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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\u003EThe first-ever placebo-controlled trial in major depressive disorder with mixed features demonstrated that lurasidone, an atypical antipsychotic agent, was efficacious in reducing depressive symptoms in these patients and was also well tolerated when compared with placebo.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emajor depressive disorder with mixed features\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elurasidone\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eatypical antipsychotic\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMADRS total score\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECGI-S score\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\u003ETrisha Suppes, MD, PhD, Stanford University School of Medicine, Stanford, California, USA, presented the results of a randomized controlled trial in adults with major depressive disorder (MDD) with mixed features, demonstrating that lurasidone significantly reduced depressive symptoms in these patients when compared with placebo [RESOLVE2; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01423240\u0026amp;atom=%2Fspmdc%2F15%2F11%2F11.atom\u0022\u003ENCT01423240\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAccording to the \u003Cem\u003EDSM-V\u003C\/em\u003E, the specifier \u201cwith mixed features\u201d can be added to a diagnosis of MDD to indicate symptoms of both depression and subthreshold mania or hypomania. Although mixed features are present in 20% to 40% of individuals with MDD, this patient population is challenging to manage because of a lack of established treatments for this disease subset, Dr Suppes said. In addition to its poor treatment response, MDD with mixed features is associated with greater symptom severity and increased suicide risk. Evidence also suggests that this disease subset may be best classified within the spectrum of bipolar disorders [Vieta E, Valent\u00ed M. \u003Cem\u003EJ Affect Disord\u003C\/em\u003E. 2013].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EConsequently, this multinational double-blind study was designed to investigate the efficacy and safety of lurasidone in patients with unipolar MDD with mixed (subthreshold hypomanic) features. Lurasidone is an atypical antipsychotic with efficacy in the treatment of bipolar depression, as both monotherapy and adjunctive therapy [Loebel A et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E. 2014a, 2014b].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EInclusion criteria included patients who met the criteria for MDD according to the \u003Cem\u003EDSM-IV-TR\u003C\/em\u003E, who had a Montgomery-Asberg Depression Rating Scale (MADRS) score \u2265\u200526, and who were experiencing 2 or 3 manic symptoms per the \u003Cem\u003EDSM-V\u003C\/em\u003E criteria on most days over at least the 2 weeks prior to screening. Exclusion criteria included any lifetime history of bipolar I manic episodes or any mixed manic episodes.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETwo hundred and eleven study participants were randomly assigned to 6 weeks of treatment with either flexible doses of lurasidone (20 to 60 mg\/d; n\u2005=\u2005109) or placebo (n\u2005=\u2005100). The primary end point was the change in MADRS total score from baseline to 6 weeks, and the key secondary end point was the change in Clinical Global Impression\u2013Severity score from baseline to 6 weeks. Responder rates were characterized as \u2265\u200550% reduction from baseline in MADRS total score.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ELurasidone treatment was associated with a significantly greater mean reduction in MADRS total score (20.5 vs 13.0; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001; effect size, 0.80; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) and Clinical Global Impression\u2013Severity score (1.83 vs 1.18; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001; effect size, 0.60) compared with placebo from baseline to 6 weeks.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/11\/11\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Change in MADRS ScoreMixed model for repeated measures analysis (modified intent-to-treat population).LS, least squares; MADRS, Montgomery-Asberg Depression Rating Scale.*P\u0026#x2005;\u0026amp;lt;\u0026#x2005;.05; **P\u0026#x2005;\u0026amp;lt;\u0026#x2005;.01; ***P\u0026#x2005;\u0026amp;lt;\u0026#x2005;.0001.Reproduced with permission from T Suppes, MD, PhD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-885700196\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Change in MADRS ScoreMixed model for repeated measures analysis (modified intent-to-treat population).LS, least squares; MADRS, Montgomery-Asberg Depression Rating Scale.\u0026amp;lt;sup\u0026amp;gt;*\u0026amp;lt;\/sup\u0026amp;gt;\u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt;\u0026#x2005;\u0026amp;amp;lt;\u0026#x2005;.05; \u0026amp;lt;sup\u0026amp;gt;**\u0026amp;lt;\/sup\u0026amp;gt;\u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt;\u0026#x2005;\u0026amp;amp;lt;\u0026#x2005;.01; \u0026amp;lt;sup\u0026amp;gt;***\u0026amp;lt;\/sup\u0026amp;gt;\u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt;\u0026#x2005;\u0026amp;amp;lt;\u0026#x2005;.0001.Reproduced with permission from T Suppes, MD, PhD.\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/11\/11\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/11\/11\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/11\/11\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16864\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\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EChange in MADRS Score\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EMixed model for repeated measures analysis (modified intent-to-treat population).\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003ELS, least squares; MADRS, Montgomery-Asberg Depression Rating Scale.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003E\u003Csup\u003E*\u003C\/sup\u003E\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05; \u003Csup\u003E**\u003C\/sup\u003E\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.01; \u003Csup\u003E***\u003C\/sup\u003E\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EReproduced with permission from T Suppes, MD, PhD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-13\u0022\u003EAt 6 weeks, the responder rate for the lurasidone group was also higher (64.8% vs 30.0%; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001; number needed to treat, 3).\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EThe mean change from baseline to 6 weeks in the Hamilton Anxiety Rating Scale was \u22125.4 with placebo and \u22129.9 with lurasidone (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001) and in the Young Mania Rating Scale, \u22125.4 and \u22127.0, respectively (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001). The Sheehan Disability Scale was significantly reduced with lurasidone vs placebo (\u221211.2 vs \u22126.4; \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001), and 3 of its subscales (work, social life, family disability) were also significantly reduced (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001).\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EAdverse events resulting in discontinuation were reported in 2.8% of patients receiving lurasidone, compared with 4.9% of those receiving placebo. Nausea was the only adverse event reported, with an incidence \u2265\u20052% (and greater than placebo) in patients receiving lurasidone (6.4% vs 2.0%). The incidence of somnolence, including hypersomnia, sedation, and somnolence, was 5.5% and 1.0% in the lurasidone and placebo groups, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EThis is the first reported placebo-controlled trial in adults with MDD with mixed features, Dr Suppes said, and the results demonstrate lurasidone\u2019s efficacy in reducing depressive symptoms in these patients. The safety and tolerability of lurasidone in this study were also consistent with those previously reported in clinical trials in bipolar depression and schizophrenia.\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\/11.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_figures.js?nzlige\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_openurl.js?nzlige\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}