Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety but their superiority over placebo has been questioned, generating considerable debate among researchers and clinicians. In a new study, Uppsala University researchers show that the way in which the treatment is described to the patient can be as important as the treatment itself.

In the debate among clinics and researchers on SSRIs, 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 realise 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.

In a study published in the journal EBioMedicine, a group of researchers at Uppsala University’s Department of Psychology, Sweden, now demonstrate considerably better effects of the SSRI escitalopram when given with correct as compared to incorrect verbal information.

In the randomised 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,” said author Vanda Faria.

Moreover, 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,” said 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,” said Professor Tomas Furmark, who led the study.