Which factors predict placebo response in anxiety disorders and major depression? An analysis of placebo-controlled studies of escitalopram

J Clin Psychiatry. 2006 Nov;67(11):1741-6. doi: 10.4088/jcp.v67n1111.


Background: The placebo response rate has increased in several psychiatric disorders and is a major issue in the design and interpretation of clinical trials. The current investigation attempted to identify potential predictors of placebo response through examination of the placebo-controlled clinical trial database for escitalopram in 3 anxiety disorders and in major depressive disorder (MDD).

Method: Raw data from placebo-controlled studies (conducted from 2002 through the end of 2004) of escitalopram in patients meeting DSM-IV criteria for MDD and anxiety disorders (generalized anxiety disorder [GAD], social anxiety disorder [SAD], panic disorder) were used. Potential predictors examined were type of disorder, location of study, dosing regimen, number of treatment arms, gender of patients, and duration and severity of disorder.

Results: Placebo response (defined as the percent decrease from baseline in the reference scale) was higher in GAD and MDD studies conducted in Europe (p < .0001 and p = .0006, respectively) and was not associated with gender or duration of episode. In GAD, the placebo response rate was higher in a European fixed-dose study, which also had more treatment arms. In SAD and in U.S. specialist-treated MDD, a higher placebo response rate was predicted by decreased baseline disorder severity.

Conclusion: Additional work is needed before definitive recommendations can be made about whether standard exclusion criteria in clinical trials of antidepressants, such as mild severity of illness, maximize medication-to-placebo differences. This analysis in a range of anxiety disorders and MDD suggests that there may be instances in which the predictors of placebo response rate themselves vary across different conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage*
  • Anxiety Disorders / classification
  • Anxiety Disorders / drug therapy*
  • Citalopram / administration & dosage*
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Humans
  • Male
  • Placebo Effect
  • Treatment Outcome


  • Antidepressive Agents
  • Citalopram