{"id":17498,"date":"2011-12-21T20:20:38","date_gmt":"2011-12-22T01:20:38","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=17498"},"modified":"2011-12-21T20:30:13","modified_gmt":"2011-12-22T01:30:13","slug":"xxx-years-of-experience","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/12\/21\/xxx-years-of-experience\/","title":{"rendered":"over xxx years of experience&#8230;"},"content":{"rendered":"<div align=\"center\"><a href=\"http:\/\/embarc.utsouthwestern.edu\/about.cfm\" target=\"_blank\"><img decoding=\"async\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/embarc-1.gif\" \/><\/a><\/div>\n<p align=\"justify\">I have repeatedly teased about Dr. Trivedi&#8217;s difficulty finishing tasks. His <strong><font color=\"#200020\">IMPACTS<\/font><\/strong> study was never completed. In <strong><font color=\"#200020\">STAR*D<\/font><\/strong>, they never published their primary efficacy results. <strong><font color=\"#200020\">CO-MED<\/font><\/strong> came in way late and was decidedly negative. <strong><font color=\"#200020\">TMAP<\/font><\/strong> landed in a courtroom. But in <strong><font color=\"#200020\">EMBARC<\/font><\/strong>, his new genetics study, he didn&#8217;t even finish his web-site.<\/p>\n<div align=\"justify\">Why, pray tell, was I looking at the <u><a target=\"_blank\" href=\"http:\/\/embarc.utsouthwestern.edu\/dallas.cfm\"><strong><font color=\"#200020\">EMBARC<\/font><\/strong><\/a><\/u> web site? I had something rolling around I wanted to say about the NIMH study. This is the one where he&#8217;s looking for <em>biosignatures<\/em> to predict the response to antidepressants. Here&#8217;s what I thought they were going to do: Put people on either Citalopram or Bupropion measuring a gajillion potential biomarkers, then crossover and put the non-responders on the other drug &#8211; all the while collecting the gajillion biomarkers looking for some thing [or things] that would predict response. That&#8217;s what I remembered. But when I started to look for the details&#8230;<\/div>\n<ul>\n<div align=\"justify\"><sup><strong><a target=\"_blank\" href=\"http:\/\/projectreporter.nih.gov\/project_info_description.cfm?aid=8333667&#038;icde=10806926\"><u><font color=\"#200020\">NIMH RePORTER<\/font><\/u><\/a>:<\/strong> We propose a comparative effectiveness trial of three  mechanistically distinct treatments for MDD [citalopram, bupropion, and  cognitive behavioral therapy] in which we will assess a comprehensive  array of carefully selected clinical [i.e. anxious depression, early  life trauma, &amp; gender] and biological [i.e. genetic, neuroimaging,  serum, epigenetic &amp; qEEG] moderators and mediators of outcome. Using  innovative statistical approaches the identified moderators and  mediators will then be used to develop a differential depression  treatment response index [DTRI]. The proposed study is a randomized  two-stage trial [Stagel:12 wks; Stage2: 12 wks] design with 675 MDD  patients [with a history of one adequate trial of an SSRI except  citalopram] assigned to one of three treatment conditions [n=225 each].  This two stage approach is similar to a Sequential Multiple Assignment  Randomized Trial [SMART] design. This study will examine multiple carefully  selected clinical and biological markers, using both existing state  of-the-art technologies as well as pioneering, innovative approaches.  Evaluation of the usefulness of these markers in a trial with three  different treatments will assist in generating a depression treatment  response index [DTRI]. The DTRI will help clinicians match treatments to  patients with MDD, resulting in timely selection of treatments best  suited for individual patients. Results from this study could  significantly improve the treatment of patients with MDD.&amp;<\/sup><\/div>\n<\/ul>\n<ul>\n<div align=\"justify\"><sup><strong><font color=\"#200020\"><a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01407094?term=trivedi&#038;rank=13\"><u>clinicaltrials.gov<\/u><\/a>:<\/font><\/strong> The current study is designed to identify biomarkers for the prediction  of differential treatment outcomes between the SSRI antidepressant  citalopram [CIT] and placebo [PBO] in a randomized trial for patients  with MDD. In addition, a second stage will collect data to explore  moderators and mediators of treatment outcomes between pharmacologically  distinct active treatment arms: citalopram [CIT], a serotonergic  antidepressant or bupropion [BUP], a nonserotonergic antidepressant&#8230; In  the first stage, patients will receive an 8&minus;week course of treatment in  one of the two study arms. As part of the Sequential Multiple Assignment  Randomized Trial [SMART] design patients that have not achieved  response at the end of 8 weeks to their stage one treatment, defined by  &lt; 50% improvement on the Clinical Global Improvement scale [CGI],  will be switched to Stage 2 treatment [8 weeks]. Patients who have  achieved satisfactory response [&gt;= 50% improvement on the CGI] will  be continued on treatment for an additional 8 weeks.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">After reading those two descriptions, I haven&#8217;t got any idea what they&#8217;re going to do. But I&#8217;ll make my comment anyway, just in the offhand case that when the study becomes clear, it fits. I think the hypothesis for the study is that there is some genetic factor that has to do with whether or not you respond to one antidepressant or another. I can&#8217;t find solid evidence for such a notion, I just know it&#8217;s a widely held hypothesis. So they&#8217;re going to study a group of depressed people hypothesizing that the group contains <strong><font color=\"#400040\">Citalopram Responders<\/font><\/strong> and <strong><font color=\"#400040\">Bupropion Responders<\/font><\/strong> which they&#8217;re going to identify using biosignatures. My comment was going to be &quot;Don&#8221;t bother. You&#8217;ve already done the study.&quot; Remember <strong><font color=\"#200020\">CO-MED<\/font><\/strong>?<\/div>\n<blockquote>\n<div align=\"center\"><font color=\"#200020\"> <a target=\"_blank\" href=\"http:\/\/ajp.psychiatryonline.org\/cgi\/content\/short\/appi.ajp.2011.10111645v1?rss=1\"><u><strong><font color=\"#200020\">Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and Long-Term Outcomes of a Single-Blind Randomized Study<\/font><\/strong><\/u><\/a><br \/>               <strong><font color=\"#200020\">American Journal of Psychiatry<\/font><\/strong><br \/>             <sup>by  A. John Rush, M.D.,  Madhukar H. Trivedi, M.D.,  Jonathan W. Stewart,  M.D.,  Andrew A. Nierenberg, M.D.,  Maurizio Fava, M.D.,  Benji T.  Kurian, M.D.,  Diane Warden, Ph.D.,  David W. Morris, Ph.D.,  James F.  Luther, M.A.,  Mustafa M. Husain, M.D.,  Ian A. Cook, M.D.,  Richard C.  Shelton, M.D.,  Ira M. Lesser, M.D.,  Susan G. Kornstein, M.D., and   Stephen R. Wisniewski, Ph.D.<\/sup><br \/>               May 2, 2011<\/font><\/div>\n<p>       <\/p>\n<div align=\"justify\"><sup><strong><font color=\"#200020\"><u>Objective<\/u>:<\/font><\/strong>  Two antidepressant medication combinations were compared with selective  serotonin reuptake inhibitor monotherapy to determine whether either  combination produced a higher remission rate in first-step acute-phase  (12 weeks) and long-term (7 months) treatment.<br \/>                <strong><font color=\"#200020\"><u>Method<\/u>:<\/font><\/strong>  The single-blind, prospective, randomized trial enrolled 665  outpatients at six primary and nine psychiatric care sites. Participants  had at least moderately severe nonpsychotic chronic and\/or recurrent  major depressive disorder. Escitalopram (up to 20 mg\/day) plus placebo,  sustained-release bupropion (upto 400 mg\/day) plus escitalopram (up to  20 mg\/day), or extended-release venlafaxine (up to 300 mg\/day) plus  mirtazapine (up to 45 mg\/day) was delivered (1:1:1 ratio) by using  measurement-based care.The primary outcome was remission, defined as  ratings of less than 8 and less than 6 on the last two consecutive  applications of the 16-item Quick Inventory of Depressive  Symptomatology-Self-Report. Secondary outcomes included side effect  burden, adverse events, quality of life, functioning, and attrition.<br \/>               <strong><font color=\"#200020\"><u>Results<\/u>:<\/font><\/strong>  Remission and response rates and most secondary outcomes were not  different among treatment groups at 12 weeks. The remission rates were  38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and  37.7% for venlafaxine-mirtazapine, and the response rates were  51.6%&ndash;52.4%. The mean number of worsening adverse events was higher for  venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7  months, remission rates (41.8%&ndash;46.6%), response rates (57.4%&ndash;59.4%), and  most secondary outcomes were not significantly different.<br \/>                <strong><font color=\"#200020\"><u>Conclusions<\/u>:<\/font><\/strong>  Neither medication combination outperformed monotherapy. The  combination of extended-release venlafaxine plus mirtazapine may have a  greater risk of adverse events.<\/sup><\/div>\n<\/blockquote>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" height=\"196\" width=\"520\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/co-med-3.gif\" \/><\/div>\n<p align=\"justify\"><em>I&#8217;m assuming that Citalopram [Celexa] and Escitalopram [Lexapro] are bioequivalent drugs.<\/em> So, if there were two populations [<strong><font color=\"#400040\">Citalopram Responders<\/font><\/strong> and <strong><font color=\"#400040\">Bupropion Responders<\/font><\/strong>], in <strong><font color=\"#200020\">CO-MED<\/font><\/strong> there would&#8217;ve been a greater response to <strong><font color=\"#400040\">Escitalopram+Bupropion<\/font><\/strong> than to <strong><font color=\"#400040\">Escitalopram+Placebo<\/font><\/strong>. It didn&#8217;t happen. <\/p>\n<div align=\"justify\">Thus far, attempts to squeeze more out of the antidepressants than they offer up front haven&#8217;t been very successful. I doubt that either the <a href=\"http:\/\/embarc.utsouthwestern.edu\/dallas.cfm\" target=\"_blank\"><u><strong><font color=\"#200020\">EMBARC<\/font><\/strong><\/u><\/a> study or <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3036635\/\" target=\"_blank\"><u><strong><font color=\"#200020\">iSPOT<\/font><\/strong><\/u><\/a> will be any different. I suppose if you think the only thing you have to offer is drugs, hope springs eternal&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>I have repeatedly teased about Dr. Trivedi&#8217;s difficulty finishing tasks. His IMPACTS study was never completed. In STAR*D, they never published their primary efficacy results. CO-MED came in way late and was decidedly negative. TMAP landed in a courtroom. But in EMBARC, his new genetics study, he didn&#8217;t even finish his web-site. Why, pray tell, [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-17498","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/17498","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=17498"}],"version-history":[{"count":18,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/17498\/revisions"}],"predecessor-version":[{"id":17516,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/17498\/revisions\/17516"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=17498"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=17498"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=17498"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}