One of the major challenges involved in clinical trials for major depressive disorder (MDD) is that of placebo response. The placebo response rate has been estimated at 20 - 50% of those subjects who enter a standard clinical trial for MDD. This high rate of response to placebo, which may not differ substantially from the response rate to medication, can make it difficult to demonstrate the efficacy of new antidepressant compounds. Identification of MDD subjects with a placebo responder (PR) phenotype, either at the beginning or end of a clinical trial, could have two major potential benefits. First, identification of placebo responders prior to enrollment in a clinical trial might make it possible to have restrictive entry criteria, excluding such subjects from the trial. Segregation of PR phenotype subjects a priori could reduce variance in the outcome data and increase the drug-placebo difference. This exclusion could reduce the number of subjects required for clinical trials and render the trials more efficient. Second, identification of a PR phenotype during a clinical trial could make it possible to distinguish "true medication" from placebo response. This distinction could make it possible to identify subgroups in the trial, enhancing precision in the study of medication effects.