{"id":37579,"date":"2013-06-18T00:01:55","date_gmt":"2013-06-18T04:01:55","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=37579"},"modified":"2015-01-09T22:33:25","modified_gmt":"2015-01-10T03:33:25","slug":"has-to-stop","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/06\/18\/has-to-stop\/","title":{"rendered":"has to stop…"},"content":{"rendered":"\n

Dr. Charlie Nemeroff gave his lecture yesterday at the Institute of Psychiatry<\/font> [IoP], Kings College<\/font>, London<\/font> at the inauguration of their new Affective Disorders Centre amid protests from both sides of the Atlantic [including mine coffee-house<\/em> science…<\/a>, two footnotes…<\/a>, mystified in america…<\/a>, still mystified in america…<\/a>, character is pervasive…<\/a>]. His topic was The Neurobiology of Childhood Abuse: Treatment Implications<\/font><\/strong><\/em>.<\/p>\n

Dr. Bernard Carroll had weighed in with a comment<\/a> at Pharmalot<\/font><\/strong>, but today he has a blog post of his own at Healthcare Renewal<\/font><\/strong> about the IoP lecture [PROFESSOR NEMEROFF GOES TO LONDON: THREE STRIKES AND …<\/a>]. After summarizing Dr. Nemeroff’s well known history of ethical misadventures, he added a story about Dr. Nemeroff’s presentations on this particular topic that was news to me, and I thought it was worth running down. From Healthcare Renewal<\/font><\/strong>:<\/div>\n
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Professor Nemeroff’s sole publication of original data in this area appeared in 2003. It was a secondary analysis of a large clinical trial, first reported in 2000, that originally did not consider child abuse as a moderating variable in the response of chronically depressed patients to an antidepressant [nefazodone] or to cognitive behavior therapy [CBASP]. The 2003 report claimed that, in patients with a history of childhood trauma, response to CBASP was superior to response to nefazodone. At the same time there was no significant difference in response rates to drug or to CBASP between patients with or without childhood trauma histories. A portion of this report was later retracted because the data concerning reduction of Hamilton depression scores had been misrepresented.<\/font><\/strong><\/sup><\/div>\n<\/blockquote>\n
Here’s the abstract from PubMed that mentions an Erratum: <\/div>\n
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Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma<\/a>.
by Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT, McCullough JP Jr, Weiss PM, Dunner DL, Rothbaum BO, Kornstein S, Keitner G, Keller MB.<\/strong><\/sup>
Proceedings of the National Academy of Science<\/font><\/strong>. 2003 100[24]:14293-14296.
[full text on-line<\/a>]
Erratum [see below]<\/strong><\/sup><\/div>\n

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Major depressive disorder is associated with considerable morbidity, disability, and risk for suicide. Treatments for depression most commonly include antidepressants, psychotherapy, or the combination. Little is known about predictors of treatment response for depression. In this study, 681 patients with chronic forms of major depression were treated with an antidepressant [nefazodone], Cognitive Behavioral Analysis System of Psychotherapy [CBASP], or the combination. Overall, the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment. Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), psychotherapy alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the childhood abuse cohort. Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma.<\/strong><\/sup><\/div>\n<\/blockquote>\n
  Here’s the text of the 2005 Erratum in PNAS describing the error:<\/div>\n
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Erratum in Proceedings of the National Academy of Science<\/font><\/strong>. 2005 102[45):16530.
[full text on-line<\/a>]<\/strong><\/sup><\/div>\n

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MEDICAL SCIENCES<\/font><\/u>. For the article "Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma," which appeared in the Proc. Natl. Acad. Sci. in November 13, 2003, the authors note the following. "Results of the analyses of variance comparing change in Hamilton Rating Scale for Depression scores as a function of treatment type and early life trauma histories as well as Fig. 1A reflect change relative to the first week of treatment instead of baseline<\/font>. When change scores relative to baseline are used, the interaction effects between treatment type and childhood trauma histories are not statistically significant. This discrepancy is due to marked changes in depression scores during the first week of treatment. Note that all analyses comparing the more conservative outcome measure of remission as a function of treatment type and childhood trauma as well as Fig. 1B are correct. Thus, consideration of treatment response relative to baseline does not detect the effect of childhood trauma on final remission<\/font>, whereas consideration of final response relative to first response does detect the effect."<\/strong><\/sup><\/div>\n<\/blockquote>\n
This is reported as if it’s simply an error, but to my reading, it’s a fatal error<\/font><\/strong><\/em>. The whole point of the article is that in this depressed cohort, those with child abuse histories responded to Cognitive Psychotherapy but not to Antidepressants. That’s the title of the article! And it wasn’t significant after all! They had done their statistics using the week 1 data rather than the baseline!<\/font><\/strong><\/em> This error invalidates the whole study. I can find no evidence that the now invalidated article was retracted, just that the error was reported. Last week [character is pervasive…<\/a>], I had said, "…having heard and read Dr. Nemeroff’s body of work for over twenty years, it has always felt like teflon science.<\/em>" This is the kind of thing I was talking about – slippery, always slippery. So I thought I’d follow the thread of this article backwards to its source. And that’s when I fell into the deepest of holes, and down I tumbled. I’ll spare you all the sites I saw along the way, and get straight to what was at the bottom of the hole – this article in the New England Journal of Medicine:<\/div>\n
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A Comparison of Nefazodone, the Cognitive Behavioral-Analysis System of Psychotherapy, and Their Combination for the Treatment of Chronic Depression<\/a>
by Martin B. Keller, M.D.<\/font>, James P. McCullough, Ph.D., Daniel N. Klein, Ph.D., Bruce Arnow, Ph.D., David L. Dunner, M.D., Alan J. Gelenberg, M.D., John C. Markowitz, M.D., Charles B. Nemeroff, M.D.<\/font>, Ph.D., James M. Russell, M.D., Michael E. Thase, M.D.<\/font>, Madhukar H. Trivedi, M.D.<\/font>, Janice A. Blalock, Ph.D., Frances E. Borian, R.N., Darlene N. Jody, M.D., Charles DeBattista, D.M.H., M.D., Lorrin M. Koran, M.D., Alan F. Schatzberg, M.D.<\/font>, Jan Fawcett, M.D., Robert M.A. Hirschfeld, M.D., Gabor Keitner, M.D., Ivan Miller, Ph.D., James H. Kocsis, M.D., Susan G. Kornstein, M.D., Rachel Manber, Ph.D., Philip T. Ninan, M.D., Barbara Rothbaum, Ph.D., A. John Rush, M.D.<\/font>, Dina Vivian, Ph.D., and John Zajecka, M.D.<\/strong><\/sup>
New England Journal of Medicine<\/font><\/strong>. 2000 342[20]:1462-1470.
[full text on-line<\/a>]<\/strong><\/sup><\/div>\n

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Methods<\/font><\/u>: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone [maximal dose, 600 mg per day], the cognitive behavioral-analysis system of psychotherapy [16 to 20 sessions], or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression [indicating clinically significant depression]. Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients’ treatment assignments.<\/div>\n
Results<\/font><\/u>: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response [both remission and satisfactory response] was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group [P<0.001 for both comparisons]. Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group [P<0.001 for both comparisons]. The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug [e.g., headache, somnolence, dry mouth, nausea, and dizziness].<\/div>\n
Conclusions<\/font><\/u>: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.<\/div>\n

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[reformatted for clarity]<\/strong><\/sup><\/p>\n<\/blockquote>\n

So it started life in 2000 as a Bristol-Myers Squibb<\/font><\/strong> funded, non-placebo controlled trial comparing Nefazodone to CBT to both with 29 authors<\/font><\/strong>. Of interest, in the same issue<\/font><\/strong>, then NEJM Editor Marcia Angell<\/font><\/strong> wrote an editorial focused on this specific article<\/em>, the first of what would later become her book and campaign against conflicts of interest. It began:<\/div>\n
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Is Academic Medicine for Sale?<\/a>
by MARCIA ANGELL, MD<\/strong><\/sup>
New England Journal of Medicine<\/font><\/strong>. 342[20]:1516-1518.
[full text on-line<\/a>]<\/strong><\/sup><\/div>\n
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In 1984 the Journal became the first of the major medical journals to require authors of original research articles to disclose any financial ties with companies that make products discussed in papers submitted to us. We were aware that such ties were becoming fairly common, and we thought it reasonable to disclose them to readers. Although we came to this issue early, no one could have foreseen at the time just how ubiquitous and manifold such financial associations would become. The article by Keller et al. in this issue of the Journal provides a striking example. The authors’ ties with companies that make antidepressant drugs were so extensive that it would have used too much space to disclose them fully in the Journal. We decided merely to summarize them and to provide the details on our Web site.<\/font><\/p>\n

Finding an editorialist to write about the article presented another problem. Our conflict-of-interest policy for editorialists, established in 1990, is stricter than that for authors of original research papers. Since editorialists do not provide data, but instead selectively review the literature and offer their judgments, we require that they have no important financial ties to companies that make products related to the issues they discuss. We do not believe disclosure is enough to deal with the problem of possible bias. This policy is analogous to the requirement that judges recuse themselves from hearing cases if they have financial ties to a litigant. Just as a judge’s disclosure would not be sufficiently reassuring to the other side in a court case, so we believe that a policy of caveat emptor is not enough for readers who depend on the opinion of editorialists……<\/div>\n

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There are a number of things to say about this little trip down memory lane:<\/div>\n