{"id":20699,"date":"2012-03-07T08:00:15","date_gmt":"2012-03-07T13:00:15","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=20699"},"modified":"2012-03-07T11:46:09","modified_gmt":"2012-03-07T16:46:09","slug":"come-rest-a-while-iii-the-finale","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/03\/07\/come-rest-a-while-iii-the-finale\/","title":{"rendered":"come rest a while III &#8211; <em>the finale<\/em>&#8230;"},"content":{"rendered":"<div align=\"justify\">I keep apologizing for being tedious and obsessed about these two articles published online in the <strong><font color=\"#0066cc\">Archives of General Psychiatry<\/font><\/strong>:<\/div>\n<ul>\n<div align=\"justify\">&bull; <a href=\"http:\/\/archpsyc.ama-assn.org\/cgi\/content\/abstract\/archgenpsychiatry.2011.2048\" target=\"_blank\"><u><strong><font color=\"#200020\">Suicidal Thoughts and Behavior With Antidepressant Treatment<\/font><\/strong><\/u><\/a> [Feb 6]<\/div>\n<div align=\"justify\">&bull; <u><strong><a href=\"http:\/\/archpsyc.ama-assn.org\/cgi\/content\/abstract\/archgenpsychiatry.2011.2044v1\" target=\"_blank\"><font color=\"200020\">Benefits From Antidepressants<\/font><\/a><\/strong><\/u> [March 5]<\/div>\n<\/ul>\n<div align=\"justify\">My apologies are ingenuous. I guess I keep apologizing because I know it&#8217;s just plain boring. I doubt that anyone reading this blog really believes Dr. Gibbons et al&#8217;s assertion that the whole black box warning on antidepressants about youth suicides in 2004 was wrong &#8211; some kind of over-reaction by the FDA. If you&#8217;re a person who sees depressed kids [a psychiatrist or other mental health worker], I doubt that you think SSRIs are particularly effective in kids who are depressed, particularly mildly depressed. And if you&#8217;ve kept up with this business, you are probably suspicious of Dr. Gibbons&#8217; objectivity on this issue in that he&#8217;s spent the last eight years trying to find a way to debunk the black box warning using several different methods, including jumping on the small blip in adolescent suicides in the year the warning was issued &#8211; a blip that disappeared the following year and thereafter. And if you read either of these articles, you know that they contain almost no data, and the descriptions of the methodology and statistical analyses are beyond the reach of any psychiatrist I&#8217;ve even met. But even if they were understandable, it would be impossible to check things because the information just isn&#8217;t around to look at. But if you&#8217;re reading this blog, you&#8217;re an unusual person in that it means you care about the publication of misleading articles in our literature. Most people don&#8217;t give that a lot of thought. They&#8217;re much more likely to read these conclusions in the abstracts, or even more likely be handed or shown a copy by drug reps visiting doctors offices:<\/div>\n<ol>\n<div align=\"justify\"><sup><strong><u>Conclusions<\/u>:&nbsp;<\/strong>  Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for  adult and geriatric patients. This protective effect is mediated by  decreases in depressive symptoms with treatment. For youths, no  significant effects of treatment on suicidal thoughts and behavior were  found, although depression responded to treatment. No evidence of  increased suicide risk was observed in youths receiving active  medication. To our knowledge, this is the first research synthesis of  suicidal thoughts and behavior in depressed patients treated with  antidepressants that examined the mediating role of depressive symptoms  using complete longitudinal person-level data from a large set of  published and unpublished studies.<\/sup><\/div>\n<div align=\"justify\"><sup><strong><u>Conclusions<\/u>:&nbsp;<\/strong>  To our knowledge, this is the first research synthesis in this area to  use complete longitudinal person-level data from a large set of  published and unpublished studies. The results do not support previous  findings that antidepressants show little benefit except for severe  depression. The antidepressants fluoxetine and venlafaxine are  efficacious for major depressive disorder in all age groups, although  more so in youths and adults compared with geriatric patients. Baseline  severity was not significantly related to degree of treatment advantage  over placebo.<\/sup><\/div>\n<\/ol>\n<div align=\"justify\">I don&#8217;t believe either of those things are correct. But worse, I doubt that either of these articles show either of those things. But worst of all, there&#8217;s no possible way to rationally refute those claims because, when it&#8217;s all said and done, there&#8217;s not enough information available either in these articles or elsewhere to even try. These are faith-based articles from people who haven&#8217;t earned the right to have faith bestowed on them. So all I can do is explain why my faith level is so low, and then move on to something that won&#8217;t put people to sleep. So here are a few of my complaints just to get them off my chest.<\/div>\n<p align=\"justify\">My first complaint is about the source of the data. It wasn&#8217;t in the first article [February 6], it was going to be published with the second article [yesterday]. Being impatient, I periodically tried to figure it out to no avail. Along the way, I did learn that the NIMH <strong><font color=\"200020\">Treatment of Adolescents with Depression Study<\/font><\/strong> [TADS] had been deceptively reported, minimizing the suicidality&nbsp; in kids taking Prozac [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2012\/02\/22\/significant-i\"><em><u><strong><font color=\"#200020\">significant<\/font><\/strong><\/u><\/em><u><strong><font color=\"#200020\"> I&hellip;<\/font><\/strong><\/u><\/a>, <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2012\/02\/22\/significant-ii\"><u><strong><font color=\"#200020\"><em>significant<\/em> II&hellip;<\/font><\/strong><\/u><\/a>, <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2012\/02\/23\/significant-iii\"><u><strong><font color=\"#200020\"><em>significant<\/em> III&hellip;<\/font><\/strong><\/u><\/a>]. Even when the second article was published, I couldn&#8217;t find one of the studies until a commenter ran it down and found a clue that lead me to it listed under another drug. That was because everyone in the study was also on Strattera&reg; along with Prozac&reg;. Strattera&reg; is an ADHD medication &#8211; a Selective Norepinephrine Reuptake Inhibitor. In fact, it was a Strattera study, and the patients didn&#8217;t necessarily meet the criteria for Major Depressive Disorder. So I finally located the four studies analyzed by Gibbons et al all to reach the conclusions above about children and adolescents. <\/p>\n<div align=\"justify\">Here they are redrawn to have a uniform <strong><font color=\"#200020\">Children&rsquo;s Depression Rating Scale-Revised [CDRS-R]<\/font><\/strong> full scale display [references in <u><a href=\"http:\/\/1boringoldman.com\/index.php\/2012\/03\/06\/come-rest-a-while-ii\"><strong><font color=\"#200020\">come rest a while II&hellip;<\/font><\/strong><\/a><\/u>]:<\/div>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"384\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/gibbons-3.gif\" \/><\/div>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"384\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/gibbons-4.gif\" \/><\/div>\n<div align=\"justify\">The top two studies [<strong><font color=\"#200020\">X065<\/font><\/strong>, <strong><font color=\"#200020\">HCJE<\/font><\/strong>] were the original ones used to get FDA Approval for children and adolescents [before the black box warning]. TADS was the NIMH study but they didn&#8217;t use the CBT or Prozac+CBT groups, cutting off a a sizable chunk of the <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/images\/vitiello.gif\"><u><strong><font color=\"#200020\">suicidality<\/font><\/strong><\/u><\/a>. For the suicidality analysis, they used the score on the <strong><font color=\"#200020\">CDRS-R<\/font><\/strong> Item 13, a method abandoned by the FDA as inadequate. For efficacy, they only used the first 6 weeks [darkened in]. And Study <strong><font color=\"#200020\">LYAQ<\/font><\/strong> was an inappropriate choice because of admission criteria, the concomitant use of another potent drug, and the low starting <strong><font color=\"#200020\">CDRS-R<\/font><\/strong> scores [they allowed the concomitant Strattera, but not the minimally effective CBT?]. These were all data manipulations bound to affect the outcome. In addition, they selectively quoted the literature eg &quot;The National Institute of Mental Health&ndash;funded STAR*D trial found a 67% remission rate for patients who finished all 4 phases of the trial&quot; [which was a hypothetical, hardly a finding]. Their statistical methods and manipulations were unintelligible, presented as fact without specific methodologies identified or illustrations. The figures and tables were impenetrable. And why was it available full text on-line, then removed? And at least with the child data, why does the reported efficacy of this analysis sound better than any of the four studies used to generate it?<\/div>\n<p> <\/p>\n<div align=\"justify\">This is an important topic &#8211; giving medications carrying a warning of suicidal risk to kids. If someone is going to say that there is no risk and that the medications should be widely used because withholding them is harmful, the evidence should be solid and presented in a way that is accessible to psychiatrists and other physicians reading the material to judge for themselves. This article fails to do that at even a minimal level. It&#8217;s hard for me to imagine that presenting a retrospective analysis like this with this level of obfuscation was not deliberate. And it&#8217;s equally hard for me to imagine that the <strong><font color=\"#0066cc\">Archives of General Psychiatry <\/font><\/strong>would think that their readers would understand [or accept] this kind of presentation. But I&#8217;ve said enough. Time to put it to rest&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>I keep apologizing for being tedious and obsessed about these two articles published online in the Archives of General Psychiatry: &bull; Suicidal Thoughts and Behavior With Antidepressant Treatment [Feb 6] &bull; Benefits From Antidepressants [March 5] My apologies are ingenuous. I guess I keep apologizing because I know it&#8217;s just plain boring. I doubt that [&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-20699","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20699","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=20699"}],"version-history":[{"count":24,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20699\/revisions"}],"predecessor-version":[{"id":20726,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20699\/revisions\/20726"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=20699"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=20699"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=20699"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}