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Expectations Influence Effectiveness of SSRIs

Summary: Study reveals people are three times more likely to report SSRIs are effective for their depression and anxiety when given the correct information about the medication.

Source: Uppsala University.

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 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,” says author Vanda Faria.

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Moreover, assessments with MR neuroimaging showed that the SSRI had different effects on brain activity when associated with expectations of improvement or not. NeuroscienceNews.com image is in the public domain.

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,” 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.

About this neuroscience research article

Funding: The Swedish Research Council for Working Life and Social Research, the Swedish Research Council, Riksbankens Jubileumsfond – the Swedish Foundation for Humanities and Social Sciences.

Source: Tomas Furmark – Uppsala University
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial” by Vanda Faria, Malin Gingnell1, Johanna Motilla Hoppe, Olof Hjorth, Iman Alaie, Andreas Frick, Sara Hultberg, Kurt Wahlstedt, Jonas Engman, Kristoffer N.T. Månsson, Per Carlbring, Gerhard Andersson, Margareta Reis, Elna-Marie Larsson, Mats Fredrikson, and Tomas Furmark in EBioMedicine. Published online September 26 2017 doi:10.1016/j.ebiom.2017.09.031

Cite This NeuroscienceNews.com Article
Uppsala University “Expectations Influence Effectiveness of SSRIs.” NeuroscienceNews. NeuroscienceNews, 3 October 2017.
<http://neurosciencenews.com/ssri-expectation-7647/>.
Uppsala University (2017, October 3). Expectations Influence Effectiveness of SSRIs. NeuroscienceNews. Retrieved October 3, 2017 from http://neurosciencenews.com/ssri-expectation-7647/
Uppsala University “Expectations Influence Effectiveness of SSRIs.” http://neurosciencenews.com/ssri-expectation-7647/ (accessed October 3, 2017).

Abstract

Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial

Background
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

Methods
We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory – State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

Findings
Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21∙17, 95% CI 10∙69–31∙65, p < 0∙0001) with more than three times higher response rate (50% vs. 14%; χ2(1) = 6∙91, p = 0∙009) and twice the effect size (d = 2∙24 vs. d = 1∙13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3∙68, p ≤ 0∙001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3∙24, p = 0∙0006) and attenuated amygdala (z threshold 2∙70, p = 0∙003) activity.

Interpretation
The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

“Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial” by Vanda Faria, Malin Gingnell1, Johanna Motilla Hoppe, Olof Hjorth, Iman Alaie, Andreas Frick, Sara Hultberg, Kurt Wahlstedt, Jonas Engman, Kristoffer N.T. Månsson, Per Carlbring, Gerhard Andersson, Margareta Reis, Elna-Marie Larsson, Mats Fredrikson, and Tomas Furmark in EBioMedicine. Published online September 26 2017 doi:10.1016/j.ebiom.2017.09.031

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