\nStudy Finds Olanzapine-Fluoxetine Combo Superior to Placebo for Bipolar Disorder in Children<\/a><\/div>\nPSYCHIATRIC<\/font>NEWS<\/font> <\/strong>alert<\/strong> <\/font><\/div>\n[The Voice of the<\/font><\/strong> American Psychiatric Association<\/a> and the Psychiatric Community]<\/font><\/strong> <\/div>\nDecember 30, 2014<\/div>\nA combination of the antipsychotic olanzapine and the antidepressant fluoxetine proved superior to placebo for acute treatment of bipolar I depression in patients aged 10-17 in a randomized control trial published online<\/a> in the Journal of the American Academy of Child and Adolescent Psychiatry<\/em>.<\/p>\n
The double-blind study by researchers at Eli Lilly and Company randomized 170 young patients with bipolar I disorder experiencing an acute depressed episode to the olanzapine\/fluoxetine combination [OFC] and 85 to placebo for up to eight weeks of treatment. The primary efficacy measure was mean change in the Children’s Depression Rating Scale-Revised [CDRS-R]…<\/div>\n<\/blockquote>\nThe issue of the hour is DATA TRANSPARENCY<\/font> in Randomized Clinical Trials [RTCs], mainly industry funded RTCs of medications, particularly those submitted for FDA Approval. This announcement in the PSYCHIATRIC<\/font>NEWS<\/font> <\/strong> came out the same day the study was published [on-line] in the JAACAP. There are several reasons one might want to look into this announcement. First, the Pediatric Bipolar I diagnosis is controversial, to say the least. It was quite the rage for a time after being introduced by Dr. Joseph Biederman and colleagues at Harvard and swept through the Child Psychiatry world. In 2008, Dr. Biederman was on Senator Grassley’s list for undisclosed pharmaceutical income and later censured by Harvard, the fad began to pass. Many doubt that Bipolar Disorder in the pediatric age group even exists, or at least exists in any sizable number. Second, these are old drugs – Prozac®<\/font> and Zyprexa®<\/font>. Why is Lily promoting its combo version [Symbiax®<\/font>] at this late date? Why are they publishing a trial in kids now when both Prozac®<\/font> and Zyprexa®<\/font> are off-patent? But the thing that struck me about this announcement is what it doesn’t say. It doesn’t say:<\/div>\n\n
The double-blind study by <\/font>Dr Melissa DelBello with the Division of Bipolar Disorders Research, University of Cincinnati College of Medicine,<\/font><\/strong> randomized 170 young patients with Bipolar I disorder experiencing an acute depressed episode to the olanzapine\/fluoxetine combination [OFC] and …<\/font><\/em><\/div>\n<\/ul>\n… even though she’s the only psychiatrist [and<\/u> the only non-Lily employee] on the author byline. And, by the way, she was on Senator Grassley’s list too as an academic with undisclosed PHARMA income:<\/div>\n\nOlanzapine\/Fluoxetine Combination in Children and Adolescents With Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Trial<\/font><\/strong><\/div>\nby Holland C. Detke, Ph.D., Melissa P. DelBello, M.D.<\/font><\/strong>, John Landry, M.Math, and Roland W. Usher, M.S.<\/div>\nJournal of the American Academy of Child and Adolescent Psychiatry<\/font><\/strong>. published online 12\/24\/2014<\/div>\n<\/p>\n
Objective<\/font><\/strong>: To assess the efficacy and safety of olanzapine\/fluoxetine combination [OFC] for the acute treatment of bipolar depression in children and adolescents. <\/div>\nMethod<\/font><\/strong>: Patients 10-17 years of age with bipolar I disorder [BP-I], depressed episode, baseline Children’s Depression Rating Scale-Revised [CDRS-R] total score ≥40, Young Mania Rating Scale [YMRS] total score ≤15, and YMRS-item 1 ≤2 were randomized to OFC [6\/25-12\/50 mg\/day olanzapine\/fluoxetine; n=170] or placebo [n=85] for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated measures methodology. <\/div>\nResults<\/font><\/strong>: Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients [-28.4 vs. -23.4, p=.003; effect size=.46], with between-group differences statistically significant at week 1 [p=.02] and all subsequent visits [all p<.01]. Rates of and times to response and remission were statistically significantly greater for OFC- than placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient’s endpoint was significantly greater for OFC- than placebo-treated patients [4.4 kg vs. 0.5 kg, p<.001]. Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval [QTc] were also common or very common but generally not clinically significant. <\/div>\nConclusion<\/font><\/strong>: OFC was superior to placebo and approved by the US Food and Drug Administration [FDA] for the acute treatment of bipolar I depression in patients 10-17 years of age. Benefits should be weighed versus the risk of adverse events, particularly weight gain and hyperlipidemia.<\/div>\n<\/blockquote>\nUnlike the industry RCTs in the past where the academic authors are mentioned up front, the announcement says "The double-blind study by researchers at Eli Lilly and Company randomized.<\/em>.." [at least they’re honest]. So this is an industry study inserted directly into the academic, peer reviewed literature. And who did the study? who wrote it? There’s probably an answer to that question in the acknowledgements in the paper:<\/div>\n\n
"The authors also thank Shannon Gardell, PhD, and Rodney Moore, PhD, of inVentiv Health Clinical<\/a> [funded by Eli Lilly and Co.] for assistance in drafting\/editing the manuscript.<\/font><\/em>"<\/div>\n<\/ul>\ninVentiv Health Clinical<\/a> is a full service Clinical Research Organization [CRO] that likely both managed the study for Lily and wrote [ghost wrote<\/em>] the paper. A glance at Dr. DeBello’s COI declaration tells us that she’s certainly still in the pharmaceutical orbit:<\/div>\n\n
Dr. DelBello has received grant or research support from … Amylin Pharmaceuticals, Eli Lilly and Co.<\/font><\/strong>, Pfizer, Otsuka, Merck, Martek, Novartis, Lundbeck, Purdue, Sunovion, and Shire. She has served as a consultant to Bracket, Guilford, Pfizer, Dey Pharma, Lundbeck, Springer, Sunovion, and Supernus…<\/font><\/em><\/div>\n<\/ul>\nFrom its approval in 2003 to 07\/26\/2013, Symbiax® was not approved for Pediatric Use. At that time, the label was changed<\/a> [Drugs@FDA<\/font><\/strong>] and the patent was extended [Pediatric Extension?<\/font><\/strong> – FDA Orange Book<\/a>]:
<\/font><\/div>\n\n\n
Children and Adolescents<\/u> — The efficacy of SYMBYAX for the acute treatment of depressive episodes associated with Bipolar I Disorder was established in a single 8-week, randomized, double-blind, placebo -controlled study of patients, 10 to 17 years of age [N=255], who met Diagnostic and Statistical Manual 4th edition-Text Revision (DSM-IV-TR) criteria for Bipolar I Disorder, Depressed.<\/font><\/em><\/div>\n<\/ul><\/div>\nThe FDA Approval in adolescents was apparently based on this study. <\/div>\nIt’s not my intention to specifically challenge these results. But since the DSM-III, there has been a steady creep in diagnosing Bipolar Disorder from the classic Manic-Depressive Illness of Kraepelin’s days. And I see a remarkable number of people who announce that they’ve been "told they are Bipolar<\/em>" and they simply don’t fit. Also, in reviewing the more papers on Pediatric Bipolar Disorder, my skepticism level hovers around DEFCON 1. Likewise, I see no reason for a COMBO medication. Taking two pills a day if they’re needed is no great burden. So my suspicions that the goals here are commercial rather than medical. But I don’t doubt that depressed adolescents feel better taking Zyprexa® or Symbiax®. I question whether it’s a good idea to prescribe it, particularly in the fixed dose COMBO pills. But the fact that it is a likely ghost-written, industry produced, COI-laden, commercially-driven RCT is not all that bothers me about this study.<\/p>\n
Stay tuned…<\/div>\n","protected":false},"excerpt":{"rendered":"Study Finds Olanzapine-Fluoxetine Combo Superior to Placebo for Bipolar Disorder in Children PSYCHIATRICNEWS alert [The Voice of the American Psychiatric Association and the Psychiatric Community] December 30, 2014 A combination of the antipsychotic olanzapine and the antidepressant fluoxetine proved superior to placebo for acute treatment of bipolar I depression in patients aged 10-17 in a […]<\/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":[5],"tags":[],"class_list":["post-52718","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/52718","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=52718"}],"version-history":[{"count":17,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/52718\/revisions"}],"predecessor-version":[{"id":52735,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/52718\/revisions\/52735"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=52718"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=52718"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=52718"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}