{"id":6788,"date":"2011-04-03T16:31:29","date_gmt":"2011-04-03T20:31:29","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=6788"},"modified":"2013-05-31T11:27:40","modified_gmt":"2013-05-31T15:27:40","slug":"a-thirty-five-million-dollar-misunderstanding","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/04\/03\/a-thirty-five-million-dollar-misunderstanding\/","title":{"rendered":"a thirty-five million dollar misunderstanding&#8230;"},"content":{"rendered":"<div align=\"justify\">When I started in Psychiatry, if someone said they were going to do a study treating 4041 depressed patients [confirmed by their scores on a rating scale] using a set of sequenced treatment alternatives to relieve depression, I would have had a blank look, because then, depression wasn&#8217;t an entity. It was an emotion, an aspect of human experience, a signal from the interior. As a symptom, depression had an almost unending differential diagnosis [including a few who had Depression that did appear to be an &#8216;entity&#8217;]. And if I then read the opening lines of a paper about those sequenced treatment alternatives to relieve depression that started like this:                               <\/div>\n<ul>\n<div align=\"justify\"><sup>Symptom remission is the desired goal of treatment for depression, given its implications for better daily functioning and better longer-term prognosis. Since no treatment is a panacea, several sequential treatment steps are often needed to obtain remission with a tolerated treatment. If a trial does not result in remission, it is an unsuccessful trial, whether due to lack of efficacy or intolerable side effects, as long as the treatment is vigorously dosed to tolerance and provided for a sufficient duration to achieve remission. The number of treatment steps needed to achieve an adequate benefit is typically used to gauge the degree of treatment resistance, usually with a focus on acute outcomes without reference to longer-term outcomes.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">I&#8217;d get hung up at the first sentence, &quot;<em>Symptom remission is the desired goal of treatment for depression, given  its implications for better daily functioning and better longer-term  prognosis<\/em>.&quot; That sentence says that the depression is interfering with their lives, and I would want to say, &quot;What about the people whose lives are the reason they&#8217;re depressed?&quot; I&#8217;d have trouble with all the other sentences too, but I don&#8217;t want to go on and on. If you then told me that the conclusion of the study said:<\/div>\n<ul>\n<div align=\"justify\"><sup>After two treatment steps, it appears that over 50% of patients will achieve remission if they stay in treatment (i.e., 36.8% step 1 plus 30.6% of the remaining 63.2% of patients). Thereafter, the chances of subsequent remission  are much lower. The theoretical cumulative remission rate after four acute treatment steps was 67%.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">I would&#8217;ve said, &quot;I don&#8217;t believe that&#8217;s right.&quot; I wouldn&#8217;t have known what else to say.<\/div>\n<blockquote>\n<div align=\"center\"><strong><a href=\"http:\/\/ajp.psychiatryonline.org\/article.aspx?articleID=97282\" target=\"_blank\">Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.<\/a><\/strong><br \/>                                       by  Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart  JW, Warden  D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath  PJ, Rosenbaum  JF, Sackeim HA, Kupfer DJ, Luther J, Fava M.<br \/>                                      <strong>Am J Psychiatry<\/strong>. 2006 Nov;163(11):1905-17.<\/div>\n<div><em><strong>Abstract<\/strong><\/em><\/div>\n<div align=\"justify\"><sup><strong><u>OBJECTIVE<\/u>:<\/strong>   This  report describes the participants and compares the acute and    longer-term treatment outcomes associated with each of four successive    steps in the Sequenced Treatment Alternatives to Relieve Depression    (STAR*D) trial.<\/sup><\/div>\n<div align=\"justify\"><sup><strong><u>METHOD<\/u>:<\/strong>  A  broadly  representative adult outpatient sample with nonpsychotic  major   depressive disorder received one (N=3,671) to four (N=123)  successive   acute treatment steps. Those not achieving remission with or  unable to   tolerate a treatment step were encouraged to move to the  next step.   Those with an acceptable benefit, preferably symptom  remission, from  any  particular step could enter a 12-month naturalistic  follow-up  phase. A  score of &lt;or=5 on the Quick Inventory of  Depressive   Symptomatology-Self-Report (QIDS-SR(16)) (equivalent to  &lt;or=7 on the   17-item Hamilton Rating Scale for Depression  [HRSD(17)]) defined   remission; a QIDS-SR(16) total score of &gt;or=11  (HRSD(17)&gt;or=14)   defined relapse.<\/sup><\/div>\n<div align=\"justify\"><sup><strong><u>RESULTS<\/u>:<\/strong>  The  QIDS-SR(16)  remission rates were 36.8%, 30.6%, 13.7%, and 13.0%  for the  first,  second, third, and fourth acute treatment steps,  respectively.  The  overall cumulative remission rate was 67%.  Overall, those who  required  more treatment steps had higher relapse  rates during the  naturalistic  follow-up phase. In addition, lower  relapse rates were  found among  participants who were in remission at  follow-up entry than  for those  who were not after the first three  treatment steps.<\/sup><\/div>\n<div align=\"justify\"><sup><strong><u>CONCLUSIONS<\/u>:<\/strong>  When   more treatment steps are required, lower acute remission rates    (especially in the third and fourth treatment steps) and higher relapse    rates during the follow-up phase are to be expected. Studies  to  identify  the best multistep treatment sequences for individual   patients and the  development of more broadly effective treatments are   needed.<\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">Here&#8217;s the flow  chart from that study:<\/div>\n<div align=\"center\"><img decoding=\"async\" vspace=\"5\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/star-d-1.gif\" \/><\/div>\n<div align=\"justify\"><img loading=\"lazy\" decoding=\"async\" width=\"200\" hspace=\"4\" height=\"216\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/star-d-2.gif\" \/>If  this is your first time with the STAR*D  trial, it&#8217;s unlikely that this  flow-chart is very clarifying, so I&#8217;ve  simplified the chart on the  right for our perusal, removing the details. In this trial &quot;Exit&quot; means   drop-out. After each level of treatment, some number of subjects elect   to stop. That group is designated as &quot;Follow-Up&quot; but only a portion of   those are in remission [the numbers in gray and green come from Table 3   in the article]. So the 67% is a hypothetical wish in virtual reality,  not what the study actually demonstrated. And what of the drop-outs  [38% of the subjects  who entered some form of treatment dropped out]?  In the paper, the authors say:<\/div>\n<ul>\n<div align=\"justify\"><sup>The   cumulative remission rate can be estimated by assuming that 100   patients begin citalopram treatment. Overall, 36.8 will achieve   remission in step 1, leaving 63 to proceed to the next step. In step 2,   30.6% (N=19) will remit (.306&times;63 = 19). In the third step, 13.7% or N=6   will remit (.137 x [100&ndash;37-19]). In the fourth step, 13.0% or N=5 will   remit. The theoretical cumulative remission rate is 67% (37+19+6+5).   Note that this estimate assumes no dropouts, and it assumes that those   who exited the study would have had the same remission rates as those   who stayed in the protocol.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">First off, the numbers at the various levels vary depending on where you  look in the paper. The ones I&#8217;ve displayed are close, but not  guaranteed. Second, I can&#8217;t come up with those remission rates [36.8%,  30.6%, 13.7%, and 13.0%]. I&#8217;m sure they came from some computation, but I  can&#8217;t figure out what it was. Here&#8217;s how the numbers work out as best I can gather them:<\/div>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"447\" vspace=\"5\" height=\"114\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/star-d-3.gif\" \/><\/div>\n<div align=\"justify\">If I use the number that didn&#8217;t drop out [3671 &#8211; 1427 =&nbsp; 2244], I can get close to what they hypothesize [1516\/2244 = <strong>67%<\/strong>]. Since their assumption is absurd [&quot;<em>&#8230; assumes that those   who exited the study would have had the same remission rates as those   who stayed in the protocol<\/em>&quot;], I calculated <strong>41%<\/strong> [1516\/3671 = 41%] considering them as treatment failures. I don&#8217;t believe that number either [too high], but for the moment I&#8217;d ask why didn&#8217;t they report, &quot;<em>the cumulative remission rate was between 41% and 67%<\/em>&quot; to reflect the best and worst case scenarios from their study?                  <\/div>\n<p>               <\/p>\n<div align=\"justify\">If you think I&#8217;m being too harsh to consider that the people who dropped out of the STAR*D trial were treatment failures, I&#8217;m just taking them at their word, &quot;<em>If a trial does not result in remission, it is an unsuccessful trial,  whether due to lack of efficacy or intolerable side effects, as long as  the treatment is vigorously dosed to tolerance and provided for a  sufficient duration to achieve remission<\/em>&quot; [ignoring the moralizing at the end]. But you ain&#8217;t heard nothing yet. Others have been over this study with a fine tooth comb and found more than enough to write about. <strong>Robert Whitaker<\/strong>, author of <u><a target=\"_blank\" href=\"http:\/\/www.amazon.com\/Anatomy-Epidemic-Bullets-Psychiatric-Astonishing\/dp\/0307452417\"><strong><font color=\"#300030\">Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America<\/font><\/strong><\/a><\/u>, summarizes their findings in <a target=\"_blank\" href=\"http:\/\/www.psychologytoday.com\/blog\/mad-in-america\/201008\/the-stard-scandal-new-paper-sums-it-all\"><u><strong><font color=\"#300030\">The STAR*D Scandal: A New Paper Sums It All Up<\/font><\/strong><\/u><\/a> [the new paper being <u><a target=\"_blank\" href=\"http:\/\/content.karger.com\/ProdukteDB\/produkte.asp?Aktion=ShowPDF&#038;ArtikelNr=318293&#038;Ausgabe=254424&#038;ProduktNr=223864&#038;filename=318293.pdf\"><strong><font color=\"#300030\">Efficacy and Effectiveness of Antidepressants: Current Status of Research<\/font><\/strong><\/a><\/u>]. Whitaker&#8217;s book, article, and the &quot;new paper&quot; all deserve to be read in the original, but for the moment take a look at what Whitaker summarizes in his article:<\/div>\n<ul>\n<div align=\"justify\"><sup>1. The STAR*D investigators reported a &quot;cumulative&quot; remission rate of 67%  in the abstract of an article, when in fact this was simply a  &quot;theoretical&quot; rate.<\/sup><\/div>\n<div align=\"justify\"><sup>2. They reported remission rates based on the  QIDS-SR scale, even though the pre-specified primary outcome scale was  the HRSD, and this switch inflated the remission numbers.<\/sup><\/div>\n<div align=\"justify\"><sup>3. They  included remission numbers for patients who weren&#8217;t depressed enough at  baseline to meet study criteria, and thus weren&#8217;t eligible for analysis.<\/sup><\/div>\n<div align=\"justify\"><sup>4. They reported that 33.3% to 50% of remitted patients relapsed  during the 12-year followup, which suggested &#8211; when combined with the  inflated 67% remitted rate &#8211; that perhaps 40% of all patients who  entered the trial had recovered and stayed well, when in fact only 3% of  the entering patients had a &quot;sustained remission&quot; [and stayed in the  trial].<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">To be honest, these assessments seemed too harsh to me too &#8211; but they aren&#8217;t. For example, number 2. [changing rating scales in mid-stream] is easy to check out. The <a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT00021528?term=star*d&#038;rank=3\"><u><strong><font color=\"#300030\">STAR*D Clinical Trial<\/font><\/strong><\/u><\/a> is posted online and a perusal of the <a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\/archive\/NCT00021528\"><u><strong><font color=\"#300030\">history of changes<\/font><\/strong><\/u><\/a> confirms this conclusion just as it is reported. Chasing down numbers 3. and 4. are equally possible, and I couldn&#8217;t find anything to question in their conclusions [In fact, I thought the article, <strong><font><u><a target=\"_blank\" href=\"http:\/\/content.karger.com\/ProdukteDB\/produkte.asp?Aktion=ShowPDF&#038;ArtikelNr=318293&#038;Ausgabe=254424&#038;ProduktNr=223864&#038;filename=318293.pdf\"><strong><font color=\"#300030\">Efficacy and Effectiveness of Antidepressants: Current Status of Research<\/font><\/strong><\/a><\/u><\/font><\/strong> by Pigott, Allan, Leventhal, Alter and Boren from the Department of Psychology at American University, was exemplary, and, if anything, too soft on the STAR*D, authors considering all the things they found]. There&#8217;s more from Dr. Pigott on STAR*D <a target=\"_blank\" href=\"http:\/\/www.madinamerica.com\/madinamerica.com\/Pigott.html\"><u><strong><font color=\"#200020\">here<\/font><\/strong><\/u><\/a>.<\/div>\n<p>                     <\/p>\n<table width=\"95%\" cellspacing=\"0\" cellpadding=\"2\" border=\"0\" align=\"center\">\n<tr>\n<td>\n<div align=\"justify\">Before responding with my own thoughts about this study, I have to mention this part:           <\/div>\n<ul>\n<div align=\"justify\"><sup>The <strong><font color=\"#300030\">interactive voice response system<\/font><\/strong> collected measures of functioning and quality of life at baseline, 6 weeks, and exit from each acute treatment trial and at monthly intervals during the 12- month naturalistic follow-up phase. Interactive voice response ratings included physical and mental health functioning assessed with the 12-item Short Form Health Survey (SF-12), the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire, and the 5-item Work and Social Adjustment Scale. During the 12-month naturalistic follow-up phase, the interactive voice response also collected monthly QIDS-SR16 scores. The QIDS-SR16 total scores obtained through the interactive voice response system correspond very closely to both the paper-and-pencil QIDS-SR16 and the QIDS-C16.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">I find using an <strong><font color=\"#300030\">interactive voice response system<\/font><\/strong> to collect data and rating scales [in fact anything] from patients insulting. They spent $35M of the government&#8217;s money and they did their follow-up with one of those annoying phone systems? I&#8217;m trying to make nice, but I can&#8217;t bring it off with this part. &quot;Press three if you are feeling&#8230;?&quot; Give us a break!<\/div>\n<\/td>\n<\/tr>\n<\/table>\n<h1 align=\"center\">What I think about STAR*D<\/h1>\n<p align=\"justify\">I&#8217;m not an anti-psychiatrist. I&#8217;m a psychiatrist and have prescribed many [but not all] of the drugs mentioned in this study. But I didn&#8217;t review the study for this last week or so because I believed what it said or to learn anything about treating depressed people. Nobody who uses these medications and actually sees patients could possibly believe those conclusions. I read it to collect my thoughts about the psychiatrists who wrote it and the government agency that funded it. One of my conclusions was easy &#8211; these authors are anti-psychiatrists. Who needs a psychiatrist to collect a list of symptoms, conclude that the person is depressed from that list, then plug the depressed person into an algorithmic protocol like the one they describe? I&#8217;m not even sure you would need a doctor or trained mental health professional. An overqualified <strong><font color=\"#003399\">Walmart<\/font><\/strong> greeter I met recently could do that quite well.<\/p>\n<p align=\"justify\">As an Internist, I saw lots of depressed people. I didn&#8217;t follow the path suggested here even back then. I learned to ask those patients about their lives, their relationships, their experiences. But I didn&#8217;t have to ask very much. Just asking anything at all got them started talking and I learned a lot about why they were depressed, but I didn&#8217;t know what to do with what I learned &#8211; and I wanted to. So I came back and did a Psychiatry Residency to find out what to do, fortunately in the pre-STAR*D days. Had the notions in this study been the curriculum, I would have happily returned to Internal Medicine. Instead, I learned that depression was a human emotion we can all experience. I learned that sometimes, it can be a disease, like in Manic Depressive Illness, or Post-Partum Depression, or when you take certain medicines, etc. But most of the time, it&#8217;s a starting place to signal that it&#8217;s time to start untying some of those knots that experience has a way of tying in our lives and minds. And that&#8217;s what I did for thirty years, learn to help people with the untying. It&#8217;s what I wanted to learn back in the Internist days and it was worth the trip.<\/p>\n<p align=\"justify\">I gave [and give] the medications. For a few, they&#8217;re a godsend. For others, they help to a varying degree. But I never conceived this &#8211; &quot;<em>Symptom remission is the desired goal of treatment for depression, given  its implications for better daily functioning and better longer-term  prognosis.<\/em>&quot; That would mean that feeling depressed was outside the spectrum of human experience, that it said nothing about the life of the person &#8211; an alien emotion to be excised. I didn&#8217;t believe that as an Internist, and I don&#8217;t believe it now. I personally find the whole thrust of this way of looking at people strange. It&#8217;s like treating someone with a severe headache with analgesics before finding out if they have Migraine, or a brain tumor, or are having a stroke, or a million other things. I agree that there are people with depression that do have a pathological mood state independent of life\/mind things. I used to treat them too when I was up on things. Now, when I see them, I send them to friends who are in the business of treating such cases, who see them all the time. But there aren&#8217;t so many in that category.<\/p>\n<p align=\"justify\">In other posts, I&#8217;ve talked about the sorry state of the Clinical Research&nbsp; Industry and the heavy bias in the Pharmaceutical Industry&#8217;s Clinical Trials [the ones Dr. Bernard Carroll calls &quot;experimercials&quot;]. But this study is different with its generous NIMH funding. I&#8217;ll even forgo my usual suspicions that the subjects really didn&#8217;t really fit the bill diagnostically. But even at that, this study was &quot;fudged&quot; all over the place. The question is why? None of the authors was in the pocket of some drug company whose favorite drug was featured, and yet the whole study reeks of bias. How come? What is the bias of these authors [whom I presume designed this study themselves]?<\/p>\n<div align=\"justify\">They seem to have a belief system:<\/div>\n<ul>\n<li>\n<div align=\"justify\">Depression, whether it&#8217;s a disease or an emotion, is a bad thing&nbsp; and the point is to make it go away with some form of treatment, usually drugs [&quot;<em>Symptom remission is the desired goal of treatment for depression, given its implications for better daily functioning and better longer-term prognosis<\/em>&quot;].<\/div>\n<\/li>\n<li>\n<div align=\"justify\">If the treatment doesn&#8217;t make it go away, the subject has something called treatment resistance, and should try another treatment [&quot;<em>The number of treatment steps needed to achieve an adequate benefit is typically used to gauge the degree of treatment resistance&#8230;<\/em>&quot;].<\/div>\n<\/li>\n<li>\n<div align=\"justify\">The goal of Psychiatry is to&nbsp; improve on this treatment scheme [&quot;<em>Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed<\/em>&quot;].<\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\">So one bias in these authors that might explain why they were invested in making this study look better than it was would be to confirm and affirm this idiosyncratic belief system. There&#8217;s another related possibility:<\/div>\n<ul>\n<div align=\"justify\"><u>Dr. Rush<\/u> has served as an advisor, consultant, or speaker for or received research support from Advanced Neuromodulation Systems, Inc.; Best Practice Project Management, Inc.; Bristol-Myers Squibb Company; Cyberonics, Inc.; Eli Lilly &amp; Company; Forest Pharmaceuticals, Inc.; Gerson Lehman Group; GlaxoSmithKline; Healthcare Technology Systems, Inc.; Jazz Pharmaceuticals; Merck &amp; Co., Inc.; the National Institute of Mental Health; Neuronetics; Ono Pharmaceutical; Organon USA Inc.; Personality Disorder Research Corp.; Pfizer Inc.; the Robert Wood Johnson Foundation; the Stanley Medical Research Institute; the Urban Institute; and Wyeth-Ayerst Laboratories Inc. He has equity holdings in Pfizer Inc and receives royalty\/patent income from Guilford Publications and Healthcare Technology Systems, Inc.<\/div>\n<div align=\"justify\"><u>Dr. Trivedi<\/u> has served as an advisor, consultant, or speaker for or received research support from Abbott Laboratories, Inc.; Akzo (Organon Pharmaceuticals Inc.); Bayer; Bristol-Myers Squibb Company; Cephalon, Inc.; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Eli Lilly &amp; Company; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica; Johnson &amp; Johnson PRD; Meade Johnson; the National Institute of Mental Health; the National Alliance for Research in Schizophrenia and Depression; Novartis; Parke-Davis Pharmaceuticals, Inc.; Pfizer Inc; Pharmacia &amp; Upjohn; Predix Pharmaceuticals; Sepracor; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories.<\/div>\n<div align=\"justify\"><u>Dr. Wisniewski<\/u> has received research support from the National Institute of Mental Health and served as an advisor\/consultant for Cyberonics, Inc.<\/div>\n<div align=\"justify\"><u>Dr. Nierenberg<\/u> has served as an advisor, consultant, or speaker for or received research support from Bristol-Myers Squibb Company; Cederroth; Cyberonics, Inc.; Eli Lilly &amp; Company; Forest Pharmaceuticals Inc.; Genaissance; GlaxoSmithKline; Innapharma; Janssen Pharmaceutica; Lichtwer Pharma; the National Institute of Mental Health; the National Alliance for Research in Schizophrenia and Depression; Neuronetics; Organon, Inc.; Pfizer Inc; Sepracor; Shire; Stanley Foundation; and Wyeth-Ayerst Laboratories.       <\/div>\n<div align=\"justify\"><u>Dr. Stewart<\/u> has served as an advisor, consultant, or speaker for or received research support from Eli Lilly &amp; Company; GlaxoSmithKline; Organon USA Inc.; Shire; and Somerset.<\/div>\n<div align=\"justify\"><u>Dr. Warden<\/u> has received research support from the National Institute of Mental Health and has equity holdings in Bristol-Myers Squibb Company and Pfizer, Inc.<\/div>\n<div align=\"justify\"><u>Dr. Thase<\/u> has served as an advisor, consultant, or speaker for AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Eli Lilly &amp; Company; Forest Laboratories, Inc.; GlaxoSmithKline; Janssen Pharmaceutica; Eli Lilly &amp; Company; Novartis; Organon, Inc.; Pfizer Pharmaceutical; Sanofi Aventis; Sepracor, Inc.; Shire US Inc.; and Wyeth Pharmaceuticals.<\/div>\n<div align=\"justify\"><u>Dr. Lavori<\/u> has served as an advisor, consultant, or speaker for or received research support from Bristol-Myers Squibb Company; Celera Diagnostics Inc; Cyberonics, Inc.; the Department of Veterans Affairs; Forest Pharmaceuticals, Inc.; Glaxo-SmithKline; Leaf Cabrezer Hyman and Bernstein; the National Institutes of Health; and Neuronetics, Inc. <\/div>\n<div align=\"justify\"><u>Dr. McGrath<\/u> has served as an advisor, consultant, or speaker for or received research support from Eli Lilly &amp; Company; GlaxoSmithKline; Lipha Pharmaceuticals; the National Institute of Mental Health; the National Institute on Alcohol Abuse and Alcoholism; New York State Department of Mental Hygiene; Organon, Inc.; Research Foundation for Mental Hygiene (New York State); and Somerset Pharmaceuticals. <\/div>\n<div align=\"justify\"><u>Dr. Rosenbaum<\/u> has served as an advisor, consultant, or speaker for or received research support from Astra-Zeneca; Boehringer-Ingelheim; Bristol-Myers Squibb Company; Cephalon; Compellis; Cyberonics; EPIX; Forest; GlaxoSmithKline; Janssen; Lilly; MedAvante; Neuronetics; Novartis; Orexigen; Organon; Pfizer, Inc; Roche Diagnostics; Sanofi; Schwartz; Somaxon; Somerset; Sepracor; Shire; Supernus; and Wyeth. He has equity holdings in Compellis, Medavante, and Somaxon. <\/div>\n<div align=\"justify\"><u>Dr. Sackeim<\/u> has served as an advisor, consultant, or speaker for or received research support from Cyberonics, Inc.; Eli Lilly &amp; Company; Magstim Ltd.; MECTA Corporation; Neurocrine Biosciences Inc.; Neuronetics Inc.; NeuroPace Inc.; and Pfizer Inc. <\/div>\n<div align=\"justify\"><u>Dr. Kupfer<\/u> has served as an advisor, consultant, or speaker for or received research support from Amersham; the Commonwealth of Pennsylvania; Corcept Corporated; Eli Lilly &amp; Company; F. Hoffmann-La Roche Ltd.; Forest Pharmaceuticals; Lundbeck; the National Institute of Mental Health; Novartis; Pfizer, Inc; Servier Amerique; and Solvay\/Wyeth. He has equity holdings in B<u><img decoding=\"async\" width=\"180\" hspace=\"4\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/star-d-4.gif\" \/><\/u>ody Media and Med Avante and receives royalty income from Oxford University Press. <\/div>\n<div align=\"justify\"><u>Dr. Fava<\/u> has served as an advisor, consultant, or speaker for or received research support from Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bayer AG; Biovail Pharmaceuticals, Inc.; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; Eli Lilly &amp; Company; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Grunenthal GmBH; J &amp; J Pharmaceuticals; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Company; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck; MedAvante, Inc.; Novartis; Nutrition 21; Organon Inc.; PamLab, LLC; Pfizer, Inc; PharmaStar; Pharmavite; Roche; Sanofi\/Synthelabo; Sepracor; Solvay Pharmaceuticals, Inc.; Somerset Pharmaceuticals; and Wyeth-Ayerst Laboratories. He has equity holdings in Compellis and MedAvante. <\/div>\n<div align=\"justify\"><u>Dr. Niederehe<\/u>, <u>Dr. Lebowitz<\/u>, and <u>Mr. Luther<\/u> report no competing interests.<\/div>\n<\/ul>\n<div>Pitiful!&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>When I started in Psychiatry, if someone said they were going to do a study treating 4041 depressed patients [confirmed by their scores on a rating scale] using a set of sequenced treatment alternatives to relieve depression, I would have had a blank look, because then, depression wasn&#8217;t an entity. It was an emotion, an [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","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":[5],"tags":[],"class_list":["post-6788","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/6788","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=6788"}],"version-history":[{"count":49,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/6788\/revisions"}],"predecessor-version":[{"id":36961,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/6788\/revisions\/36961"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=6788"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=6788"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=6788"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}