Fluoxetine on Emotional Experience (FLEX) Study (FLEX)

The Effect of Fluoxetine Treatment on Anger Processing in Healthy Young People

The goal of this clinical medicine study is to investigate how does antidepressant fluoxetine modulate anger processing in healthy young people . The main questions it aims is to answer are:

1. How does fluoxetine affect responses to anger-related stimuli such as words, faces, and autobiographical recall?
2. How does fluoxetine influence responses during frustration induction in frustrative non-reward and threat paradigms?
3. Does the effect manifest in physiological markers, including heart rate variability and facial expressions?

Researchers will compare fluoxetine to a placebo to see if drug fluoxetine affects anger processing.

Participants will:

Take 20mg fluoxetine or a placebo every day for 7 days. Visit the university site for questionnaire and tasks assessments. Heart rate variability and facial expressions will be recorded in some of the tasks.

Study Overview

• Status: Recruiting
• Conditions: Depression; Irritability; Depression - Major Depressive Disorder
• Intervention / Treatment: Drug: Fluoxetine; Drug: Placebo

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

Contacts and Locations

• Study Contact: Name: Catherine Harmer, PhD; Phone Number: +441865 618326; Email: catherine.harmer@psych.ox.ac.uk
• Study Contact Backup: Name: Ye Wo, MSc; Phone Number: +447564300004; Email: ye.wo@psych.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7JX
      • Recruiting
      • Department of Psychiatry, University of Oxford
      • Contact: Ye Wo, MSc; Phone Number: 07564300004; Email: ye.wo@psych.ox.ac.uk

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:

The participant may not enter the study if ANY of the following apply:

Psychiatric History:

• Current or past diagnosis of any psychiatric disorder, as determined by the Structured Clinical Interview for the DSM-5 (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 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;

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;
• Not able to consume gelatine;

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, including but not limited to: seizures or epilepsy, heart rhythm problem, 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).
• Diagnosis of a neurodevelopmental condition, such as autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD);
• Current or recent use of medication that might interfere or interact with the effects of fluoxetine, in the opinion of the study medical advisor, including but 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;

Others

•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 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
Active Comparator: fluoxetine; Participants will be taking 20mg fluoxetine daily.	Drug: Fluoxetine; Participants will receive 20mg of fluoxetine daily for 7 days. Tablets encapsulated to aid blinding.
Placebo Comparator: placebo; Participants will be taking one placebo capsule daily.	Drug: Placebo; Participants will receive one dose placebo (sucrose) daily for 7 days. Tablets encapsulated to aid blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral Measure: Facial Expression Recognition Task (FERT)	Recognition of angry 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
Behavioural Measure: The Affordances Task	Performance on an affordances task in which participants have to decide to fight or escape under threatening situations with different environmental affordance conditions.	On the last day of the 7-day treatment
Behavioural Measure: Emotional Categorization Task (ECAT)	Performance on recognising and memorising anger related words in the Emotional Categorization Task (ECAT)	On the last day of the 7-day treatment.
Performance on Carnival Task	Performance on an anger induction task in which the study's rigged design creates frustrating non-reward responses.	On the last day of the 7-day treatment.
Subjective Measure: Rest Task	Participants' rating of anger-related emotions during a resting task.	On the last day of the 7-day treatment.
Subjective Measure: Anger Memory Recall Task	Participants' ratings of anger-related emotions and bodily sensations during a task that involves guided imagery of a past personal experience.	On the last day of the 7-day treatment.
Physiological Measure: Heart Rate Variability	Heart rate variability measures across a battery of anger-induction tasks.	On the last day of the 7-day treatment.
Physiological Measure: Facial Expression	Video recordings that identify facial expressions across a battery of anger-induction tasks.	On the last day of the 7-day treatment.
Behavioural measure: Emotional Recognition Memory Task (EMEM)	Description: Performance on recognising and memorising anger related words in the Emotional Recognition Memory Task (EMEM).	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

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: depression; irritability; young people; fluoxetine; anger
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Organic Chemicals; Amines; Propylamines; Fluoxetine
• Other Study ID Numbers: MS IDREC 1017147

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 to this is obtained within the Informed Consent Form.
• IPD Sharing Time Frame: Data will be available in a few months after all data has been completed (ETA Oct 2026), unblinding has occurred (ETA Dec 2026), and all data analyses has been completed (Dec 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