Fluoxetine and Understanding Social Experiences (FUSE)

Investigating the Effects of Fluoxetine on Reinforcement Learning and Social Cognition in Healthy Young People

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult Participants; Depression in Adolescence; Antidepressant Activity in Healthy Volunteers
• Intervention / Treatment: Drug: Fluoxetine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Harmer; Phone Number: +44 1865 618326; Email: catherine.harmer@psych.ox.ac.uk
• Study Contact Backup: Name: Andreea Raslescu; Phone Number: +44 1865 618245; Email: andreea.raslescu@psych.ox.ac.uk

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7JX
    • University of Oxford Department of Psychiatry
    • Contact: Andreea Raslescu; Phone Number: +44 1865 618245; Email: andreea.raslescu@psych.ox.ac.uk
    • Principal Investigator: Catherine Harmer, DPhil, MA, DipLATHE
    • Sub-Investigator: Susannah Murphy, DPhil
    • Sub-Investigator: Andreea Raslescu, DPhil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

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:

• Past or ongoing health issue which, in the opinion of the study medical advisor, may interfere with the safety of the participant or the scientific integrity of the study. This can include but is not limited to: seizures or epilepsy, abnormal heart rhythm, renal disease, hepatic disease, glaucoma, diabetes, bleeding disorders or clotting conditions (e.g., haemophilia, thrombocytopenia);
• Diagnosis of a significant neurological condition (e.g., epilepsy, multiple sclerosis, traumatic brain injury);
• Current or recent use of medication that might interfere or interact with the effects of fluoxetine, in the opinion of the study medical advisor. This can include but is not limited to: monoamine oxidase inhibitors (MAOIs), medications affecting serotonin levels (e.g., tramadol, triptans, St. John's Wort), anticoagulants or blood thinners (e.g., warfarin), anti-inflammatory medications (e.g., aspirin, ibuprofen), or medications known to affect heart rhythm.

Prior Study Participation:

• Participation in any other psychological or medical experiment involving taking any kind of drug/medication/vaccine, within the last 3 months;
• Participation in any other study involving the current or similar tasks, within the last 6 months.

Other considerations:

•Any other significant finding which may arise during the screening process and which, in the opinion of the Principal Investigator/medical advisor, may influence the scientific integrity of the study, or the participant's safety or ability to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants will be taking a placebo capsule daily for 7 days.
Experimental: Fluoxetine	Drug: Fluoxetine; Participants will be taking a 20mg fluoxetine capsule daily for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-report measure: the Need Threat Scale	Participant scores on the 20-item Need Threat Scale, administered after the Cyberball task (an ostracism paradism). The scale ssesses self-reported current satisfaction levels with belonging, self-esteem, meaningful existence, and control on 7-point scales ranging from 1 (do not agree) to 7 (agree), serving as a proxy of whether these needs are threatened.	On the last day of the 7-day treatment
Behavioural measure: Probabilistic Reversal Learning Task	Performance on a probabilistic reversal learning task, in which participants learn probabilistic reward contingencies associated with three stimulus images, and them must relearn when those contingencies are reversed.	On the last day of the 7-day treatment
Behavioural measure: Piggybank Task	Performance on a task measuring action vigour, where participants have to earn monetary rewards by pressing keys to "shake" coins from virtual piggy banks. Piggybanks vary in effort and reward, requiring ongoing adjustment.	On the last day of the 7-day treatment
Self-report measure: Perception of social rejection on the Verbal Interaction Social Threat (VIST) Task	In the Verbal Interaction Social Threat Task, participants are led to believe they will be engaging in an online interaction with two other study participants. Participants are shown a series of prompts and, for each one, choose one of four possible "icebreaker" sentences (for example, under the theme of sport: "I play a team sport such as football, rugby or netball" or "I play an individual sport like tennis or athletics"). After each choice, they receive responses that appear to be typed in real time by the two peers. In reality, these responses are pre-programmed and skewed toward negative feedback for most prompts (e.g., a peer might reply "I think team sports are more like a game than a real sport"). Following each exchange, participants rate how positively or negatively they perceived the interaction.	On the last day of the 7-day treatment
Behavioural measure: Proportion of anger-related solutions found on the Word Completion Task	In this task, participants complete word puzzles with multiple solutions, many allowing aggression-related words (e.g., k n _ _ _ as "knees" or "knife"). It follows the VIST rejection paradigm, which is expected to reduce social cohesion and increase anti-social thought.	On the last day of the 7-day treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological measure: Heart Rate Variability in response to social rejection	Heart rate variability measures across tasks inducing social rejection.	On the last day of the 7-day treatment
Physiological measure: Facial Expression in response to social rejection	Video recordings that identify facial expressions across tasks inducing social rejection.	On the last day of the 7-day treatment

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Wellcome Trust; Oxford Health Biomedical Research Centre (OH BRC) support scheme

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): July 20, 2027
• Study Completion (Estimated): July 22, 2027

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Fluoxetine; Social cognition; Prozac; Adolescent depression; Young people; Reward processing; Effort-based decision-making; Peer rejection
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Organic Chemicals; Amines; Propylamines; Fluoxetine
• Other Study ID Numbers: MS IDREC 2337721

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data will be available within 6 months of data collection completion (end 2027).
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No