During the last decade, there has been an increasing use of a placebo run-in period prior to randomization to active treatments, or placebo in randomized controlled trials aimed at establishing acute phase antidepressant drug efficacy in patients with major depression. This procedure is thought to reduce response rates to placebo treatment after randomization, thereby increasing the drug-placebo difference. Metaanalyses of 101 studies reveal that a placebo run-in does not (1) lower the placebo response rate, (2) increase the drug-placebo difference, or (3) affect the drug response rate post-randomization in either inpatients or outpatients for any antidepressant drug group. If there is a post-randomization placebo treatment cell, drug response rates are unchanged or are slightly lower than if there is no placebo treatment cell for outpatients. These results suggest that a pill placebo run-in provides no advantage in acute phase efficacy trials.