Skip to main content

Expectations May Shape SSRI Effectiveness in Social Anxiety

October 20, 2017

Patients with social anxiety disorder who were led to believe their selective serotonin reuptake inhibitor (SSRI) was merely an active placebo were less likely to respond to the medication than patients who knew they were receiving an SSRI, according to a study published online in EBioMedicine.

The results, researchers said, suggest a marked placebo component related to expectancy in SSRI treatment.  

“We don’t think SSRIs are ineffective or lack therapeutic properties for anxiety,” said study leader Tomas Furmark, PhD, a professor at Uppsala University in Sweden, “but our results suggest that the presentation of the treatment may be as important as the treatment itself.”

SSRIs Linked With Elevated Risk of Birth Defects, Stillbirths

In the study, 46 patients with social anxiety disorder were treated with 20 mg of escitalopram daily over 9 weeks. At the study’s start, participants were randomized to 1 of 2 groups: an “overt treatment” group that received accurate treatment information or a “covert treatment” group told the drug was an active placebo that yielded similar side effects as an SSRI but without an expected clinical impact.

“Our results show that the number of responders was 3 times higher when correct information was given than when patients thought they were treated with an ineffective active placebo, even though the pharmacological treatment was identical,” said study author Vanda Faria, PhD.

New Study Supports SSRI Monotherapy in Bipolar II Disorder

What’s more, functional magnetic resonance imaging (fMRI) showed different effects on brain activity between the groups. Activations of the posterior cingulate cortex and the relationship between it and the amygdala, which is central in fear and anxiety, differed with patients’ expectations.

“This may reflect,” said coauthor Malin Gingnell, MD, PhD, “an interaction between cognition and emotion as the brain changes differently with medication depending on the patient’s expectancies.”

—Jolynn Tumolo


Faria V, Gingnell M, Motilla Hoppe J, et al. Do you believe it? Verbal suggestions influence the clinical and neural effects of escitalopram in social anxiety disorder: a randomized trial. EBioMedicine. 2017 September 26.

Patients’ expectations influence effectiveness of SSRI antidepressants [press release]. Uppsala, Sweden: Uppsala University; October 4, 2017.

Back to Top