Placebo mechanisms in depression: An experimental investigation of the impact of expectations on sadness in female participants

J Affect Disord. 2019 Sep 1;256:658-667. doi: 10.1016/j.jad.2019.06.070. Epub 2019 Jul 2.


Introduction: We aimed to examine whether drug-associated expectations have an impact on the experience of sadness. We hypothesized that participants who received an active placebo nasal spray (but were told that it was an antidepressant that would protect them from experiencing negative emotions) would become less sad than the control groups.

Methods: 128 healthy female participants were randomly allocated to one of four groups: the experimental group, which received an active placebo and the expectancy-modifying instructions ("Protection: the spray protects from experiencing negative emotions", n = 32), or one of three different control groups ("Sensitization": the spray sensitizes to negative emotions", n = 31; "Placebo: the spray is a placebo", n = 32; and "Control: no nasal spray", n = 32) RESULTS: In line with our hypotheses, the experimental group experienced significantly less sadness after having watched a sadness provoking film sequence compared to the three control groups, with medium- to large effect sizes (Hedge´s gs 0.59-0.87).

Discussion: Our results suggest that sadness can be significantly influenced by placebos in the short-term. Our study further suggests that knowledge about the effect of placebos on depressive symptoms should be utilized in clinical practice. However, depression is a complex disorder and antidepressants address a wide range of symptoms associated with depression such as suicidal thoughts, disturbed sleep and loss of energy. Further research on the placebo effects associated with the antidepressant treatment is needed.

Limitations: concern generalizability to treatment because sadness is only one potential symptom of depression and antidepressants often also address other symptoms.

Keywords: Antidepressant trials; Expectations in depression; Mood induction; Placebo; Sadness.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Antidepressive Agents / administration & dosage*
  • Depression / drug therapy
  • Depression / psychology*
  • Female
  • Humans
  • Motivation*
  • Placebo Effect
  • Sadness / drug effects
  • Sadness / psychology*
  • Young Adult


  • Antidepressive Agents