{"id":8481,"date":"2011-05-05T13:21:03","date_gmt":"2011-05-05T17:21:03","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=8481"},"modified":"2011-05-06T05:49:15","modified_gmt":"2011-05-06T09:49:15","slug":"godzilla-vs-ghidorah-the-three-headed-monster-from-outer-space","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/05\/05\/godzilla-vs-ghidorah-the-three-headed-monster-from-outer-space\/","title":{"rendered":"Godzilla vs. Ghidorah [the Three Headed Monster from Outer Space]<\/sub>…"},"content":{"rendered":"\n

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circa 1964<\/sup><\/div>\n

\"GodzillaOkay, so my Japanese filmography is a little off. The first Godzilla versus<\/em> movie pitted Godzilla against King Kong [right]. I just couldn’t resist the Godzilla vs. Ghidorah the Three Headed Monster from Outer Space visual to describe the coming face off over the fate of personalized medicine in psychiatry between Evian Gordon’s Brain Resources<\/font><\/strong> and Madhukar Trivedi’s NIMH<\/font><\/strong> funded offering. While there a number of differences between these studies, the thrust of things is similar – treat different groups of depressed people with different antidepressants, then measure everything that can be conceivably be measured.<\/p>\n

The obvious point of both studies is to sift through the masses of data and locate objective measures that will predict success with a specific treatment.  Both studies are commanded by veterans of STAR*D<\/font><\/strong> and CO-MED<\/font><\/strong>, previous attempts to find ways to improve the results of the antidepressants. My own take on STAR*D<\/font><\/strong> and CO-MED <\/font><\/strong>has been more than adequately documented here. The studies accepted a loosely collected cohort, used idiosyncratic outcome measures including an unproven [and apparently widely unused] telephone call-in psychometric, and then they competed for honors in data obfuscation. Neither produced any enduring clarification of drug treatment of MDD. R\u00c3\u00a9sum\u00c3\u00a9 expansion was the major outcome as best I could tell.<\/p>\n

iSPOT<\/font><\/strong> is already underway [clinical trial<\/strong><\/a><\/u>, intro article<\/strong><\/u><\/a>].  They plan 2016 MDD patients from a variety of sites [primary care, specialty, academic, private] divided into three groups treated with Escitalopram [Lexapro], Sertraline [Zoloft], or Venlafaxine XR [Effexor]. There is no placebo group. The data followed has been previously discussed here<\/strong><\/u><\/a> and is available in their article<\/u><\/strong><\/a> [includes Brain Resource<\/font><\/strong>‘s proprietary instruments]:<\/div>\n
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International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol<\/a><\/strong><\/u>
by Leanne M Williams, A John Rush, Stephen H Koslow, Stephen R Wisniewski, Nicholas J Cooper, Charles B Nemeroff, Alan F Schatzberg, and Evian Gordon<\/sup>
Trials<\/strong>. <\/span>2011; <\/span>12<\/span>: 4.<\/span> <\/div>\n

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Background<\/strong>: Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators.<\/sup><\/div>\n
Methods\/Design<\/strong>: The International Study to Predict Optimized Treatment – in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm.<\/sup><\/div>\n
Discussion<\/strong>: First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide.<\/sup><\/div>\n<\/blockquote>\n

Trivedi’s NIMH<\/font><\/strong> funded study is not yet off the ground [no clinical trial registered that I can find.] The only write-up I’ve found is the NIMH description [the race for biomarkers…<\/strong><\/u><\/a>]. There’s no placebo group. They plan for 675 subjects divided among citalopram [Celexa], bupropion [Wellbutrin], and cognitive behavioral therapy [CBT]. The testing is not so clearly described as with iSPOT<\/font><\/strong>.<\/p>\n\n\n\n\n\n
Project Number:<\/strong> <\/td>\n \t\t\t\t\t \t\t\t\t\t1U01MH092221-01<\/strong><\/u><\/a> \t\t\t\t\t \t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t<\/td>\n \t\t\t\t\t\t\t\t\t\t\t\t\tContact Principal Investigator:<\/strong><\/td>\n \t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\tTRIVEDI, MADHUKAR H\t \t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t<\/td>\n<\/tr>\n
\t\t\t\t\t\t\t\t\t\t\t\t\tTitle:<\/strong><\/td>\n \t\t\t\t\t\t\t\t\t\t\t\t\t\tESTABLISHING MODERATORS\/BIOSIGNATURES OF ANTIDEPRESSANT RESPONSE- CLINICAL CARE \t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t<\/td>\n \t\t\t\t\t\t\t\t\t\t\t\t\tAwardee Organization:<\/strong><\/td>\n \t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\tUNIVERSITY OF TEXAS SW MED CTR\/DALLAS \t\t\t\t\t\t\t\t\t\t\t\t\t<\/td>\n<\/tr>\n
Abstract Text:<\/strong><\/td>\n<\/tr>\n
\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t DESCRIPTION (provided by applicant): The timely selection of the best treatment for patients with depression is critical to the goal of improving remission rates. Due to the biological heterogeneity and variable symptom presentation of depression, it is unlikely that a single clinical or biological marker can guide treatment selection. Rather, a biosignature developed from a systematic exploration of a group of clinical and biological markers is more likely to be successful. Two types of biosignatures are needed to achieve improved outcomes: 1) biosignatures to maximize the selection of optimal treatment for individual patients at the beginning of treatment (moderators) and 2) biosignatures to identify indicators of eventual outcomes early in treatment (mediators). This approach has great potential to personalize treatment and maximize the number of patients who can be treated to full remission with a given treatment. 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, & gender) and biological (i.e. genetic, neuroimaging, serum, epigenetic & 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… <\/sup> \t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t <\/td>\n<\/tr>\n<\/table>\n

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While my personal skepticism about these enterprises knows no bounds [in no particular order]:<\/div>\n