{"id":37872,"date":"2013-06-23T01:48:14","date_gmt":"2013-06-23T05:48:14","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=37872"},"modified":"2013-06-23T01:51:59","modified_gmt":"2013-06-23T05:51:59","slug":"rest-my-case","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/06\/23\/rest-my-case\/","title":{"rendered":"rest my case&#8230;"},"content":{"rendered":"\n<ul>\n<div class=\"small\"><font color=\"#400040\">Oh sleep! it is a gentle thing,<br \/>                         Beloved from pole to pole!<br \/>                         To Mary Queen the praise be given!<br \/>                         She sent the gentle sleep from Heaven,<br \/>                         That slid into my soul.<\/font><\/div>\n<div align=\"center\" class=\"small\"><font color=\"#400040\">The Rime Of The Ancient Mariner by by Samuel Taylor Coleridge<\/font><\/div>\n<\/ul>\n<p align=\"justify\"><img decoding=\"async\" hspace=\"4\" height=\"180\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/mariner-1.gif\" \/>Sleep disturbance is a much complained of symptom among the depressed, from the early morning awakening of Melancholic to the long nights of the afflicted that feels like the albatross around the neck of Colridge&#8217;s cursed mariner. &quot;If I could only sleep,&quot; is a constant refrain in the clinics and offices of psychiatrists and primary care physicians alike. And one of the earliest signs of relief in depression is some improvement in sleep patterns. Trivedi et al&#8217;s latter-day pooled analysis of Seroquel XR&reg; in MDD mentioned in the last post is about just that &#8211; the effect of Seroquel on the sleep cycle in depressed people. <\/p>\n<div align=\"justify\">I could only access two of the three positive studies of Seroquel XR&reg; in Major Depressive Disorder done by the Moonstone Study Group used in Trivedi et al&#8217;s analysis. Here are the published responses of the changes in MADRS scores in those two studies:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/www.cnsspectrums.com\/userdocs\/articleimages\/166\/0609CNS_Weisler.pdf\">Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study.<\/a><\/div>\n<div align=\"center\" class=\"small\">by Weisler R, Joyce M, McGill L, Lazarus A, Szamosi J, and Eriksson H<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">CNS Spectrums<\/font><\/strong>. 2009 14:299&ndash;313.<\/div>\n<div align=\"center\" class=\"middle\">[<a target=\"_blank\" href=\"http:\/\/www.cnsspectrums.com\/userdocs\/articleimages\/166\/0609CNS_Weisler.pdf\">full text on-line<\/a>]<\/div>\n<div align=\"center\"><img decoding=\"async\" height=\"275\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/seroquel-xr-16.gif\" \/><\/div>\n<\/blockquote>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20691481\" target=\"_blank\">Efficacy and tolerability of extended release quetiapine fumarate [quetiapine XR monotherapy in major depressive disorder: a placebo-controlled, randomized study.<\/a><\/div>\n<div align=\"center\" class=\"small\">by Bortnick B, El-Khalili N, Banov M, Adson D, Datto C, Raines S, Earley W, and Eriksson H<\/div>\n<div align=\"center\" class=\"middle\"> <strong><font color=\"#200020\">Journal of Affective Disorders<\/font><\/strong>. 2011 128:83&ndash;94.<\/div>\n<p>             <\/p>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"281\" height=\"275\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/seroquel-xr-15.gif\" \/><\/div>\n<\/blockquote>\n<p align=\"justify\">They get better fast on Seroquel XR&reg;, but they don&#8217;t get that much better &#8211; two to three points on the MADRS Scale over placebo. Now here&#8217;s what Trivedi et al reported measuring only the sleep items of the MADRS Scale in the pooled data:<\/p>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23673347\" target=\"_blank\">Evaluation   of the effects of extended release quetiapine fumarate monotherapy on   sleep disturbance in patients with major depressive disorder: a pooled   analysis of four randomized acute studies.<\/a> <\/div>\n<div align=\"center\" class=\"small\">by Trivedi MH, Bandelow B, Demyttenaere K, Papakosts GI, Szamosi J, Earley W, and Eriksson H.<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">International Journal of Neuropsychopharmacology<\/font><\/strong>. 2013 14:1-12.<\/div>\n<div align=\"center\"><img decoding=\"async\" height=\"275\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/seroquel-xr-17.gif\" \/><\/div>\n<\/blockquote>\n<div align=\"justify\">So, if you pulled out the sleeping pill effect of Seroquel XR&reg;, I expect that the overall scores wouldn&#8217;t look very good, like there goes the significance. I can&#8217;t do those numbers because I don&#8217;t have the raw data [because more people need to sign the <a href=\"http:\/\/www.alltrials.net\/\" target=\"_blank\"><strong><font color=\"#990000\">AllTrials<\/font><\/strong><\/a> petition]. Suffice it to say that perhaps Seroquel XR&reg; has no antidepressant properties at all but rather is helping people and changing scores in MDD because it&#8217;s a potent sedative. That&#8217;s what I think, but I wanted to explore that further &#8211; to see the MDRS plots for the pooled data, but they weren&#8217;t in Trivedi et al. The only thing was the MADRS Scores fractionated by sleep history:<\/div>\n<p align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"177\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/seroquel-xr-18.gif\" \/><\/p>\n<div align=\"justify\">I felt pretty good about my conclusion, but I was annoyed that I couldn&#8217;t do what I wanted to do &#8211; subtract the sleep difference and see what was left in the MADRS depression score for the pooled data. Then I remembered there was another study where they pooled all four earlier studies &#8211; another Trivedi at that:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23485955\" target=\"_blank\">Quetiapine  XR monotherapy in major depressive disorder: a pooled analysis to  assess the influence of baseline severity on efficacy<\/a><\/div>\n<div align=\"center\" class=\"small\">by Thase ME, Montgomery S, Papakostas GI, Bauer M, Trivedi MH, Sveds&auml;ter H, Locklear JC, Gustafsson U, Datto C, Eriksson H.<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">International Clinical Psychopharmacology<\/font><\/strong>. 2013 28[3]:113-20.   <\/div>\n<p>    <\/p>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"379\" height=\"275\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/seroquel-xr-19.gif\" \/><\/div>\n<\/blockquote>\n<div align=\"justify\">Foiled again. But it was sort of there. This was a study that proposed to look at the severity of depression and see if covaried with Seroquel XR&reg; responses &#8211; and it didn&#8217;t. The difference in MADRS scores was the same no matter how depressed you were. But from that plot, I could see that the mean difference was right at three points with a pretty broad confidence interval. I decided that the writers at Complete Medical Communications didn&#8217;t show the MADRS plot for the pooled studies because they didn&#8217;t want some yokel like me coming along and claiming that Seroquel XR&reg; had no antidepressant properties &#8211; that it was just a sleeping pill. But some yokels are persistent:<\/div>\n<ol>\n<li>\n<div align=\"justify\">There was no dose response curve with varying doses of Seroquel XR&reg;.<\/div>\n<\/li>\n<li>\n<div align=\"justify\">The severity of the baseline depression didn&#8217;t effect the response.<\/div>\n<\/li>\n<li>\n<div align=\"justify\">The MADRS response in people with little sleep problem was not significant.<\/div>\n<\/li>\n<li>\n<div align=\"justify\">The fall in MADRS scores was immediate and paralleled the sleep improvement.<\/div>\n<\/li>\n<li>\n<div align=\"justify\">The MADRS placebo\/drug difference was small and would likely be insignificant without the sleep parameters.<\/div>\n<\/li>\n<\/ol>\n<div align=\"justify\">I rest my case. Seroquel XR&reg; is a sleeping pill, not an antidepressant &#8211; an effective sleeping pill that&#8217;s expensive in more ways than one and becomes a new Albatross to deal with&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Oh sleep! it is a gentle thing, Beloved from pole to pole! To Mary Queen the praise be given! She sent the gentle sleep from Heaven, That slid into my soul. The Rime Of The Ancient Mariner by by Samuel Taylor Coleridge Sleep disturbance is a much complained of symptom among the depressed, from the [&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_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-37872","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/37872","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=37872"}],"version-history":[{"count":49,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/37872\/revisions"}],"predecessor-version":[{"id":37921,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/37872\/revisions\/37921"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=37872"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=37872"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=37872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}