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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n\u003Cp id=\u0022p-1\u0022\u003EOne significant issue facing patients currently on antidepressants is the loss of effect that may occur with chronic use of the drug, ie, the so called \u201cpoop-out\u201d effect. This article elaborates on this issue and discusses true drug responders versus placebo responders (those that have responded to the non-specific effects of treatment). Despite their response to treatment, there are no available clinical indicators to differentiate between these two types of responders.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPsychopharmacology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EOne significant issue facing patients currently on antidepressants is the loss of effect that may occur with chronic use of the drug, ie, the so called \u201cpoop-out\u201d effect. Elaborating on this issue, Mark Zimmerman, MD, Brown University School of Medicine, Providence, RI, states, \u201cWhen you see someone in your practice, and you put them on medication, and they respond, you are essentially seeing two types of individuals. Some are true drug responders. Some have responded to the non-specific effects of treatment. They are placebo responders.\u201d Despite their response to treatment, there are no available clinical indicators to differentiate between these two types of responders.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe fact that some individuals are placebo responders, may account for the majority of cases of relapse reported in medication continuation studies (Zimmerman M, Posternak MA, Ruggero CJ. \u003Cem\u003EJ Clin Psychopharmacology\u003C\/em\u003E 2007;27:177\u201381). One experimental design that is useful in parceling out the rate of relapse attributable to placebo responding is the \u201cExtension Design\u201d. In this paradigm, active medication or placebo is initially assigned in a double-blind fashion. Responders to active medication or placebo then go on to the continuation phase of the study with no change in their treatment. That is, individuals assigned to the medication group remain on medication, while those given placebo continue to receive placebo. This design allows for the question, what percentage of relapse in patients on active medication can be attributable to an initial placebo response?\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn order to calculate the percentage of relapse accounted for by placebo responding, four pieces of data are needed. In the acute phase of the experiment, the Response Rate to Medicine (RRM) and the Response Rate to Placebo (RRP) are needed to complete this calculation. In addition, the relapse rate in people who responded to medication (RLM) and the relapse rate in people who responded to placebo (RLP) must be obtained from the continuation phase of the study. Once this data is collected, the rate of relapse that may be attributable to initial placebo responding can be estimated.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn a hypothetical study, 150 patients received medication, and 100 of them responded, (RRM=66%). These 100 medication responders were continued on medication in the continuation phase where 30 patients relapsed (RLM=30%). 150 patients received placebo and 50 of them responded. (RRP=33%) These 50 were continued on placebo in the continuation phase where 25 of them relapsed (RLP=50%)\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EFirst, an estimate of the rate at which patients displayed a placebo response despite receiving active medication (ePR) is calculated by dividing the RRP by the RRM.\u003C\/p\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-1\u0022\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/highwire\/spmdc\/7\/2\/31\/embed\/graphic-1.gif\u0022\/\u003E\n\n\n\u003C\/span\u003E\u003Cp id=\u0022p-7\u0022\u003ESecond, how many patients treated with active drug in the continuation phase, who were responders in the acute phase, are presumptive placebo responders (PPR)? To get this figure, the number of patients receiving active medication in the continuation phase is multiplied by the placebo response rate calculated in the first step.\u003C\/p\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-2\u0022\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/highwire\/spmdc\/7\/2\/31\/embed\/graphic-2.gif\u0022\/\u003E\n\n\n\u003C\/span\u003E\u003Cp id=\u0022p-8\u0022\u003EThe number of patients treated with active medication in the continuation phase who have responded, but are expected to relapse because they are presumptive placebo responders (eRLP) can then be calculated by multiplying the PPR by the RLP.\u003C\/p\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-3\u0022\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/highwire\/spmdc\/7\/2\/31\/embed\/graphic-3.gif\u0022\/\u003E\n\n\n\u003C\/span\u003E\u003Cp id=\u0022p-9\u0022\u003EFinally, what percentage of relapse can be attributable to initial placebo responding? This final calculation is obtained by taking the number of presumptive placebo responders on active medication that have relapsed (ie, eRLP) and dividing by the total number of patients who relapsed on medication in the continuation phase.\u003C\/p\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-4\u0022\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/highwire\/spmdc\/7\/2\/31\/embed\/graphic-4.gif\u0022\/\u003E\n\n\n\u003C\/span\u003E\u003Cp id=\u0022p-10\u0022\u003EThus the in this study, presumably 83% of the patients who relapsed after responding to medication and continuing on medication in the continuation phase actually relapsed because they were placebo responders.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EUsing this method, researchers and clinicians may more accurately determine who is truly responding to their choice of medication versus those who may merely be placebo responders and, thus, more likely to \u201cpoop-out\u201d during the latter portion of their treatment.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/7\/2\/31.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlyw3\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}