{"id":4695,"date":"2011-02-19T17:38:06","date_gmt":"2011-02-19T22:38:06","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=4695"},"modified":"2011-02-20T13:37:36","modified_gmt":"2011-02-20T18:37:36","slug":"selling-seroquel-iii-the-data-factories","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/02\/19\/selling-seroquel-iii-the-data-factories\/","title":{"rendered":"selling seroquel III: the data factories…"},"content":{"rendered":"\n
\"from<\/a>Joe<\/u>: I was looking over some of those trials we buried. Seroquel is kind of a lightweight in spite of all our hype, isn’t it?<\/em><\/font><\/sup><\/div>\n
Jim<\/u>: Yeah. I mean it’s well tolerated except for that pesky weight\/diabetes thing, and it seems to calm people down, puts them to sleep. But it’s a softy as antipsychotics go. It’s a shame. Getting it on the market was hard work and cost Zeneca a bundle.<\/em><\/font><\/sup><\/div>\n
Joe<\/u>: I’ve been wondering… What if, instead of seeing it as a wimpy<\/u> antipsychotic, we took advantage of that and called it a strong<\/u> anti-anxiety drug, or a novel<\/u> anti-depressant, or something like that? What’s going to fill the benzodiazepine niche anyway? <\/em><\/font><\/sup><\/div>\n
Jim<\/u>: <\/strong>You mean make a silk purse out of this sow’s ear? You’re a real dreamer, Joe! <\/em><\/font><\/sup><\/div>\n
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While I have no evidence that such a conversation ever took place in reality, it might as well have, because that’s what seems to have happened [even though Seroquel stayed in the battle of the Atypical Antipsychotics in treating Schizophrenia]. Whatever the thoughts behind the curtain, the idea of indication creep<\/font><\/strong> was there from the outset [Jeffrey Goldstein, November 1997<\/strong><\/a>]:<\/div>\n
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Looking at all these clinical trials graphs, I got to wondering if one could graph indication creep<\/font><\/strong> [a case of graph envy?]. I don’t think it’ll get me an NIMH grant, but I just counted the articles in pubmed<\/font><\/strong><\/a> that contained "QUETIAPINE" and had various words in the [TITLE]. It’s displayed with the F.D.A. approval dates in the table. …something of a story:<\/div>\n
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Each of the approvals is supported by Clinical Trials submitted to the F.D.A., [connecting the actual trial with the approval is difficult as there is very little information on the F.D.A. site for supplemental approvals]. But most of the studies are published. I’ve picked one of the recent ones as an example  because there’s greater likelihood of full disclosure and it is available full text on the Internet. This one is Seroquel XR as the sole treatment in MDD [Seroquel was not<\/u> approved as monotherapy in MDD on the grounds that the side effects outweigh the gain]: <\/div>\n
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Extended Release Quetiapine Fumarate Monotherapy for Major Depressive Disorder:<\/font><\/strong><\/a><\/div>\n
Results of a Double-Blind, Randomized, Placebo-Controlled Study<\/font><\/strong><\/a>
by Richard Weisler, J. Mark Joyce<\/font><\/strong>, Lora McGill<\/font><\/strong>, Arthur Lazarus<\/font><\/strong>, Johan Szamosi<\/font><\/strong>, and Hans Eriksson<\/font><\/strong>
CNS Spectrums<\/font><\/strong> 2009;14(6):299-313<\/div>\n

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Introduction<\/font><\/u><\/strong>: Once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy was evaluated in major depressive disorder (MDD).<\/sup><\/div>\n
Method<\/font><\/u><\/strong>: This was an 8-week (6-week randomized-phase; 2-week drug-discontinuation\/tapering phase), double-blind, parallel-group, placebo-controlled study. The primary outcome measure was Montgomery-Åsberg Depression Rating Scale (MADRS) total score randomization-to-Week 6 change. Other assessments included the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and adverse events (AEs).<\/sup><\/div>\n
Results<\/font><\/u><\/strong>: 723 patients were randomized: 182, 178, 179, and 184 to quetiapine XR 50, 150, 300 mg\/day, and placebo, respectively. At Week 6, significant reductions occurred in MADRS score with quetiapine XR 50 mg\/day (–13.56; P<.05), 150 mg\/day (–14.50; P<.01) and 300 mg\/day (–14.18; P<.01) versus placebo (–11.07); at Day 4, reductions for quetiapine XR (titrated to 50 or 150 mg\/day according to dose group) versus placebo (–2.9) were: –4.7 (P<.01), –5.2 (P<.001), and –5.1 (P<.001), respectively. At endpoint, MADRS response (≥50% reduction in score) was 42.7% (P<.01), 51.2% (P<.001), and 44.9% (P≤.001) for quetiapine XR 50, 150, and 300 mg\/day, respectively; 30.3% for placebo. Overall, quetiapine XR 150 mg\/day provided consistently more positive secondary efficacy results than 50 mg\/day and 300 mg\/day versus placebo. The most common AEs in quetiapine XR-treated patients were dry mouth, sedation, somnolence, headache, and dizziness.<\/sup><\/div>\n
Conclusion<\/font><\/u><\/strong>: In patients with MDD, quetiapine XR monotherapy (50\/150\/300 mg\/day) is effective in reducing depressive symptoms, with improvement from Day 4 onwards. Safety and tolerability were consistent with the known profile of quetiapine.<\/sup><\/div>\n
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Faculty Affiliations<\/u>: Dr. Weisler is Adjunct Professor of Psychiatry in the Department of Psychiatry at the University of North Carolina, Chapel Hill, and Adjunct Associate Professor of Psychiatry at Duke University, in Durham, North Carolina.<\/font><\/em><\/strong> Dr. Joyce is Principal Investigator at CNS Healthcare in Jacksonville, FL. and Dr. McGill is Lead Principal Investigator at CNS Healthcare in Memphis.<\/em><\/font><\/strong> Dr. Lazarus, Mr. Szamosi, and Dr. Eriksson are employees of AstraZeneca.<\/em><\/font><\/strong><\/sup><\/div>\n
Funding\/Support<\/u>: The study (Moonstone; D1448C00001) was funded by AstraZeneca. The study was registered at ClinicalTrials.gov (identifier number NCT00320268).<\/em><\/font><\/strong><\/sup><\/div>\n
Acknowledgments<\/u>: The authors would like to thank Jocelyn Woodcock, MPhil, from Complete Medical Communications, who provided medical writing support funded by AstraZeneca…<\/em><\/font><\/strong><\/sup><\/div>\n<\/blockquote>\n
They are fairly monotonous double-blind placebo-controlled 6 week trials using a variety of rating scales. The lead author is usually academically affiliated and a consultant of some sort for a number of Pharmaceutical Companies [20], on a number of speaker’s bureaus [21], and a recipient grants from Pharmaceutical Companies [43]. There may be authors from the Clinical Trials Industry [CNS Healthcare<\/font><\/strong><\/a><\/u>]. And there are always several authors from AstraZeneca<\/font><\/strong>. The studies are funded by AstraZeneca<\/font><\/strong>, as is the contract medical writer [Complete Medical Communications<\/font><\/strong><\/a><\/u>]. This formula appears to be the standard fare:<\/div>\n