Studies not included in this review with reasons for their exclusions are provided in <a href="#niceng217er32.appk">appendix K</a>.</p></div></div><div id="niceng217er32.s1.1.5"><h4>Summary of clinical studies included in the evidence review</h4><p>Summaries of the studies that were included in this review are presented in <a class="figpopup" href="/books/NBK591345/table/niceng217er32.tab2/?report=objectonly" target="object" rid-figpopup="figniceng217er32tab2" rid-ob="figobniceng217er32tab2">Table 2</a> to <a class="figpopup" href="/books/NBK591345/table/niceng217er32.tab8/?report=objectonly" target="object" rid-figpopup="figniceng217er32tab8" rid-ob="figobniceng217er32tab8">Table 8</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab2"><a href="/books/NBK591345/table/niceng217er32.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab2" rid-ob="figobniceng217er32tab2"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab2/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab2/?report=previmg" alt="Table 2. Summary of included studies. Comparison 1: add-on rufinamide versus any other add-on antiseizure medication." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab2"><a href="/books/NBK591345/table/niceng217er32.tab2/?report=objectonly" target="object" rid-ob="figobniceng217er32tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 1: add-on rufinamide versus any other add-on antiseizure medication. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab3"><a href="/books/NBK591345/table/niceng217er32.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab3" rid-ob="figobniceng217er32tab3"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab3/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab3/?report=previmg" alt="Table 3. Summary of included studies. Comparison 2: add-on low-dose clobazam versus add-on high-dose clobazam." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab3"><a href="/books/NBK591345/table/niceng217er32.tab3/?report=objectonly" target="object" rid-ob="figobniceng217er32tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 2: add-on low-dose clobazam versus add-on high-dose clobazam. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab4"><a href="/books/NBK591345/table/niceng217er32.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab4" rid-ob="figobniceng217er32tab4"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab4/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab4/?report=previmg" alt="Table 4. Summary of included studies. Comparison 3: add-on felbamate versus placebo." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab4"><a href="/books/NBK591345/table/niceng217er32.tab4/?report=objectonly" target="object" rid-ob="figobniceng217er32tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 3: add-on felbamate versus placebo. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab5"><a href="/books/NBK591345/table/niceng217er32.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab5" rid-ob="figobniceng217er32tab5"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab5/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab5/?report=previmg" alt="Table 5. Summary of included studies. Comparison 4: add-on rufinamide versus placebo." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab5"><a href="/books/NBK591345/table/niceng217er32.tab5/?report=objectonly" target="object" rid-ob="figobniceng217er32tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 4: add-on rufinamide versus placebo. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab6"><a href="/books/NBK591345/table/niceng217er32.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab6" rid-ob="figobniceng217er32tab6"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab6/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab6/?report=previmg" alt="Table 6. Summary of included studies. Comparison 5: add-on lamotrigine versus placebo." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab6"><a href="/books/NBK591345/table/niceng217er32.tab6/?report=objectonly" target="object" rid-ob="figobniceng217er32tab6">Table 6</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 5: add-on lamotrigine versus placebo. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab7"><a href="/books/NBK591345/table/niceng217er32.tab7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab7" rid-ob="figobniceng217er32tab7"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab7/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab7/?report=previmg" alt="Table 7. Summary of included studies. Comparison 6, 7, and 8: dose-ranging clobazam (add-on) versus placebo." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab7"><a href="/books/NBK591345/table/niceng217er32.tab7/?report=objectonly" target="object" rid-ob="figobniceng217er32tab7">Table 7</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 6, 7, and 8: dose-ranging clobazam (add-on) versus placebo. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32tab8"><a href="/books/NBK591345/table/niceng217er32.tab8/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32tab8" rid-ob="figobniceng217er32tab8"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.tab8/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.tab8/?report=previmg" alt="Table 8. Summary of included studies. Comparison 9: add-on topiramate versus placebo." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.tab8"><a href="/books/NBK591345/table/niceng217er32.tab8/?report=objectonly" target="object" rid-ob="figobniceng217er32tab8">Table 8</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. Comparison 9: add-on topiramate versus placebo. </p></div></div><p>See the full evidence tables in <a href="#niceng217er32.appd">appendix D</a> and forest plots in <a href="#niceng217er32.appe">appendix E</a>.</p></div><div id="niceng217er32.s1.1.6"><h4>Summary of the evidence</h4><p>No evidence regarding monotherapy or first-line therapies were identified in this review. Amongst the second-line interventions identified, add-on lamotrigine, add-on rufinamide, add-on high-dose and medium-dose clobazam, add-on topiramate and add-on felbamate showed important differences with the interventions they were compared with, usually placebo. The majority of the evidence from these studies was very low to moderate quality; most outcomes had very serious imprecision and were at risk of bias due to lack of information regarding randomisation and allocation concealment.</p><p>For instance, add-on lamotrigine was associated with clinically important benefits in relation to reduction in seizure frequency >50%, and reduction in drop attacks when compared to placebo; add-on rufinamide was associated with clinically important benefits in relation to reduction in seizure frequency >50%, improvement in seizure severity, reduction in drop attacks and reduction in tonic seizures when compared to placebo; add-on high-dose and medium-dose clobazam were associated with reduced seizure frequency when compared to lo-dose clobazam. Finally, add-on topiramate was associated with clinically important reductions in seizure frequency >50%, and complete reduction in drop attacks when compared with placebo; and add-on felbamate was associated with clinically important benefis in relation to mean reduction of seizure frequency (all, atonic, generalised tonic-clonic) and quality of life when compared to placebo.</p><p>No clinically important differences were found for add-on rufinamide versus any other add-on antiseizure medication (note that only paediatric patients were included) and add-on low dose clobazam versus placebo.</p><p>No evidence was found for the following antiseizure therapies: carbamazepine, clonazepam, ethosuximide, gabapentin, ketogenic diet, lacosamide, levetiracetam, oxcarbazepine, pregabalin, sodium valproate, tiagabine, vigabatrin and zonisamide.</p></div><div id="niceng217er32.s1.1.7"><h4>Quality assessment of clinical outcomes included in the evidence review</h4><p>See the clinical evidence profiles in <a href="#niceng217er32.appf">appendix F</a>.</p></div><div id="niceng217er32.s1.1.8"><h4>Economic evidence</h4><div id="niceng217er32.s1.1.8.1"><h5>Included studies</h5><p>Two relevant papers were identified in the literature review of published economic evidence on this topic (<a class="bibr" href="#niceng217er32.ref2" rid="niceng217er32.ref2">Benedict 2010</a>; <a class="bibr" href="#niceng217er32.ref11" rid="niceng217er32.ref11">Verdian 2010</a>; see <a href="#niceng217er32.apph">appendix H</a> and <a href="#niceng217er32.appi">appendix I</a> for summary and full evidence tables). Both papers considered the cost effectiveness of rufinamide compared to topiramate and lamotrigine as an adjunctive treatment in children with Lennox-Gastaut syndrome. <a class="bibr" href="#niceng217er32.ref2" rid="niceng217er32.ref2">Benedict 2010</a> also included standard therapy alone as a comparator.</p></div><div id="niceng217er32.s1.1.8.2"><h5>Excluded studies</h5><p>A global search of economic evidence was undertaken for all review questions in this guideline. See <a href="/books/NBK591345/bin/niceng217er32_bm3.pdf">supplementary materia 2</a> for details.</p></div></div><div id="niceng217er32.s1.1.9"><h4>Summary of studies included in the economic evidence review</h4><p><a class="bibr" href="#niceng217er32.ref2" rid="niceng217er32.ref2">Benedict 2010</a> was a cost effectiveness analysis which reported outcomes in terms of cost per 1% increase in successfully treated patients in terms of tonic-atonic (drop attack) frequency and cost per 1% increase in successfully treated patients in terms of total seizure. Success was defined as a greater than 50% reduction in frequency.</p><p><a class="bibr" href="#niceng217er32.ref11" rid="niceng217er32.ref11">Verdian 2010</a> was a cost utility analysis which reported outcomes in terms of incremental cost per QALY. Utility values were estimated using time trade off methodology from 119 members of the UK general population.</p><p>Both studies adopted the perspective of the NHS & PSS. Both studies received funding from the manufacturer of rufinamide.</p></div><div id="niceng217er32.s1.1.10"><h4>Economic model</h4><p>No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.</p></div><div id="niceng217er32.s1.1.11"><h4>Evidence statements</h4><ul><li class="half_rhythm"><div>There was evidence from 1 UK cost effectiveness analysis showing rufinamide cost an extra £62 and £2151 per 1% reduction in drop attacks and total seizures respectively compared to lamotrigine, topiramate andstandard therapy in children with Lennox-Gastaut syndrome. It was deemed partially applicable to the decision problem because whilst it took a UK NHS & PSS perspective it did not report outcomes in terms of quality adjusted life years (QALYs). It was deemed to have potentially serious methodological limitations as there was a lack of transparency around some parameters. It was deemed directly applicable to the decision problem but was deemed to have potentially serious methodological limitations.</div></li><li class="half_rhythm"><div>There was evidence from 1 UK cost utility model comparing rufinamide ith lamotrigine and topiramate in children with Lennox_Gastaut syndrome. The study estimated a cost per QALY for RUF of £20,538 and £154,831 compared to TPM and LTG respectively. There was a 52% and 8% probability that RUF was cost effective at a £20,000 per QALY threshold.</div></li></ul></div><div id="niceng217er32.s1.1.12"><h4>Summary of the economic evidence</h4><p>Two economic evaluations relevant to the decision problem were identified (<a class="bibr" href="#niceng217er32.ref2" rid="niceng217er32.ref2">Benedict 2010</a>, <a class="bibr" href="#niceng217er32.ref11" rid="niceng217er32.ref11">Verdian 2010</a>).</p><p><a class="bibr" href="#niceng217er32.ref2" rid="niceng217er32.ref2">Benedict 2010</a> was a patient simulation model comparing rufinamide (RUF) to lamotrigine (LTG), topiramate (TPM) and standard therapy in people with Lennox-Gastaut syndrome (LGS). It was deemed partially applicable to the decision problem because whilst it took a UK NHS & PSS perspective it did not report outcomes in terms of quality adjusted life years (QALYs). It was deemed to have potentially serious methodological limitations as it was funded by the manufacturer of RUF and there was a lack of transparency around some parameters. The study presented 2 analyses one considering reduction in drop attacks and the other reduction in total seizures. RUF was associated with a £62 cost per 1% reduction in drop attacks (compared to TPM) and £2151 per reduction in total seizures (compared to LTG). There was an 80% probability that RUF was the optimal treatment when willingness to pay for a 1% reduction in drop attacks and total seizures was £250 and £900 respectively.</p><p><a class="bibr" href="#niceng217er32.ref11" rid="niceng217er32.ref11">Verdian 2010</a> was a Markov model comparing RUF to LMG and TPM as an adjunctive treatment in children with LGS. It was deemed directly applicable to the decision problem as it took a NHS & PSS perspective and reported outcomes in terms of cost per QALY. It was deemed to have potentially serious methodological limitations due to being funded by the manufacturer of RUF and lack of transparency around estimates of key parameters. The study estimated a cost per QALY for RUF of £20,538 and £154,831 compared to TPM and LTG respectively. There was a 52% and 8% probability that RUF was cost effective at a £20,000 per QALY threshold.See <a href="#niceng217er32.apph">appendix H</a> and <a href="#niceng217er32.appi">appendix I</a> for summary and full evidence tables.</p></div><div id="niceng217er32.s1.1.13"><h4>The committee’s discussion of the evidence</h4><div id="niceng217er32.s1.1.13.1"><h5>Interpreting the evidence</h5><div id="niceng217er32.s1.1.13.1.1"><h5>The outcomes that matter most</h5><p>The main objective of treatment for children with Lennox-Gastaut syndrome is to control seizures as much as possible whilst minimising the risk of adverse events. The committee therefore agreed that reduction in seizure frequency >50%, time to withdrawal of treatment or change of medication, and adverse events (as assessed by trial-defined adverse and serious adverse events and mortality) should be designated as critical outcomes for this review. As ‘drop attacks’ (also described as tonic, atonic, or tonic-clonic attacks) are a key feature of Lennox-Gastaut syndrome, reduction in drop attacks specifically was also included as a critical outcome in this review.</p><p>Balancing the need to control seizures with the need to maintain (or improve) quality of life is a key issue in the treatment of children with Lennox Gastaut syndrome and the committee therefore agreed that overall quality of life should be included as an important outcome. The committee also agreed to include neurodevelopment outcomes and social functioning changes as important outcomes as better seizure control is expected to lead to improvements in a child’s developmental abilities.</p></div><div id="niceng217er32.s1.1.13.1.2"><h5>The quality of the evidence</h5><p>The quality of the evidence for this review was assessed using GRADE methodology. The majority of outcomes were considered very low, low or moderate quality evidence, indicating high uncertainly in the reliability of the data. This was with the exception of some of the outcomes reported by <a class="bibr" href="#niceng217er32.ref6" rid="niceng217er32.ref6">Glauser 2008</a>, <a class="bibr" href="#niceng217er32.ref8" rid="niceng217er32.ref8">Ng 2011</a> and <a class="bibr" href="#niceng217er32.ref9" rid="niceng217er32.ref9">Ohtsuka 2014</a>, which were considered high quality.</p><p>Data was generally downgraded due to risk of bias, with limited information provided regarding randomisation and allocation concealment. Data was also downgraded due to imprecision. The included studies only included a small number of participants; therefore, overall the data should be regarded with some caution.</p></div><div id="niceng217er32.s1.1.13.1.3"><h5>Benefits and harms</h5><p>The committee considered the evidence included within this evidence review and used the evidence and their expertise to make recommendations.</p><p>Lennox-Gastaut syndrome is a severe developmental and epileptic encephalopathy that is characterised by different types of seizures, intellectual disability and abnormal EEG features. Diagnosis is often difficult to establish because the seizure types and EEG features it presents with are not specifically indicative of this syndrome, and because these tend to evolve over time. The committee highlighted that treatment is also likely to have been initiated before the diagnosis is established, often because it is challenging to distinguish this epilepsy syndrome from others, particularly in the early stages of the presentation. For these reasons, and based on their experience and expertise, the committee agreed that the involvement of an adult or paediatric neurologist is needed to guide the care of people with Lennox-Gastaut. This is standard current practice, therefore the committee did not think this recommendation would lead to increased costs or resource use.</p><p>The committee agreed that, prior to starting antiseizure therapy there should be a discussion with the person, their family and carers, if appropriate, about an individualised antiseizure therapy strategy according to their syndrome type, treatment goals and the preferences of the person and their family or carers as appropriate. Treatment plans should be regularly reassessed, and its agreement should include a transparent explanation of the epilepsy type, severity and duration of adverse effects that the person with epilepsy may experience and how should these be managed. The person, their family and carers, should also be made aware that they should be taking the least amount of medicines as possible to be effective due to the side effects of being on numerous medications.</p><p>No evidence was found assessing the effectiveness of monotherapy or first-line therapy, so the expert opinion of the committee was that sodium valproate should be the first-line medication in people with Lennox-Gastaut syndrome because it is effectively used in clinical practice for generalised seizures, including Lennox-Gastaut syndrome, and because the severity of the syndrome and the lack of evidence for alternative first-line options. The committee acknowledged the risks associated with sodium valproate if prescribed to women and girls who are able to have children, yet agreed that it should be considered as first-line treatment as approximately two thirds of children outgrow this syndrome and its neurodevelopmental consequences mean that pregnancy is unusual. However the committee agreed that, for women and girls who are able to have children, sodium valproate should only be prescribed after a full and clear discussion with them or their families/carers, as appropriate, ensuring they understand all the potential risks and benefits. If sodium valproate is prescribed to women and girls able to have children, clinicians must follow MHRA guidance, which includes ensuring the continuous use of highly effective contraception and the enrolment of the girl or woman in a <a href="https://www.gov.uk/drug-safety-update/valproate-pregnancy-prevention-programme-actions-required-now-from-gps-specialists-and-dispensers" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">pregnancy prevention programme</a>, if appropriate.</p><p>Based on the available evidence, which showed that, when used as an add-on therapy, lamotrigine reduced seizure frequency, the committee agreed to recommend that lamotrigine should be used as an add-on or alternative therapy if sodium valproate is unsuccessful. The committee agreed that it was appropriate to extrapolate from the add-on evidence on lamotrigine as it is commonly used in clinical practice as monotherapy in Lennox-Gastaut syndrome.</p><p>The evidence suggested that lamotrigine was as effective as clobazam when compared to placebo, however the committee recommended lamotrigine as second-line therapy in preference to clobazam because, according to their experience, it is better tolerated. The committee acknowledged that, due to the extended time required to titrate lamotrigine safely, clobazam is sometimes used in the short term to ameliorate seizures involving injuries. Once lamotrigine has reached adequate treatment doses, the decision to wean clobazam can be made on an individual basis. Clobazam is not licenced for children under 6 years old in the UK, but it can be used on a named-patient basis.</p><p>The evidence suggested that clobazam, rufinamide and topiramate reduce seizure frequency and drop-attacks, therefore the committee recommended these if first- and second-line therapy were unsuccessful or if seizures continue. One of the studies assessing the effectiveness of clobazam conducted analysis by low-, medium- and high-dose, however the committee did not think that it was appropriate to recommend a specific dose of clobazam as this is decided on an individual basis. Furthermore, according to their clinical experience, high doses of clobazam can worsen tonic seizures, although this is rare.</p><p>Although there was no evidence assessing the effectiveness of clobazam, rufinamide and topiramate as a monotherapy, the committee agreed that it was appropriate to extrapolate from the add-on evidence as these ASMs are commonly used in clinical practice for tonic or atonic seizures/drop attacks. The recommendations regarding cannabidiol were adopted from the <a href="https://www.nice.org.uk/guidance/ta614" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE technology appraisal guidance on cannabidiol with clobazam</a> for treating seizures associated with Lennox-Gastaut syndrome.</p><p>The committee emphasised that, monotherapy should be used in the first instance. When starting alternative antiseizure medications, the dose of the new antiseizure medication should be slowly increased, whilst the existing antiseizure medication is tapered off. The committee warned about the potential sedative effects of cannabidiol, clobazam, rufinamide and topiramate. They agreed that these medications should be carefully titrated, in line with the BNF guidance, adverse events monitored, and there should be a frequent treatment review.</p><p>The committee noted that ketogenic diets are successfully used in clinical practice in cases of Lennox-Gastaut syndrome difficult to treat and recommended these as a fourth-line treatment based on their expert opinion. The committee emphasised that these should only be prescribed under the guidance or supervision of a neurologist with expertise in epilepsy as these are calculated individually, and the person’s weight and ketone levels need to be monitored.</p><p>The evidence supported the committee’s experience that felbamate reduced seizure frequency. The committee emphasised that felbamate should only be used in severe drug-resistant cases and should only be considered under the supervision of an epilepsy specialist. This is due to the monitoring required for haematological and hepatic adverse events associated with felbamate, and because it is not licenced for use in the UK.</p><p>Although no evidence was identified which reported on any of the other ASMs included in the protocol for this review, the committee agreed that, whilst these may benefit some patients, clinical experience also suggests that they may exacerbate seizures. Therefore, they agreed to draft a recommendation stating this.</p><p>In the absence of evidence for monotherapy or first-line therapy, the committee agreed to make a recommendation for future research (see <a href="#niceng217er32.appl">Appendix L</a>).</p></div><div id="niceng217er32.s1.1.13.1.4"><h5>Cost effectiveness and resource use</h5><p>The committee considered 2 previously published economic evaluations which considered rufinamide compared to lamotrigine and topiramate. The committee highlighted limitations with the evidence which prevented them making strong recommendations based upon it. Most significantly that both studies were funded by the manufacturer of rufinamide and the lack of transparency around key parameters. Both studies took a NHS & PSS perspective. One study also did not report outcomes in terms of cost per QALY.</p><p>The committee also highlighted the age of the studies (>10 years) and that since these analyses were completed all drugs considered are now off patent and relatively inexpensive. It was therefore considered that the most effective treatment would also be the most cost effective. Given this and the identified weaknesses in the included economic evaluations recommendations were made in line with the clinical evidence.</p><p>The recommendations made for this review question are unlikely to change current practice and therefore no resource impact is anticipated.</p></div><div id="niceng217er32.s1.1.13.1.5"><h5>Other factors the committee took into account</h5><p>In line with the MHRA, the committee emphasised that long-term treatment with sodium valproate can cause decreased bone mineral density and increased risk of osteomalacia. The committee noted that appropriate supplementation should be considered for those at risk.</p></div></div></div><div id="niceng217er32.s1.1.14"><h4>Recommendations supported by this evidence review</h4><p>This evidence review supports recommendations section 6.2.1-6.2.9 and the research recommendation on complex epilepsy syndromes.</p></div></div><div id="niceng217er32.rl.r1"><h3>References</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref1"><p id="p-247">
|
|
<strong>Arzimanoglou 2019</strong>
|
|
</p>Arzimanoglou
|
|
A, Ferreira
|
|
J, Satlin
|
|
A, Olhaye
|
|
O, Kumar
|
|
D, Dhadda
|
|
S, Bibbiani
|
|
F. Evaluation of long-term safety, tolerability, and behavioral outcomes with adjunctive rufinamide in pediatric patients (≥ 1 to< 4 years old) with Lennox-Gastaut syndrome: Final results from randomized study 303. European Journal of Paediatric Neurology. 2019
|
|
Jan
|
|
1;23(1): 126–35. [<a href="https://pubmed.ncbi.nlm.nih.gov/30309816" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30309816</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref2"><p id="p-248">
|
|
<strong>Benedict 2010</strong>
|
|
</p>Benedict
|
|
A, Verdian
|
|
L, Maclaine
|
|
G. The cost-effectiveness of rufinamide in the treatment of Lennox-Gastaut Syndrome in the UK. Pharmacoeconomics. 2010; 28(3): 185–199. [<a href="https://pubmed.ncbi.nlm.nih.gov/20151724" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20151724</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref3"><p id="p-249">
|
|
<strong>Conry 2009</strong>
|
|
</p>Conry
|
|
JA, Ng
|
|
YT, Paolicchi
|
|
JM, Kernitsky
|
|
L, Mitchell
|
|
WG, Ritter
|
|
FJ, Collins
|
|
SD, Tracy
|
|
K, Kormany
|
|
WN, Abdulnabi
|
|
R, Riley
|
|
B. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009
|
|
May;50(5):1158–66. [<a href="https://pubmed.ncbi.nlm.nih.gov/19170737" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19170737</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref4"><p id="p-250">
|
|
<strong>Dodson 1993</strong>
|
|
</p>Dodson
|
|
WE. Felbamate in the treatment of Lennox-Gastaut syndrome: results of a 12-month open-label study following a randomized clinical trial. Epilepsia. 1993
|
|
Dec;34:S18–24. [<a href="https://pubmed.ncbi.nlm.nih.gov/8243374" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8243374</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref5"><p id="p-251">
|
|
<strong>Felbamate study group 1993</strong>
|
|
</p>Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). New England Journal of Medicine. 1993
|
|
Jan
|
|
7;328(1):29–33. [<a href="https://pubmed.ncbi.nlm.nih.gov/8347179" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8347179</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref6"><p id="p-252">
|
|
<strong>Glauser 2008</strong>
|
|
</p>Glauser
|
|
T, Kluger
|
|
G, Sachdeo
|
|
R, Krauss
|
|
G, Perdomo
|
|
C, Arroyo
|
|
S. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. 2008
|
|
May
|
|
20;70(21):1950–8. [<a href="https://pubmed.ncbi.nlm.nih.gov/18401024" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18401024</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref7"><p id="p-253">
|
|
<strong>Motte 1997</strong>
|
|
</p>Motte
|
|
J, Trevathan
|
|
E, Arvidsson
|
|
JF, Barrera
|
|
MN, Mullens
|
|
EL, Manasco
|
|
P, Lamictal LennoxGastaut Study Group. Lamotrigine for generalized seizures associated with the LennoxGastaut syndrome. New England Journal of Medicine. 1997
|
|
Dec
|
|
18;337(25):1807–12. [<a href="https://pubmed.ncbi.nlm.nih.gov/9400037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9400037</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref8"><p id="p-254">
|
|
<strong>Ng 2011</strong>
|
|
</p>Ng
|
|
YT, Conry
|
|
JA, Drummond
|
|
R, Stolle
|
|
J, Weinberg
|
|
MA. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011
|
|
Oct
|
|
11;77(15): 1473–81. [<a href="https://pubmed.ncbi.nlm.nih.gov/21956725" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21956725</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref9"><p id="p-255">
|
|
<strong>Ohtsuka 2014</strong>
|
|
</p>Ohtsuka
|
|
Y, Yoshinaga
|
|
H, Shirasaka
|
|
Y, Takayama
|
|
R, Takano
|
|
H, lyoda
|
|
K. Rufinamide as an adjunctive therapy for Lennox-Gastaut syndrome: a randomized double-blind placebocontrolled trial in Japan. Epilepsy research. 2014
|
|
Nov
|
|
1; 108(9): 1627–36. [<a href="https://pubmed.ncbi.nlm.nih.gov/25219353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25219353</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref10"><p id="p-256">
|
|
<strong>Sachdeo 1999</strong>
|
|
</p>Sachdeo
|
|
RC, Glauser
|
|
TA, Ritter
|
|
FO, Reife
|
|
R, Lim
|
|
P, Pledger
|
|
G, Topiramate YL Study Group. A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome. Neurology. 1999
|
|
Jun
|
|
1;52(9):1882–. [<a href="https://pubmed.ncbi.nlm.nih.gov/10371538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10371538</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng217er32.ref11"><p id="p-257">
|
|
<strong>Verdian 2010</strong>
|
|
</p>Verdian
|
|
L, Yunni
|
|
Y. Cost-utility analysis of rufinamide versus topiramate and lamotrigine for the treatment of children with Lennox-Gastaut Syndrome in the United Kingdom. Seizure. 2010; 19(1):1–11. [<a href="https://pubmed.ncbi.nlm.nih.gov/19942457" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19942457</span></a>]</div></p></li></ul></div></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng217er32.appa"><h3>Appendix A. Review protocols</h3><div id="niceng217er32.appa.s1"><h4>Review protocol for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appa.et1"><a href="/books/NBK591345/bin/niceng217er32-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (229K)</span></p></div></div><div id="niceng217er32.appb"><h3>Appendix B. Literature search strategies</h3><div id="niceng217er32.appb.s1"><h4>Literature search strategies for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appb.et1"><a href="/books/NBK591345/bin/niceng217er32-appb-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (216K)</span></p></div></div><div id="niceng217er32.appc"><h3>Appendix C. Clinical evidence study selection</h3><div id="niceng217er32.appc.s1"><h4>Clinical study selection for: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appc.et1"><a href="/books/NBK591345/bin/niceng217er32-appc-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (118K)</span></p></div></div><div id="niceng217er32.appd"><h3>Appendix D. Clinical evidence tables</h3><div id="niceng217er32.appd.s1"><h4>Clinical evidence tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appd.et1"><a href="/books/NBK591345/bin/niceng217er32-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (344K)</span></p></div></div><div id="niceng217er32.appe"><h3>Appendix E. Forest plots</h3><div id="niceng217er32.appe.s1"><h4>Forest plots for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appe.et1"><a href="/books/NBK591345/bin/niceng217er32-appe-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (136K)</span></p></div></div><div id="niceng217er32.appf"><h3>Appendix F. GRADE tables</h3><div id="niceng217er32.appf.s1"><h4>GRADE tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appf.et1"><a href="/books/NBK591345/bin/niceng217er32-appf-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (375K)</span></p></div></div><div id="niceng217er32.appg"><h3>Appendix G. Economic evidence study selection</h3><div id="niceng217er32.appg.s1"><h4>Economic evidence study selection for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p>A global search of economic evidence was undertaken for all review questions in this guideline. See <a href="/books/NBK591345/bin/niceng217er32_bm3.pdf">Supplement 2</a> for further information</p></div></div><div id="niceng217er32.apph"><h3>Appendix H. Economic evidence tables</h3><div id="niceng217er32.apph.s1"><h4>Economic evidence tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.apph.et1"><a href="/books/NBK591345/bin/niceng217er32-apph-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (186K)</span></p></div></div><div id="niceng217er32.appi"><h3>Appendix I. Economic evidence profiles</h3><div id="niceng217er32.appi.s1"><h4>Economic evidence profiles for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p id="niceng217er32.appi.et1"><a href="/books/NBK591345/bin/niceng217er32-appi-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (168K)</span></p></div></div><div id="niceng217er32.appj"><h3>Appendix J. Economic analysis</h3><div id="niceng217er32.appj.s1"><h4>Economic evidence analysis for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><p>No economic analysis was conducted for this review question.</p></div></div><div id="niceng217er32.appk"><h3>Appendix K. Excluded studies</h3><div id="niceng217er32.appk.s1"><h4>Excluded clinical and economic studies for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><div id="niceng217er32.appk.s1.1"><h5>Clinical studies</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng217er32appktab1"><a href="/books/NBK591345/table/niceng217er32.appk.tab1/?report=objectonly" target="object" title="Table 22" class="img_link icnblk_img figpopup" rid-figpopup="figniceng217er32appktab1" rid-ob="figobniceng217er32appktab1"><img class="small-thumb" src="/books/NBK591345/table/niceng217er32.appk.tab1/?report=thumb" src-large="/books/NBK591345/table/niceng217er32.appk.tab1/?report=previmg" alt="Table 22. Excluded studies and reasons for their exclusion." /></a><div class="icnblk_cntnt"><h4 id="niceng217er32.appk.tab1"><a href="/books/NBK591345/table/niceng217er32.appk.tab1/?report=objectonly" target="object" rid-ob="figobniceng217er32appktab1">Table 22</a></h4><p class="float-caption no_bottom_margin">Excluded studies and reasons for their exclusion. </p></div></div></div><div id="niceng217er32.appk.s1.2"><h5>Economic studies</h5><p>A global search of economic evidence was undertaken for all review questions in this guideline. See <a href="/books/NBK591345/bin/niceng217er32_bm3.pdf">Supplement 2</a> for further information</p></div></div></div><div id="niceng217er32.appl"><h3>Appendix L. Research recommendations</h3><div id="niceng217er32.appl.s1"><h4>Research recommendations for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of seizures in Lennox-Gastaut syndrome?</h4><div id="niceng217er32.appl.s1.1"><h5>Research question</h5><p>What antiseizure therapies (alternative or add-on) are effective in the treatment of complex epilepsy syndromes (that is, Dravet syndrome, Lennox-Gastaut syndrome, infantile spasms syndrome and myoclonic atonic epilepsy [Doose syndrome]) when first-line therapy is unsuccessful or not tolerated?</p></div><div id="niceng217er32.appl.s1.2"><h5>Why this is important</h5><p>There is paucity of evidence from RCTs to support evidence-based treatment decisions in complex epilepsy syndromes when first-line therapy is not successful or not tolerated. These complex epilepsy syndromes are considerered developmental and epileptic encephalopathies due to the negative effects on cognition and behaviour. Seizures are frequently drug-resistant and, in some cases, these syndromes can have long-lasting effects on cognition. Research is needed to identify the safety and effectiveness of second-line antiseizure therapies in Dravet syndrome, Lennox-Gastaut syndrome, infantile spasms syndrome and myoclonic atonic epilepsy (Doose syndrome).</p><p id="niceng217er32.appl.et1"><a href="/books/NBK591345/bin/niceng217er32-appl-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (193K)</span></p></div></div></div></div></div><div class="fm-sec"><div><p>Final version</p></div><div><p>Evidence reviews underpinning recommendation section 6.2.1-6.2.9 in NICE guideline</p><p>These evidence reviews were developed by the National Guideline Alliance which is part of the Royal College of Obstetricians and Gynaecologists</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2022.</div><div class="small"><span class="label">Bookshelf ID: NBK591345</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/37172081" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">37172081</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng217er32tab1"><div id="niceng217er32.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab1_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_niceng217er32.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_niceng217er32.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Children, young people and adults with confirmed Lennox-Gastaut syndrome</div></li></ul>
|
|
</td></tr><tr><th id="hd_b_niceng217er32.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_niceng217er32.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The following anti-epileptic therapies and their combinations will be considered:<ul><li class="half_rhythm"><div>Carbamazepine</div></li><li class="half_rhythm"><div>Clobazam</div></li><li class="half_rhythm"><div>Clonazepam</div></li><li class="half_rhythm"><div>Ethosuximide</div></li><li class="half_rhythm"><div>Felbamate</div></li><li class="half_rhythm"><div>Gabapentin</div></li><li class="half_rhythm"><div>Ketogenic diet (included as this is an accepted first or second line treatment for this syndrome)</div></li><li class="half_rhythm"><div>Lacosamide</div></li><li class="half_rhythm"><div>Lamotrigine</div></li><li class="half_rhythm"><div>Levetiracetam</div></li><li class="half_rhythm"><div>Oxcarbazepine</div></li><li class="half_rhythm"><div>Pregabalin</div></li><li class="half_rhythm"><div>Rufinamide</div></li><li class="half_rhythm"><div>Sodium valproate</div></li><li class="half_rhythm"><div>Tiagabine</div></li><li class="half_rhythm"><div>Topiramate</div></li><li class="half_rhythm"><div>Vigabatrin</div></li><li class="half_rhythm"><div>Zonisamide</div></li></ul></td></tr><tr><th id="hd_b_niceng217er32.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_niceng217er32.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>No treatment/placebo</div></li><li class="half_rhythm"><div>Comparison between the listed interventions (monotherapy or add-on therapy)</div></li><li class="half_rhythm"><div>Different doses of the listed interventions</div></li></ul>
|
|
</td></tr><tr><th id="hd_b_niceng217er32.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_niceng217er32.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>Critical</b>
|
|
<ul><li class="half_rhythm"><div>Reduction in seizure frequency >50%</div></li><li class="half_rhythm"><div>Reduction in drop attacks (may also be described as tonic, atonic, or tonic-clonic attacks)</div></li><li class="half_rhythm"><div>Time to withdrawal of treatment or change of medication (for example, because of uncontrollable seizures)</div></li><li class="half_rhythm"><div>Adverse events, as assessed by:<ul class="circle"><li class="half_rhythm"><div>% of patients with reported side effects (trial defined adverse and serious adverse events)</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects (dichotomous outcome only)</div></li><li class="half_rhythm"><div>Mortality</div></li></ul></div></li></ul>
|
|
</p>
|
|
<p>
|
|
<b>Important</b>
|
|
<ul><li class="half_rhythm"><div>Neurodevelopment outcomes, as assessed by validated developmental/IQ tools, for example the VABS (Vineland Adaptive Behaviour Scale)</div></li><li class="half_rhythm"><div>Social functioning changes (behaviour reported by parents/caregivers/school or validated tools)</div></li><li class="half_rhythm"><div>Overall quality of life (reported by caregiver/the individual with Lennox-Gastaut syndrome). Only validated scales will be included</div></li></ul>
|
|
</p>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">IQ: Intelligence quotient; VABS: Vineland adaptive behaviour scale</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab2"><div id="niceng217er32.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of included studies. Comparison 1: add-on rufinamide versus any other add-on antiseizure medication</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref1" rid="niceng217er32.ref1">Arzimanoglou 2019</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>Canada, USA, France, Greece, Italy, Poland</p>
|
|
</td><td headers="hd_h_niceng217er32.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N= 37 infants with LGS with inadequate responses to treatment with other ASMs (1-3 ASMs)</p>
|
|
<p>Age, months, mean (SD):</p>
|
|
<p>Intervention group = 28.3 (10)</p>
|
|
<p>Control group = 28.9 (9.9)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on rufinamide</u>
|
|
</p>
|
|
<p>n=25</p>
|
|
<p>Target maintenance 45mg/kg/day with existing regimen of 1 to 3 ASM</p>
|
|
</td><td headers="hd_h_niceng217er32.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Any other add-on antiseizure medication</u>
|
|
</p>
|
|
<p>n=12</p>
|
|
<p>In combination with existing regimen of 1 to 3 ASMs</p>
|
|
</td><td headers="hd_h_niceng217er32.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Time to withdrawal of treatment due to adverse events or lack of seizure efficacy</div></li><li class="half_rhythm"><div>% of patients with reported serious side effects</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>Social functioning changes: difference in total problems scores</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASMs: antiseizure medications; Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab3"><div id="niceng217er32.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Summary of included studies. Comparison 2: add-on low-dose clobazam versus add-on high-dose clobazam</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref3" rid="niceng217er32.ref3">Conry 2009</a>
|
|
</p>
|
|
<p>Phase II RCT</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng217er32.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=68 people with LGS</p>
|
|
<p>Age, years, median (range): 7.4 (2 to 26)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on low-dose clobazam</u>
|
|
</p>
|
|
<p>n=32</p>
|
|
<p>Target dose 0.25 mg/kg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on high-dose clobazam</u>
|
|
</p>
|
|
<p>n=36</p>
|
|
<p>Target dose 1.0mg/kg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in seizure frequency >50%</div></li><li class="half_rhythm"><div>Reduction in drop attacks</div></li><li class="half_rhythm"><div>% of patients with reported severe side effects</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>Social functioning changes: % of patients considered to be “improved” or “very much improved” (patient and carer global evaluations)</div></li><li class="half_rhythm"><div>Social functioning changes: % of patients considered to be “improved” or “very much improved” (investigator evaluation)</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab4"><div id="niceng217er32.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Summary of included studies. Comparison 3: add-on felbamate versus placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref5" rid="niceng217er32.ref5">Felbamate study group 1993</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng217er32.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=73 people with LGS</p>
|
|
<p>Age, years, mean (range):</p>
|
|
<p>Intervention group = 12 (4 to 24)</p>
|
|
<p>Control group = 14 (4 to 36)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on felbamate</u>
|
|
</p>
|
|
<p>n=37</p>
|
|
<p>Maximum dose 45mg/kg/day or 3600mg/day, whichever was less</p>
|
|
</td><td headers="hd_h_niceng217er32.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=36</p>
|
|
</td><td headers="hd_h_niceng217er32.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Complete cessation of all seizures<sup>¥</sup></div></li><li class="half_rhythm"><div>Complete cessation of atonic seizures</div></li><li class="half_rhythm"><div>Complete cessation of generalised tonic-clonic seizures</div></li><li class="half_rhythm"><div>Mean change in frequency of all seizures<sup>¥</sup></div></li><li class="half_rhythm"><div>Mean change in frequency of atonic seizures</div></li><li class="half_rhythm"><div>Mean change in frequency of generalised tonic-clonic seizures</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>Mortality</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_niceng217er32.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref4" rid="niceng217er32.ref4">Dodson 1993</a>
|
|
</p>
|
|
<p>Follow-up of <a class="bibr" href="#niceng217er32.ref5" rid="niceng217er32.ref5">Felbamate study group 1993</a> (RCT)</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng217er32.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As above</td><td headers="hd_h_niceng217er32.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As above</td><td headers="hd_h_niceng217er32.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As above</td><td headers="hd_h_niceng217er32.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Global outcome variable (proxy outcome for quality of life)</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>¥</dt><dd><div id="niceng217er32.tab4_1"><p class="no_margin">All seizures: atonic, tonic, generalised tonic-clonic, atypical absence, and complex partial</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab5"><div id="niceng217er32.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">Summary of included studies. Comparison 4: add-on rufinamide versus placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref6" rid="niceng217er32.ref6">Glauser 2008</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>Belgium, Brazil, Germany, Hungary, Italy, Norway, Poland, Spain, and US</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=138 people with LGS</p>
|
|
<p>Age, years, median (range):</p>
|
|
<p>Intervention group = 13 (4 to 35)</p>
|
|
<p>Control group = 10.5 (4 to 37)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on rufinamide</u>
|
|
</p>
|
|
<p>n=74</p>
|
|
<p>Maximum dose 45mg/kg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=64</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in total seizure frequency >50%</div></li><li class="half_rhythm"><div>Improvement in seizure severity</div></li><li class="half_rhythm"><div>Reduction in drop attacks</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>% of patients with reported serious side effects</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_niceng217er32.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref9" rid="niceng217er32.ref9">Ohtsuka 2014</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>Japan</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=59 people with LGS</p>
|
|
<p>Age, years, mean (SD):</p>
|
|
<p>Intervention group = 16 (7.1)</p>
|
|
<p>Control group = 13.9 (6.1)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on rufinamide</u>
|
|
</p>
|
|
<p>n=29</p>
|
|
<p>Maximum dose was 3200mg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=30</p>
|
|
</td><td headers="hd_h_niceng217er32.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in seizure frequency > 50%</div></li><li class="half_rhythm"><div>Reduction in tonic seizures</div></li><li class="half_rhythm"><div>Reduction in atonic seizures</div></li><li class="half_rhythm"><div>Reduction in tonic-clonic seizures</div></li><li class="half_rhythm"><div>% of patients with a dose reduction due to safety concerns</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>% of patients with reported serious side effects</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab6"><div id="niceng217er32.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">Summary of included studies. Comparison 5: add-on lamotrigine versus placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab6_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref7" rid="niceng217er32.ref7">Motte 1997</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>France, US, Spain, UK</p>
|
|
</td><td headers="hd_h_niceng217er32.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N= 169 people with LGS</p>
|
|
<p>Age, years, mean (SD):</p>
|
|
<p>Intervention group = 9.6 (5.2)</p>
|
|
<p>Control group = 10.9 (5.9)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on lamotrigine</u>
|
|
</p>
|
|
<p>n=79</p>
|
|
<p>Maximum dose was 400mg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=90</p>
|
|
</td><td headers="hd_h_niceng217er32.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in seizure frequency > 50%</div></li><li class="half_rhythm"><div>Reduction in drop attacks</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab7"><div id="niceng217er32.tab7" class="table"><h3><span class="label">Table 7</span><span class="title">Summary of included studies. Comparison 6, 7, and 8: dose-ranging clobazam (add-on) versus placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab7_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref8" rid="niceng217er32.ref8">Ng 2011</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>US, Europe, India and Australia</p>
|
|
</td><td headers="hd_h_niceng217er32.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=238 people with LGS</p>
|
|
<p>Age, years, mean (SD):</p>
|
|
<p>placebo group = 13 (9.2)</p>
|
|
<p>low-dose group = 10.9 (7.2)</p>
|
|
<p>medium-dose group = 14.1 (10.4)</p>
|
|
<p>high-dose group = 11.7 (8.5)</p>
|
|
</td><td headers="hd_h_niceng217er32.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on dose-ranging clobazam</u>
|
|
</p>
|
|
<p>n=58</p>
|
|
<p>randomised to clobazam 0.25 mg/kg/day [low dose];</p>
|
|
<p>n=62 randomised to clobazam 0.5 mg/kg/day [medium dose]; and</p>
|
|
<p>n=59 randomised to clobazam 1 mg/kg/day [high dose]</p>
|
|
</td><td headers="hd_h_niceng217er32.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=59</p>
|
|
</td><td headers="hd_h_niceng217er32.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in seizure frequency > 50%</div></li><li class="half_rhythm"><div>Complete reduction in drop attacks</div></li><li class="half_rhythm"><div>% of patients with a change in medication dose</div></li><li class="half_rhythm"><div>% of patients with reported serious side effects</div></li><li class="half_rhythm"><div>Mortality</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32tab8"><div id="niceng217er32.tab8" class="table"><h3><span class="label">Table 8</span><span class="title">Summary of included studies. Comparison 9: add-on topiramate versus placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.tab8_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng217er32.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng217er32.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng217er32.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><th id="hd_h_niceng217er32.tab8_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng217er32.ref10" rid="niceng217er32.ref10">Sachdeo 1999</a>
|
|
</p>
|
|
<p>RCT</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng217er32.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=98 people with LGS</p>
|
|
<p>Age, years, mean (SD) in the intervention group 11.2 (6.2) and in the control group 11.2 (7.70</p>
|
|
</td><td headers="hd_h_niceng217er32.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Add-on topiramate</u>
|
|
</p>
|
|
<p>n=48</p>
|
|
<p>Target dose was 6mg/kg/day</p>
|
|
</td><td headers="hd_h_niceng217er32.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<u>Placebo</u>
|
|
</p>
|
|
<p>n=50</p>
|
|
</td><td headers="hd_h_niceng217er32.tab8_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Reduction in major seizure frequency (drop attacks and tonic-clonic seizures) >50%</div></li><li class="half_rhythm"><div>Complete cessation of drop attacks</div></li><li class="half_rhythm"><div>% of patients with reported severe adverse side effects</div></li><li class="half_rhythm"><div>Treatment cessation due to adverse medication effects</div></li><li class="half_rhythm"><div>% of patients with dose reduction or temporary discontinuation of treatment</div></li></ul>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Kg: kilogram; LGS: Lennox-Gastaut syndrome; mg: milligram; RCT: randomised controlled trial; SD: standard deviation</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng217er32appktab1"><div id="niceng217er32.appk.tab1" class="table"><h3><span class="label">Table 22</span><span class="title">Excluded studies and reasons for their exclusion</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK591345/table/niceng217er32.appk.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng217er32.appk.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for Exclusion</th></tr></thead><tbody><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Al-Banji, M. H., Zahr, D. K., Jan, M. M., Lennox-gastaut syndrome: Management update, Neurosciences, 20, 207–212, 2015 [<a href="/pmc/articles/PMC4710331/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4710331</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26166587" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26166587</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review, references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arzimanoglou, A., Ferreira, J. A., Satlin, A., Mendes, S., Williams, B., Critchley, D., Schuck, E., Hussein, Z., Kumar, D., Dhadda, S., et al, Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: an interim analysis from a multicenter, randomized, active-controlled, open-label study, European journal of paediatric neurology: EJPN, 20, 393–402, 2016 [<a href="https://pubmed.ncbi.nlm.nih.gov/26805435" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26805435</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes were reported</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arzimanoglou, A., French, J., Blume, W. T., Cross, J. H., Ernst, J. P., Feucht, M., Genton, P., Guerrini, R., Kluger, G., Pellock, J. M., Perucca, E., Wheless, J. W., Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology, The Lancet Neurology, 8, 82–93, 2009 [<a href="https://pubmed.ncbi.nlm.nih.gov/19081517" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19081517</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review; references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Auvin, S., Williams, B., McMurray, R., Kumar, D., Perdomo, C., Malhotra, M., Novel seizure outcomes in patients with Lennox-Gastaut syndrome: Post hoc analysis of seizure-free days in rufinamide Study 303, Epilepsia Open, 4, 275–280, 2019 [<a href="/pmc/articles/PMC6546073/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6546073</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31168494" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31168494</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis of Arzimanoglou 2019</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Borrelli, S., El Tahry, R., Therapeutic approach to Lennox-Gastaut syndrome: a systematic review, Acta Neurologica Belgica, 119, 315–324, 2019 [<a href="https://pubmed.ncbi.nlm.nih.gov/31286465" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31286465</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; insufficient data to allow extraction</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Caraballo, R. H., Flesler, S., Reyes Valenzuela, G., Fortini, S., Chacon, S., Ross, L., Noli, D., Sulthiame add-on therapy in children with Lennox-Gastaut syndrome: A study of 44 patients, Seizure, 62, 55–58, 2018 [<a href="https://pubmed.ncbi.nlm.nih.gov/30286409" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30286409</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Caraballo, R. H., Fortini, S., Fresler, S., Armeno, M., Ariela, A., Cresta, A., Mestre, G., Escobal, N., Ketogenic diet in patients with Lennox-Gastaut syndrome, Seizure, 23, 751–5, 2014 [<a href="https://pubmed.ncbi.nlm.nih.gov/25011392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25011392</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Carmant, L., Whiting, S., Lennox-Gastaut syndrome: An update on treatment, Canadian Journal of Neurological Sciences, 39, 702–711, 2012 [<a href="https://pubmed.ncbi.nlm.nih.gov/23227575" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23227575</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review; references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chung, S. S., Gidal, B. E., Lemming, O. M., Karnik-Henry, M., Hackler, E., Tolbert, D., Tworek, D. M., Sayeed, S., Combination AED treatment with clobazam in patients with lennox-gastaut syndrome: post hoc analyses of the contain study, Neurology, 90, 2018
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Conry, J. A., Ng, Y. T., Kernitsky, L., Mitchell, W. G., Veidemanis, R., Drummond, R., Isojarvi, J., Lee, D., Paolicchi, J. M., Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years, Epilepsia, 55, 558–567, 2014 [<a href="/pmc/articles/PMC4303987/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4303987</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24580023" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24580023</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open-label extension study; all participants received clobazam and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Coppola, G., Grosso, S., Franzoni, E., Veggiotti, P., Zamponi, N., Parisi, P., Spalice, A., Habetswallner, F., Fels, A., Capovilla, G., Verrotti, A., Mangano, S., Balestri, A., Curatolo, P., Pascotto, A., Rufinamide in children and adults with Lennox-Gastaut syndrome: first Italian multicenter experience, Seizure, 19, 587–91, 2010 [<a href="https://pubmed.ncbi.nlm.nih.gov/20888268" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20888268</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Cramer, J. A., Sapin, C., Francois, C., Indirect comparison of clobazam and other therapies for Lennox-Gastaut syndrome, Acta Neurologica Scandinavica, 128, 91–9, 2013 [<a href="https://pubmed.ncbi.nlm.nih.gov/23410109" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23410109</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes were reported. This study performed indirect comparisons and, due to differences in how outcomes were reported across studies, only a Cohen’s <i>d</i> effect size was calculated and reported. Studies included in this paper had already been included in the evidence review</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Donaldson, J. A., Glauser, T. A., Olberding, L. S., Lamotrigine adjunctive therapy in childhood epileptic encephalopathy (the Lennox Gastaut syndrome), Epilepsia, 38, 68–73, 1997 [<a href="https://pubmed.ncbi.nlm.nih.gov/9024186" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9024186</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Duchowny, M., Gilman, J., Messenheimer, J., Womble, G., Risner, M., Ayala, R., Konkol, R., Campbell, R., Crumrine, P. K., Cruse, R. P., Delgado, M., Fountain, N., Enlow, T., Fakhoury, T. A., Casadonte, J., Frank, L. M., Graf, W., Griebel, M. L., Griesemer, D. A., Wannamaker, B., Olson, D. M., Silverstein, F., Hurst, D., Jackson, A., Laxer, K. D., Bluestone, D., Maria, B., Lassiter, A., Levisohn, P. M., Libenson, M., Mitchell, W., Montouris, G., Murphy, J., Oommen, K. J., Park, Y. D., Parks, B. R., Snodgrass, S., Pellock, J. M., Ramsay, E., Ritter, F. J., Schimschock, J. R., Khan, A., Shuman, R., Tennison, M., Cheng, R. D., Turk, W., Wise, M. S., Bebin, E., Gonzalez, A., Ruiz, M., Gonzalez, R. C., Llamosa, G., Saiers, J., Long-term tolerability and efficacy of lamotrigine in pediatic patients with epilepsy, Journal of Child Neurology, 17, 278–285, 2002 [<a href="https://pubmed.ncbi.nlm.nih.gov/12088084" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12088084</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open label study; all participants received lamotrigine and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Eriksson, A. S., Nergårdh, A., Hoppu, K., The efficacy of lamotrigine in children and adolescents with refractory generalized epilepsy: a randomized, double-blind, crossover study, Epilepsia, 39, 495–501, 1998 [<a href="https://pubmed.ncbi.nlm.nih.gov/9596201" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9596201</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment effects were not reported by treatment arm for the Lennox-Gastaut subgroup of children</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Freeman, J.M., Vining, E.P., Kossoff, E.H., Pyzik, P.L., Ye, X., Goodman, S.N., A blinded, crossover study of the efficacy of the ketogenic diet, Epilepsia, 50, 322–325, 2009 [<a href="https://pubmed.ncbi.nlm.nih.gov/18717710" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18717710</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment effects were not reported by treatment arm</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glauser, T. A., Levisohn, P. M., Ritter, F., Sachdeo, R. C., Topiramate in Lennox-Gastaut syndrome: Open-label treatment of patients completing a randomized controlled trial, Epilepsia, 41, S86–S90, 2000 [<a href="https://pubmed.ncbi.nlm.nih.gov/10768308" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10768308</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open-label extension study; all participants received topiramate and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glauser, T. A., Sachdeo, R. C., Ritter, F. J., Reife, R., Lim, P., A double-blind trial of topiramate in Lennox-Gastaut syndrome (LGS), Epilepsia, 38
|
|
Suppl 3, 131, 1997
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glauser, T., Kluger, G., Krauss, G., Arroyo, S., Effects of rufinamide on the frequency of different seizure types in patients with Lennox-Gastaut syndrome: a long-term study, Epilepsia, 48
|
|
Suppl 7, 156, 2007
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glauser, T., Kluger, G., Sachdeo, R., Krauss, G., Perdomo, C., Arroyo, S., Open-label extension study of the efficacy and safety of rufinamide adjunctive therapy in patients with Lennox-Gastaut syndrome, Epilepsia, 46
|
|
Suppl 6, 408, 2005
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glauser, T., Kluger, G., Sachedo, R., Krauss, G., Perdomo, C., Arroyo, S., Efficacy and safety of rufinamide adjunctive therapy in patients with Lennox-Gastaut syndrome (LGS): a multicenter, randomized, double-blind, placebo-controlled, parallel trial, Neurology, 64, 1826, 2005
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Guerreiro, M. M., Manreza, M. L., Scotoni, A. E., Silva, E. A., Guerreiro, C. A., Souza, E. A., Ferreira, V. B., Reed, U. C., Diament, A., Trefiglio, R., Chiu, H. C., Bacaltchuk, J., A pilot study of topiramate in children with Lennox-Gastaut syndrome, Arquivos de Neuro-Psiquiatria, 57, 167–75, 1999 [<a href="https://pubmed.ncbi.nlm.nih.gov/10412513" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10412513</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Isojarvi, J., Gidal, B. E., Chung, S., Wechsler, R. T., Optimizing clobazam treatment in patients with Lennox-Gastaut syndrome, Epilepsy & Behavior, 78, 149–154, 2018 [<a href="https://pubmed.ncbi.nlm.nih.gov/29202277" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29202277</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis of Conry 2009 and Ng 2011</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Isojarvi, J., Lee, D., Peng, G., Sperling, M. R., Clobazam-treated patients with Lennox-Gastaut syndrome experienced fewer seizure-related injuries than placebo patients during trial OV-1012, Epilepsia, 57, e113–e116, 2016 [<a href="/pmc/articles/PMC5021111/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5021111</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27145465" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27145465</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis of Ng 2011</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Jensen, P. K., Felbamate in the treatment of Lennox-Gastaut syndrome, Epilepsia, 35, S54–S57, 1994 [<a href="https://pubmed.ncbi.nlm.nih.gov/8039473" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8039473</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kim, S. H., Eun, S. H., Kang, H. C., Kwon, E. J., Byeon, J. H., Lee, Y. M., Lee, J. S., Eun, B. L., Kim, H. D., Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome, Seizure, 21, 288–91, 2012 [<a href="https://pubmed.ncbi.nlm.nih.gov/22421185" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22421185</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kluger, G., Bauer, B., Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy), Neuropsychiatric Disease and Treatment, 3, 3–11, 2007 [<a href="/pmc/articles/PMC2654531/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2654531</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19300535" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19300535</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review; references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kluger, G., Glauser, T., Sachdeo, R., Krauss, G., Perdomo, C., Arroyo, S., Short-term and long-term efficacy and safety of rufinamide as adjunctive therapy in patients with inadequately controlled Lennox-Gastaut syndrome, Epilepsia, 47
|
|
Suppl 3, 139, 2006
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kluger, G., Glauser, T., Krauss, G., Seeruthun, R., Perdomo, C., Arroyo, S., Adjunctive rufinamide in Lennox-Gastaut syndrome: A long-term, open-label extension study, Acta Neurologica Scandinavica, 122, 202–208, 2010 [<a href="https://pubmed.ncbi.nlm.nih.gov/20199521" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20199521</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open-label extension study; all participants received rufinamide and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kothare, S., Kluger, G., Sachdeo, R., Williams, B., Olhaye, O., Perdomo, C., Bibbiani, F., Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: Phase III trial results and real-world clinical data, Seizure, 47, 25–33, 2017 [<a href="https://pubmed.ncbi.nlm.nih.gov/28284045" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28284045</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; observational studies were also included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Krauss, G. L., Glauser, T., Kluger, G., Arroyo, S., Long-term safety of rufinamide in patients with Lennox-Gastaut syndrome, Epilepsia, 48
|
|
Suppl 6, 359, 2007
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Montouris, G. D., Wheless, J. W., Glauser, T. A., The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome, Epilepsia, 55
|
|
Suppl 4, 10–20, 2014 [<a href="https://pubmed.ncbi.nlm.nih.gov/25284033" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25284033</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; observational studies were also included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Mullens, L., Gallagher, J., Improved neurological function accompanies effective control of the Lennox-Gastaut syndrome with Lamictal: results of a multinational, placebo-controlled trial, Epilepsia, 37
|
|
Suppl 5, 163, Abstract no: 6.47, 1996
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ng, Y. T., Conry, J., Mitchell, W. G., Buchhalter, J., Isojarvi, J., Lee, D., Drummond, R., Chung, S., Clobazam is equally safe and efficacious for seizures associated with Lennox-Gastaut syndrome across different age groups: Post hoc analyses of short- and long-term clinical trial results, Epilepsy and Behavior, 46, 221–226, 2015 [<a href="https://pubmed.ncbi.nlm.nih.gov/25940107" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25940107</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis of Conry 2009 and Ng 2011</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ng, Y. T., Conry, J., Paolicchi, J., Kernitsky, L., Mitchell, W., Drummond, R., Isojarvi, J., Lee, D., Owen, R., Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study, Epilepsy & Behavior, 25, 687–694, 2012 [<a href="https://pubmed.ncbi.nlm.nih.gov/23141144" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23141144</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open-label extension study; all participants received clobazam and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ohtsuka, Y., Yoshinaga, H., Shirasaka, Y., Takayama, R., Takano, H., Iyoda, K., Long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome receiving adjunctive rufinamide therapy: An open-label study following a randomized clinical trial, Epilepsy Research, 121, 1–7, 2016 [<a href="https://pubmed.ncbi.nlm.nih.gov/26827266" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26827266</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Open-label extension study; all participants received rufinamide and no comparison group was included</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Oletsky, H., Kelley, K., Stertz, B., Reeves-Tyer, P., Flamini, R., Malow, B., Theodore, W., Nag, D, Garg, et al, The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome (LGS), Epilepsia, 37
|
|
Suppl 5, 155, Abstract no: 6.13, 1996 [<a href="https://pubmed.ncbi.nlm.nih.gov/10210023" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10210023</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Paolicchi, J. M., Ross, G., Lee, D., Drummond, R., Isojarvi, J., Clobazam and Aggression-Related Adverse Events in Pediatric Patients with Lennox-Gastaut Syndrome, Pediatric Neurology, 53, 338–342, 2015 [<a href="https://pubmed.ncbi.nlm.nih.gov/26245776" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26245776</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc study for Ng 2011</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Purcarin, G., Ng, Y. T., Experience in the use of clobazam in the treatment of Lennox-Gastaut syndrome, Therapeutic Advances in Neurological Disorders, 7, 169–176, 2014 [<a href="/pmc/articles/PMC3994921/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3994921</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24790647" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24790647</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review; references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sachdeo, S., Sachdeo, R. C., Kugler, S., An open label evaluation of topiramate in Lennox-Gastaut syndrome, Epilepsia, 37
|
|
Suppl 5, 112, 1996
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Stafstrom, C. E., Update on the management of Lennox-Gastaut syndrome with a focus on rufinamide, Neuropsychiatric Disease and Treatment, 5, 547–551, 2009 [<a href="/pmc/articles/PMC2773286/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2773286</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19898669" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19898669</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review; references checked for inclusion</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Tolbert, D., Harris, S. I., Bekersky, I., Lee, D., Isojarvi, J., Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome, Epilepsy and Behavior, 37, 11–15, 2014 [<a href="https://pubmed.ncbi.nlm.nih.gov/24949576" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24949576</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes reported</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Trevathan, E., Motte, J., Arvidsson, J., Manasco, P., Mullens, L., Safety and tolerability of adjunctive Lamictal<sup>®</sup> for the treatment of the Lennox-Gastaut syndrome: results of a multinational, double-blind, placebo-controlled trial, Epilepsia, 37
|
|
Suppl 5, 202, 1996
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Trevathan, E., Mullens, E. L., Manasco, P., Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome, New England Journal of Medicine, 339, 851–2, 1998 [<a href="https://pubmed.ncbi.nlm.nih.gov/9750085" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9750085</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Vajda, F. J., Bladin, P. F., Parsons, B. J., Clinical experience with clobazam: a new 1,5 benzodiazepine in the treatment of refractory epilepsy, Clinical and experimental neurology, 21, 177–182, 1985 [<a href="https://pubmed.ncbi.nlm.nih.gov/3843217" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3843217</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sample included patients who did not have Lennox-Gastaut syndrome and results are not reported separately</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Vassella, F., Rüdeberg, A., Da Silva, V., Pavlincova, E., Double-blind study on the anti-convulsive effect of phenobarbital and valproate in the Lennox syndrome, Schweizerische medizinische wochenschrift, 108, 713–716, 1978 [<a href="https://pubmed.ncbi.nlm.nih.gov/347569" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 347569</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study in German</td></tr><tr><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
You, S. J., Kang, H. C., Kim, H. D., Lee, H. S., Ko, T. S., Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience, Brain & Development, 30, 287–90, 2008 [<a href="https://pubmed.ncbi.nlm.nih.gov/17959327" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17959327</span></a>]
|
|
</td><td headers="hd_h_niceng217er32.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not a randomised trial</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal104 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|