An active placebo is a substance that produces side effects similar to an active ingredient while not producing the same intended therapeutic effect. The aim of this study is to review the literature on the hypothesis of the active placebo response as a mechanism of action of antidepressants. It was found that persons who expect the occurrence of side effects of a pure placebo taken under the guise of an antidepressant present a higher degree of depressive symptoms than persons who do not expect the occurrence of side effects. There are reasons to believe that the entirety or part of the difference in the effectiveness of antidepressants and placebo is due to the fact that participants of the clinical trials correctly guess which study group they have been assigned to.