SSRI Antidepressant Effectiveness Influenced By Expectations

The way in which depression treatment with selective serotonin reuptake inhibitors is described to the patient can be as important as the treatment itself, a new study suggests.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and anxiety but their superiority over placebo has been questioned, provoking debate among researchers and clinicians.

It has been argued that SSRIs may lack specific therapeutic properties and that their beneficial effects observed in clinical trials, could be explained by different expectancies in the drug and placebo groups.

In a double-blind study, the participant may come to realize that he or she has been given the drug instead of placebo because of the experienced side effects, and this may in turn result in increased expectations of improvement and a better effect is reported. However, as of yet, it has not been tested experimentally to what extent the clinical effect of SSRIs can be influenced by the patient’s expectancies induced by the information patients are given at prescription.

Escitalopram Treamtment

A group of researchers at Uppsala University’s Department of Psychology has now demonstrated considerably better effects of the SSRI escitalopram when given with correct as compared to incorrect verbal information.

In the randomized study, all patients with social anxiety disorder were treated with the same dosage of escitalopram for nine weeks, but only one group was correctly informed about the drug and its effectiveness.

By use of a cover story the other group was led to believe they were treated with a so called ‘active placebo’, yielding similar side effects as the SSRI but out of which no clinical improvement could be expected.

“Our results show that the number of responders was three 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,”

says author Vanda Faria.

Cognition And Emotion

Futhermore, assessments with MR neuroimaging showed that the SSRI had different effects on brain activity when associated with expectations of improvement or not. There were differences between the two groups in activations of the posterior cingulate cortex and the coupling between this region and the amygdala which is central to fear and anxiety.

“This may reflect an interaction between cognition and emotion as the brain changes differently with medication pending on the patient’s expectancies,”

says co-author Malin Gingnell.

The results imply a marked placebo component, related to expectancies, in SSRI treatment, underscoring the importance of the communication between prescriber and patient.

“We don’t think SSRIs are ineffective or lack therapeutic properties for anxiety but our results suggest that the presentation of the treatment may be as important as the treatment itself,”

says Professor Tomas Furmark, who led the study.

Financial support was provided by the Swedish Research Council for Working Life and Social Research, the Swedish Research Council, and Riksbankens Jubileumsfond – the Swedish Foundation for Humanities and Social Sciences.

Faria, Vanda et al.
Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial
EBioMedicine DOI: http://dx.doi.org/10.1016/j.ebiom.2017.09.031

Image: Mirjana Veljovic/Flickr