The Effect of SSRIs on Threat of Shock Potentiated Neural Circuitry

NCT07074652 | Completed

• 1 other identifier: 6198/002
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to increase the knowledge about psychological processes which may contribute to mental health problems such as depression and anxiety. This study aims to investigate if administering Escitalopram, an antidepressant which increases serotonin levels in parts of the brain, affects how the brain processes emotional information. It is hoped that measuring these changes will increase the understanding of processes involved in mental health problems.

Conditions

Anxiety

Keywords

anxiety; selective serotonin reuptake inhibitor; emotion; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• 'Aversive amplification circuit' connectivity

  The engagement of the neural circuit of the amygdala, cingulate cortex and prefrontal cortex will be measured via an fMRI analysis technique called a psychophysiological interactions (PPI) analysis. PPI analysis concerns behaviour-specific increases in the relationship across regional brain activity - this means that it can allow one to assess whether two regions (a priori selected ROIs) show increased connectivity during a specific context or behaviour, suggesting a behaviour-specific increase in transfer of information. The output of this analysis will take form of a continuous beta weight - an index of connectivity across two brain regions (amygdala and medial prefrontal cortex), which represents the primary outcome of the study.

  Baseline and 2-3 weeks after baseline

Secondary Outcomes (16)

• Cognitive task performance: Loss/risk aversion task

  Baseline and 2-3 weeks after baseline

• Cognitive task performance: Go/no-go task

  Baseline and 2-3 weeks after baseline

• Cognitive task performance: Facial emotional processing task

  Baseline and 2-3 weeks after baseline

• Cognitive task performance: Emotional face recognition task

  Baseline and 2-3 weeks after baseline

• Cognitive task performance: Visual affective bias task

  Baseline and 2-3 weeks after baseline

Study Arms (4)

Healthy Control - Escitalopram

ACTIVE COMPARATOR

Participants took 10mg escitalopram for 2-3 weeks, once daily. Escitalopram was administered in the form of a tablet, manufactured and donated for research by Lundbeck (tablet core: microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, talc, magnesium stearate; tablet coating: hypromellose 6cP, titanium dioxide (E171), macrogol 6000). Exact length of administration was dependent on participants' availability to attend their second scan.

Drug: Escitalopram

Healthy Control - Placebo

PLACEBO COMPARATOR

Participants took a placebo tablet for 2-3 weeks, once daily. Placebo was administered in the form of a tablet, manufactured and donated for research by Lundbeck and matching the escitalopram tablet given to the other study groups in colour and size. Exact length of administration was dependent on participants' availability to attend their second scan.

Drug: Placebo

Anxious Individuals - Escitalopram

EXPERIMENTAL

Participants took 10mg escitalopram for 2-3 weeks, once daily. Escitalopram was administered in the form of a tablet, manufactured and donated for research by Lundbeck (tablet core: microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, talc, magnesium stearate; tablet coating: hypromellose 6cP, titanium dioxide (E171), macrogol 6000). Exact length of administration was dependent on participants' availability to attend their second scan.

Drug: Escitalopram

Anxious Individuals - Placebo

PLACEBO COMPARATOR

Participants took a placebo tablet for 2-3 weeks, once daily. Placebo was administered in the form of a tablet, manufactured and donated for research by Lundbeck and matching the escitalopram tablet given to the other study groups in colour and size. Exact length of administration was dependent on participants' availability to attend their second scan.

Drug: Placebo

Interventions

Escitalopram DRUG

Participants received 2-3 weeks of escitalopram.

Anxious Individuals - Escitalopram; Healthy Control - Escitalopram

Placebo DRUG

Participants received 2-3 weeks of placebo, matched in colour and size to the escitalopram.

Anxious Individuals - Placebo; Healthy Control - Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Controls:
• Fluency in English
• Registration with a UK General Practitioner
• Capacity for consent
• No personal history of long-term medical conditions or psychiatric illness (including substance dependence, assessed with the Mini International Neuropsychiatric Interview)
• Anxious Individuals:
• Fluency in English
• Registration with a UK General Practitioner
• Capacity for consent
• Meeting criteria for generalised anxiety disorder, panic disorder and/or agoraphobia (also assessed with the Mini International Neuropsychiatric Interview); permitted comorbid conditions were: major depressive disorder, obsessive-compulsive disorder and/or post-traumatic stress disorder

You may not qualify if:

• Healthy Controls and Anxious Individuals:
• Having consumed alcohol within 12 hours prior to the study
• having used illicit drugs within 3 months prior to the study
• Having had any contraindications to MRI scanning
• Being pregnant or breastfeeding
• Having had impaired or uncorrected vision or hearing

Sponsors & Collaborators

• UCLH/UCL Joint Research Office: lead
• University College, London: collaborator

Study Sites (1)

University College London

London, United Kingdom

Location

Related Publications (2)

• Lukow PB, Lowther M, Pike AC, Yamamori Y, Chavanne AV, Gormley S, Aylward J, McCloud T, Goble T, Rodriguez-Sanchez J, Tuominen EW, Buehler SK, Kirk P, Robinson OJ. Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study. J Psychopharmacol. 2024 Dec;38(12):1071-1082. doi: 10.1177/02698811241286773. Epub 2024 Oct 4.

  PMID: 39364684 BACKGROUND

• Lukow PB, Lowther M, Pike AC, Yamamori Y, Chavanne AV, Gormley S, Aylward J, Vera CE, McCloud T, Goble T, Rodriguez-Sanchez J, Tuominen EW, Buehler SK, Kirk P, Robinson OJ. Brain activation and connectivity after 2-3 weeks of escitalopram administration in anxiety disorders: A randomised trial. J Affect Disord. 2026 Feb 1;394(Pt B):120682. doi: 10.1016/j.jad.2025.120682. Epub 2025 Nov 13.

  PMID: 41241072 DERIVED

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2025
• First Posted: July 20, 2025
• Study Start: December 1, 2017
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)