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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003ELisdexamfetamine dimesylate was statistically superior to osmotic controlled-release methylphenidate in a forced-dose study of adolescents with attention-deficit\/hyperactivity disorder but failed to meet standards of statistical significance in a flexible-dose version of the study.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EADHD\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elisdexamfetamine dimesylate\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELDX\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emethylphenidate\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOROS-MPH\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eattention-deficit\/hyperactivity disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EClinical Global Impressions\u2013Improvement\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Echild \u0026amp; adolescent psychiatry\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epsychiatry \u0026amp; psychology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EAmphetamine-based treatments such as lisdexamfetamine dimesylate (LDX) and methylphenidate (MPH)-based agents are first-line treatments for adolescents with attention-deficit\/hyperactivity disorder (ADHD), and each has been proven superior to placebo in numerous trials [Woolraich M et al. \u003Cem\u003EPediatrics\u003C\/em\u003E. 2011; Atkinson M, Hollis C. \u003Cem\u003EArch Dis Child Educ Pract Ed\u003C\/em\u003E. 2010]. A meta-analysis of clinical trials reported that amphetamine-based agents have greater effects than MPH-based agents [Faraone SV, Buitelaar J. \u003Cem\u003EEur Child Adolesc Psychiatry\u003C\/em\u003E. 2010]. Another meta-analysis indicated that amphetamine-based treatments were associated with higher probability of response when compared with various MPH-based agents [Roskell NS et al. \u003Cem\u003ECurr Med Res Opin\u003C\/em\u003E. 2014]. Although such systematic assessments of existing data provide useful information about differential efficacy, they are indirect by nature.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EJeffrey Newcorn, MD, Icahn School of Medicine at Mount Sinai, New York, New York, USA, and colleagues conducted 2 studies directly comparing LDX with osmotic controlled-release MPH (OROS-MPH) in adolescents with ADHD. The primary end point was efficacy, as measured with the ADHD Rating Scale IV. Study 1 [NCT015529115] was an 8-week flexible-dose study, and study 2 [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01552902\u0026amp;atom=%2Fspmdc%2F15%2F11%2F5.atom\u0022\u003ENCT01552902\u003C\/a\u003E] was a 6-week forced-dose titration study. In study 1, patients were randomized 2:2:1 to once-daily LDX 30 to 70 mg, OROS-MPH 18 to 72 mg, or placebo. In study 2, the randomization was 2:2:1 to once-daily LDX 70 mg, OROS-MPH 72 mg, or placebo.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe least squares mean\u2005\u00b1\u2005standard error of the mean was greater with LDX than with OROS-MPH in the flexible-dose study, but the difference was not significant (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The benefit of LDX over OROS-MPH was significant in the forced-dose study.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16874\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16874\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16874\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EEfficacy End Point Data From ADHD Studies\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-12\u0022\u003EThe key secondary end point was Clinical Global Impressions\u2013Improvement scale score. Similar to what was seen with the ADHD scores from the 2 agents in each study, the scale score was greater with LDX than with OROS-MPH in the flexible-dose study (\u003Ca id=\u0022xref-table-wrap-1-2\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), but the difference was not significant. In the forced-dose study, the score was significantly greater with LDX than with OROS-MPH.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003ELDX was approved by the US FDA in 2007 for use in patients \u22656 years old with ADHD. The safety and tolerability profile of LDX has been consistent across clinical trials, with small increases in heart rate and\/or blood pressure observed. The most frequently observed treatment-emergent adverse events (TEAEs) associated with LDX treatment include decreased appetite, decreased weight, and insomnia [Coghill D et al. \u003Cem\u003EEur Neuropsychopharmacol\u003C\/em\u003E. 2013; Findling RL et al. \u003Cem\u003EJ Am Acad Child Adolesc Psychiatry\u003C\/em\u003E. 2011].\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EDr Newcorn and colleagues evaluated the safety and tolerability of LDX and OROS-MPH as secondary end points. Safety assessments included recording adverse events and vital signs. In the flexible-dose study, TEAEs were reported in 83.2% of patients receiving LDX, compared with 82.1% receiving OROS-MPH. In the forced-dose study, 66.5% of patients receiving LDX reported TEAEs, compared with 58.9% of patients receiving OROS-MPH. In the placebo groups, 63.7% and 44.5% of patients reported TEAEs in the flexible- and forced-dose studies, respectively. Consistent with known effects of LDX and OROS-MPH, TEAEs that occurred in \u226510% of patients included decreased appetite and headache with LDX and OROS-MPH in both studies, decreased weight with LDX in both studies and with OROS-MPH in the forced-dose study, and irritability with LDX in the flexible-dose study.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EDr Newcorn and colleagues concluded that LDX was not statistically superior to OROS-MPH in a flexible-dose design but was statistically superior in a forced-dose design, while the safety and tolerability profiles of both agents were consistent with those observed in previous studies.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/11\/5.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzli82\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzli82\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}