Does elimination of placebo responders in double-blind placebo-controlled randomized clinical trials of SSRI antidepressants in depression influence the size of the treatment effect?, a meta-analytic evaluation

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Lee, Sandra
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Randomized clinical trials are accepted as the ost effective method to assess the safety and effectiveness of a new drug or clinical intervention. Often, the results of a randomized clinical trial will allow a new drug to be introduced into current clinical practice. Clinical investigators and the pharmaceutical industry naturally want to optimize treatment effect. Thus, many randomized clinical trials, especially those involving psychotropic drugs, are preceded by a "placebo run-in phase", in which all subjects are given the placebo and any subject who responds to the placebo are withdrawn from the study prior to randomization. The objective of this research is to compare the effect size of randomized controlled placebo clinical trials (in the treatment of depression) that include a placebo run-in phase with those that do not include a placebo run-in phase, using a meta-analytic approach. It is hypothesized that the size of the treatment effect will be larger in studies that eliminate placebo responders from the study after a placebo run-in phase. A literature search was carried out to find all available published randomized clinical trials involving the use of a selective serotonin reuptake inhibitor antidepressant and placebo. Data were extracted from the trials and statistical analysis was completed using the international Cochrane Collaboration Review Manager software. The results indicate that there is no statistically significant difference in effect size between the clinical trials that have a placebo run-in phase followed by withdrawal of placebo responders and those trials that do not have such a phase. Recommendations for future research are discussed.