Fluoxetine and Understanding Social Experiences

Official title

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

Overview

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.

Interventions

• Drug Fluoxetine
  Participants will be taking a 20mg fluoxetine capsule daily for 7 days.
• Drug Placebo
  Participants will be taking a placebo capsule daily for 7 days.

Primary outcome measures

• Behavioural measure: Facial Expression Recognition Task (FERT) [Time frame: On the last day of the 7-day treatment]

Secondary outcome measures (5)

• Self-report measure: the Need Threat Scale [Time frame: On the last day of the 7-day treatment]
• Behavioural measure: Probabilistic Reversal Learning Task [Time frame: On the last day of the 7-day treatment]
• Behavioural measure: Piggybank Task [Time frame: On the last day of the 7-day treatment]
• Self-report measure: Perception of social rejection on the Verbal Interaction Social Threat (VIST) Task [Time frame: On the last day of the 7-day treatment]
• Behavioural measure: Proportion of anger-related solutions found on the Word Completion Task [Time frame: On the last day of the 7-day treatment]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Basic science

Study locations

United Kingdom · 1 center

• University of Oxford Department of Psychiatry — Oxford

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. PMID 34419187

Identifiers

NCT: NCT07456501 · MS IDREC 2337721

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗