NCT07456501

Brief Summary

Adolescence is a critical developmental period marked by significant social, cognitive, and emotional changes. Unfortunately, it is also a time when the risk of depression and anxiety rises dramatically. Early, effective treatment is essential to mitigate long-term impacts on relationships, education, and life satisfaction. While psychological therapies are recommended as first-line treatment for mild to moderate depression in young people, antidepressant use (particularly SSRIs such as Prozac) has risen sharply, especially among girls aged 15-17. Despite their widespread use, there is limited research on how SSRIs address adolescent depression, leaving clinicians with little evidence to guide treatment decisions. The Fluoxetine and Understanding Social Experiences (FUSE) study aims to shed light on how Prozac (medically known as fluoxetine) influences decision-making in healthy young people in four key areas that are known to be affected by depression: emotional processing (e.g., facial expression recognition), social function (e.g., sensitivity to peer rejection), reward processing (e.g., how people learn from rewards and punishments), and motivation (e.g., how people make decisions about whether a certain outcome or reward is worth the effort to obtain). Some of the tests employed in the study use facial expression and heart-rate recording as aditional measures. We are aiming to recruit and test 80 young people between the ages of 18 and 24. When included in the study, participants are randomly assigned to receive either a weeklong treatment with fluoxetine, or a placebo (a pill with no active ingredients). The study follows a double-blind design, which means that neither the researchers nor the participants are aware of the treatment received so as to not influence the results. We belive that fluoxetine will have beneficial effects on social decision-making in young people, which might manifest as increased accuracy labelling positive facial expressions, less sensitivity to negative feedback, lower self-reported negative mood in response to social exclusion and reduced heart rate/negative facial expressivity in response to unpleasant social experiences. The FUSE study aims to deepen our understanding of how antidepressants affect decision-making in young people, at a time when antidepressant prescriptions have risen but research is scarce. By identifying the exact domains of functioning which are affected by antidepressant use in this age group, this research will help inform which young people are likely to benefit most from drug treatment. The project results will be published in peer-reviewed journals and presented at academic conferences. We are also working with a group of young advisors who will help us decide how to best share our results with others in their age group. A brief summary of the study findings will also be provided to participants who would like to receive it. All research data, excluding information that could identify participants, will be stored safely for at least 10 years after final publication or public release.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for not_applicable

Timeline
13mo left

Started Mar 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress21%
Mar 2026Jul 2027

Study Start

First participant enrolled

March 1, 2026

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

March 2, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 6, 2026

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 20, 2027

Expected
2 days until next milestone

Study Completion

Last participant's last visit for all outcomes

July 22, 2027

Last Updated

March 6, 2026

Status Verified

March 1, 2026

Enrollment Period

1.4 years

First QC Date

March 2, 2026

Last Update Submit

March 2, 2026

Conditions

Keywords

DepressionAdolescent depressionFluoxetineProzacYoung peopleReward processingEffort-based decision-makingSocial cognitionPeer rejection

Outcome Measures

Primary Outcomes (1)

  • Behavioural measure: Facial Expression Recognition Task (FERT)

    Recognition of positive (happy, surprise) faces in the Facial Expression Recognition Task.

    On the last day of the 7-day treatment

Secondary Outcomes (5)

  • Self-report measure: the Need Threat Scale

    On the last day of the 7-day treatment

  • Behavioural measure: Probabilistic Reversal Learning Task

    On the last day of the 7-day treatment

  • Behavioural measure: Piggybank Task

    On the last day of the 7-day treatment

  • Self-report measure: Perception of social rejection on the Verbal Interaction Social Threat (VIST) Task

    On the last day of the 7-day treatment

  • Behavioural measure: Proportion of anger-related solutions found on the Word Completion Task

    On the last day of the 7-day treatment

Other Outcomes (2)

  • Physiological measure: Heart Rate Variability in response to social rejection

    On the last day of the 7-day treatment

  • Physiological measure: Facial Expression in response to social rejection

    On the last day of the 7-day treatment

Study Arms (2)

Fluoxetine

EXPERIMENTAL
Drug: Fluoxetine

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Participants will be taking a 20mg fluoxetine capsule daily for 7 days.

Fluoxetine

Participants will be taking a placebo capsule daily for 7 days.

Placebo

Eligibility Criteria

Age18 Years - 24 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Be aged 18-24 years (inclusive)
  • Be resident in the UK for the duration of the study
  • Have normal or corrected to normal vision
  • Participant is willing and able to give informed consent for participation in the research
  • Sufficiently fluent English to understand and complete the study

You may not qualify if:

  • Psychiatric History:
  • Current or past diagnosis of any psychiatric disorder, as determined by the SCID-5 and self-report. This includes, but is not limited to, depression, anxiety disorders, alcohol or drug dependency, personality disorders, suicidal ideation, and other psychiatric conditions;
  • First degree relative with a diagnosis of mania.
  • Lifestyle:
  • Heavy smoker or vaper (\> 10 cigarettes per day, or \>2 mL e-liquid, or \>15mg/day from a nicotine patch);
  • Heavy use of caffeine (drink \> 4 of 250ml cups/cans of coffee or energy drinks per day);
  • Heavy alcohol drinker (drink \>14 standard alcoholic drinks per week);
  • Current or recent use (in the last 3 months) of any psychoactive substance according to self-report and a urine drug test screening for recent use of 10 common recreational substances.
  • Unable or unwilling to consume gelatine (study capsules will be gelatine-based).
  • Physical Health:
  • Severely underweight or overweight in a manner that renders them unsuitable for the study in the opinion of the study medical advisor;
  • Known contraindication to fluoxetine, such as hypersensitivity to fluoxetine or any component in its formulation;
  • Pregnancy, as determined by a urine pregnancy test or plans to become pregnant within the next 3 months;
  • Breastfeeding.
  • Medical History:
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Oxford Department of Psychiatry

Oxford, OX3 7JX, United Kingdom

Location

Related Publications (1)

  • Murphy SE, Capitao LP, Giles SLC, Cowen PJ, Stringaris A, Harmer CJ. The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action. Lancet Psychiatry. 2021 Sep;8(9):824-835. doi: 10.1016/S2215-0366(21)00154-1.

    PMID: 34419187BACKGROUND

MeSH Terms

Conditions

Depression

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

PropylaminesAminesOrganic Chemicals

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Cognitive Neuroscience

Study Record Dates

First Submitted

March 2, 2026

First Posted

March 6, 2026

Study Start

March 1, 2026

Primary Completion (Estimated)

July 20, 2027

Study Completion (Estimated)

July 22, 2027

Last Updated

March 6, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Data which has been fully de-identified and relevant supporting materials (e.g., study protocol, data dictionary, and analysis documentation) may be shared with other academic organisations in the future, including those outside of the UK and the EU. Participants will be informed of this and specific consent for this will be obtained.

Shared Documents
STUDY PROTOCOL, SAP, ANALYTIC CODE
Time Frame
Data will be available within 6 months of data collection completion (end 2027).
Access Criteria
Fully de-identified individual participant data (IPD) and relevant supporting documentation may be shared with academic researchers for scientific research purposes. Access will be limited to researchers affiliated with recognised academic or research institutions, including those outside of the UK and EU. Approved researchers will be granted access only to fully de-identified IPD and relevant supporting materials. Data will be shared via secure transfer methods or through a controlled-access data repository.

Locations