Plain English Summary

Background and study aims
Serotonin is identified as one of the causes and treatments of anxiety disorders like social anxiety disorder. A group of drugs called selective serotonin reuptake inhibitors (SSRIs) is often recommended as first treatment for this condition. However we do not know how SSRIs work and SSRIs have rarely been studied in neuroimaging studies. The aims of the present study are to examine changes in brain activation patterns, brain connectivity, brain structure and neural responses in participants taking SSRIs for social anxiety disorder.

Who can participate?
A total of 48 individuals, men and women between 18-65 years old, suffering from social anxiety disorder according to structured clinical interviews, will be included.

What does the study involve?
All participants will undergo brain scanning before and after a nine week treatment period. During some of these scans, participants will be exposed to emotionally relevant tasks, like viewing slides of faces with different emotional expressions, while their brain activity is being recorded with fMRI (functional magnetic resonance imaging). Other scans will involve measurements of the serotonin and dopamine transporter proteins of the brain using PET (positron emission tomography). These brain scans will then be repeated after drug treatment with either SSRIs or a dummy drug for social anxiety disorder (called placebo). Participants will be randomly allocated to one of these two treatments. After the drug treatment period, and after brain scanning, all participants will be offered additional treatment with cognitive behaviour therapy (CBT). This is a 9 week structured form of psychotherapy focusing on thoughts and behaviours that are problematic for people suffering from social anxiety disorder.

What are the possible benefits and risks of participating?
Benefits include free treatment of a potentially serious anxiety condition. Participants also receive a small sum of money (approximately 380 USD). The risks involved are minimal, with the benefits far outweighing the risks. During PET scans, participants are exposed to radioactive material, but in low doses that do not affect normal bodily functions. Pregnant or breastfeeding women will not be included. There are also safety issues regarding MRI/fMRI scans, i.e. individuals who have metallic materials within the body may not be allowed to participate. Also individuals who have heart pacemakers or have underwent surgery of the heart or head may not participate. There may be unwanted side effects such as nausea or diminished libido from the study drugs, although previous research indicates that they are generally well tolerated.
Where is the study run from?
The study is run from Department of Psychology, Uppsala university, Sweden.

When is the study starting and how long is it expected to run for?
It is expected that the study will start in mid-March 2014 (recruitment, initial neuroimaging, treatment) for the 24 participants while the remaining 24 participants will be assessed and treated during the autumn of 2014. A one year follow-up (with questionnaires) will be conducted. The study is expected to be completed by December 2015.

Who is funding the study?
Funding has been provided by the Swedish Council of Health, Working Life and Welfare; the Swedish Foundation for Humanities and Social Sciences; and the Swedish Research Council.

Who is the main contact?
Professor Tomas Furmark
tomas.furmark@psyk.uu.se

Trial website

http://www.sfstudie.se

Contact information

Type

Scientific

Primary contact

Prof Tomas Furmark

ORCID ID

Contact details

Department of Psychology
Uppsala University
Box 1225
Uppsala
SE-75142
Sweden
tomas.furmark@psyk.uu.se

Additional identifiers

EudraCT number

2013-002962-38

ClinicalTrials.gov number

Protocol/serial number

TF2013

Study information

Scientific title

Mechanisms of action of selective serotonin reuptake inhibitor (SSRI) pharmacotherapy for social anxiety disorder: a randomised neuroimaging trial

Acronym

Study hypothesis

It is hypothesised that treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram will alleviate social anxiety accompanied by attenuated neural responsiveness to emotional challenges in limbic brain regions including the amygdala and insula cortex. The study further evaluates, with exploratory analyses, how SSRI treatment of social anxiety disorder affects:
1. Functional brain connectivity between the amygdala and prefrontal cortex
2. Brain structure, i.e. gray matter volume and white matter integrity
3. Brain monoaminergic processes, i.e. serotonin and dopamine reuptake efficiency
It is also examined how monoamine-related gene variants influence the brain parameters above.

Ethics approval

Regional Research Ethics Committee, Uppsala, ref. 2013/184

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

http://www.sfstudie.se/#tabs-3

Condition

Social anxiety disorder (social phobia)

Intervention

Patients with social anxiety disorder will be randomised into one of two treatment conditions: Escitalopram 20 mg or active placebo. All other therapies will be avoided.

1. Administration of escitalopram, 1 tablet daily, is based on the accepted recommended dose 10 mg per day during the first week and 20 mg per day for the rest of the treatment period. Participants are informed that this drug has been effective in previous controlled trials.
2. Active placebo is administered with a similar capsule. Participants are informed that it is a neurokinin-1 receptor antagonist lacking the crucial anxiolytic substance, and hence that it has been ineffective in previous controlled trials.

The treatment period is 9 weeks (63 days). Participants have an extra drug supply for another 14 days because the day of the last neuroimaging assessment may vary (hence treatment could be prolonged for maximum 14 days). Participants will undergo neuroimaging assessment with fMRI (n=48) and PET (n=24) before and after the 9 week treatment period. After the initial 9 week treatment period and neuroimaging assessments, all participants are offered Internet-delivered Cognitive Behavior Therapy (ICBT) for an additional 9 week period. This ICBT treatment is optional. The ICBT program has been found efficacious in several previous trials. Follow-up assessment (questionnaires) will be conducted after one year.

Intervention type

Drug

Phase

Not Applicable

Drug names

Escitalopram

Primary outcome measures

1. The Liebowitz Social Anxiety Scale (LSAS)
2. Spielberger state anxiety inventory (STAI-S) during anticipatory anxiety in the fMRI-setting

Primary measures will be administered at 4 times: 1. baseline, 2. posttreatment after nine weeks of drug treatment, 3. after nine weeks of additional (voluntary) cognitive behaviour therapy, and 4. at 12 month follow-up

Secondary outcome measures

1. The Clinical Global Impression – Improvement (CGI-I) scale
2. Social Interaction Anxiety Scale (SIAS)
3. Social Phobia Scale (SPS)
4. Social Phobia Screening Questionnaire (SPSQ)
5. Montgomery-Åsberg Depression Rating Scale (MADRS-S)
6. Beck Anxiety Inventory (BAI)
7. Quality of Life Inventory (QOLI)
8. Karolinska scale of personality (KSP)
9. NEO-PI-R, personality inventory
10. Spielberger trait anxiety inventory (STAI-T)

Secondary measures will be administered at 4 times: 1. baseline, 2. posttreatment after nine weeks of drug treatment, 3. after nine weeks of additional (voluntary) cognitive behaviour therapy, and 4. at 12 month follow-up

Overall trial start date

15/03/2014

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Social anxiety disorder (social phobia), according to DSM-5, must be the main diagnosis as assessed with the structured clinical interview for DSM disorders (SCID)
2. Otherwise somatically healthy
3. Age 18-65, but not postmenopausal
4. Willingness to participate in a symptom provocation brain imaging trial

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

48 individuals diagnosed with social anxiety disorder

Participant exclusion criteria

1. Treatment of social anxiety within the three months preceding the study
2. Current serious or dominant psychiatric disorder other than social anxiety disorder (e.g. psychosis, major depressive disorder, bipolar disorder)
3. Suicidal ideation
4. Chronic use of prescribed medication that could influence the results (e.g. other anxiolytic or antidepressant drugs, certain hypnotics or herbs like St John’s Wort)
5. Abuse of alcohol or narcotics
6. Pregnancy or planned pregnancy during the study period
7. Menopause
8. Previous positron emission tomography (PET) examination
9. Contraindications for MRI investigation (e.g. implants or other metal objects in the body, brain and heart operations)

Recruitment start date

15/03/2014

Recruitment end date

31/12/2015

Locations

Countries of recruitment

Sweden

Trial participating centre

Department of Psychology
Uppsala
SE-75142
Sweden

Sponsor information

Organisation

Uppsala University (Sweden)

Sponsor details

c/o Tomas Furmark
Department of Psychology
Box 1225
Uppsala
SE-75142
Sweden

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

The Swedish Council of Health, Working Life and Welfare (FORTE) (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Swedish Foundation for Humanities and Social Sciences (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Swedish Research Council (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Editorial Notes