Placebo effect in the treatment with antidepressants : Implications for the scientific evaluation and clinical use of pharmaceutical treatments of depression

Abstract

Blinded placebo treatment arms in clinical trials often achieve up to 80% of the clinical improvements of the verum groups. Apparently, the majority of the effects found in the antidepressant groups in clinical trials are due to factors that are not specific to antidepressant treatment. This article reviews the factors that contribute to the high effectiveness of placebo interventions for antidepressants. Anarrative literature review is presented with particular emphasis on placebo effects in antidepressant clinical trials. There is aparticularly strong placebo effect in depression compared to other mental disorders. The magnitude of this effect can be modulated by helpful versus nonhelpful instructions, by patient participation in the decision-making process but also by personal attention, especially if the clinician is perceived as competent and warmhearted. The occurrence of subtle side effects can also reinforce placebo effects. Placebo effects are not only reflected in subjective patient-reported outcome variables but are also evident in neurochemical changes in the body. Clinicians essentially contribute to the effectiveness of antidepressant treatment through their own behavior. At the same time, the relatively small overall difference between verum and placebo treatments for depression leads to the necessity of acritical evaluation of the cost-benefit ratio, adapted to the individual case. Study designs for the evaluation of antidepressants are required that better reflect the complex interactions between the genuine drug effects and placebo effects.