{"id":66861,"date":"2016-07-14T06:00:06","date_gmt":"2016-07-14T10:00:06","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=66861"},"modified":"2016-07-14T19:56:36","modified_gmt":"2016-07-14T23:56:36","slug":"listening-to-placebo-i","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/07\/14\/listening-to-placebo-i\/","title":{"rendered":"listening to placebo…"},"content":{"rendered":"
"Another issue with pediatric clinical trials is that 61 percent of youth respond to the drugs, but 50 percent respond to placebo, compared with 30 percent among adults, making it hard to separate effects."<\/font><\/em><\/sup><\/div>\n
                Karen Dineen Wagner<\/font><\/sup><\/div>\n
                in<\/font><\/em> Child Psychiatrists Look at Specialty From Both Macro, Micro Perspectives<\/a><\/sup><\/div>\n

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\"PaxilThe Placebo Effect<\/a> in Clinical Trials is more than a philosophical matter. It’s a practical consideration, something that is regularly subtracted from the overall effect in presenting the results, yet it’s poorly understood itself. For some, it’s seen as the sampling phenomenon referred to as the regression to the mean<\/font><\/em> [see in the land of sometimes[4]…<\/a>]; for others, it’s suggestability and expectation; and there’s also a literature exploring a genetic\/neurobiological component. But just looking at the graphs, one might well conclude that simply being in as trial is itself a therapy.<\/font><\/em> The placebo effect is certainly a prominent effect in the adolescent antidepressant trials that have frequently graced these pages. Here’s an interesting deconstruction specifically attempting to parse out the role of expectation of benefit<\/font><\/em> in these trials:<\/div>\n
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Deconstructing Pediatric Depression Trials: An Analysis of the Effects of Expectancy and Therapeutic Contact<\/a><\/div>\n
by Bret R. Rutherford M.D., Joel R. Sneed Ph.D., Jane M. Tandler H.S., David Rindskopf Ph.D., Bradley S. Peterson M.D. and Steven P. Roose M.D.<\/div>\n
Journal of the American Academy of Child & Adolescent Psychiatry.<\/font><\/strong> 2011 50[8]:782-95.<\/div>\n
[full text on-line<\/a>]<\/div>\n

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Objective<\/u>:<\/font><\/strong><\/em> This study investigated how study type, mean patient age, and amount of contact with research staff affected response rates to medication and placebo in acute antidepressant trials for pediatric depression.<\/div>\n
Method<\/u>:<\/font><\/strong><\/em> Data were extracted from nine open, four active comparator, and 18 placebo-controlled studies of antidepressants for children and adolescents with depressive disorders. A multilevel meta-analysis examined how study characteristics affected response rates to antidepressants and placebo.<\/div>\n
Results<\/u>:<\/font><\/strong><\/em> The primary finding was a main effect of study type across patient age and contact amount, such that the odds of medication response were greater in open versus placebo-controlled studies [odds ratio 1.87, 95% confidence interval 1.17–2.99, p = .012] and comparator studies [odds ratio 2.01, 95% confidence interval 1.16–3.48, p = .015] but were not significantly different between comparator and placebo-controlled studies. No significant main effects of patient age or amount of contact with research staff were found for analyses of response rates to medication and placebo. Response to placebo in placebo-controlled trials did significantly increase with the amount of therapeutic contact in older patients [age by contact; odds ratio 1.08, 95% confidence interval 1.01–1.15, p = .038].<\/div>\n
Conclusions<\/u>:<\/font><\/strong><\/em> Although patient expectancy strongly influences response rates to medication and placebo in depressed adults, it appears to be less important in the treatment of children and adolescents with depression.<\/font><\/strong><\/em> Attempts to limit placebo response and improve the efficiency of antidepressant trials for pediatric depression should focus on other causes of placebo response apart from expectancy.<\/div>\n<\/blockquote>\n
This topic has been in my mind since our RIAT Project on Paxil Study 329<\/a>. I had three versions of the Protocol. The 1993 and 1996 a priori versions said:<\/div>\n
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"Medical Management<\/font><\/strong><\/em><\/div>\n

Psychotherapy Experience in protocols in depressed adolescents suggest that patients and families expect psychotherapy and are reluctant to consider a course of medication treatment alone, especially where the medication may be solely placebo. On the other hand, a provision of treatment with a psychotherapy which, in retrospect, turned out to be extraordinarily efficacious might well preclude the demonstration of a real, significant, and clinically meaningful medication effect. There are currently several research groups beginning the process of examining different specific psychotherapies [e.g. cognitive behavioral and interpersonal] for adolescent depression. As of yet, however, there are no completed controlled studies which would suggest a "reference" psychotherapy treatment. The present study will include supportive psychotherapy, similar to the management as described by Fawcett in Appendix G.<\/font><\/strong><\/em><\/p>\n

Weekly visits will consist of a 45 minute visit with the therapist. In unusual circumstances, emergency contact of greater duration is permitted. Duration of all contact including phone calls will be systematically documented.<\/font><\/strong><\/em>"<\/div>\n<\/blockquote>\n
And the version in the Full Acute Study Report<\/font><\/a> [page 35] for that study said:<\/div>\n
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"3.5.4 Other Protocol-specified Therapy<\/font><\/strong><\/em><\/div>\n


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Supportive psychotherapy for the depressive episode was provided in a manner similar to that described by Fawcett and coworkers in the Adolescent Depression Collaborative Research Group.<\/font><\/strong>[10] Psychotherapy was intended to provide the psychosocial interaction between the patient and the therapist that would permit observation of any pharmacotherapeutic effect of the study medication. Therefore, the sessions were to focus on providing supportive therapy rather than implementing interpersonal or cognitive\/behavioral strategies. At each weekly visit, the patient had a 45-minute visit with the therapist.<\/font><\/strong> However, emergency contact of greater duration was permitted under unusual circumstances.<\/em>"<\/div>\n<\/blockquote>\n
As for the Fawcett document explicitly spelling out the supportive psychotherapy mentioned, it’s in Appendix A of the 329 Study Report, freely available online here<\/a> [Note: see below<\/font><\/strong>]. It goes on for 20 plus pages, ending with a list of DOs and DONTs<\/a> that captures the essence of the recommendations:<\/div>\n
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DO’S:<\/div>\n