Antidepressant Activity in Healthy Volunteers, Depression in Adolescence, Healthy Adult Participants
Conditions
Keywords
Depression, Adolescent depression, Fluoxetine, Prozac, Young people, Reward processing, Effort-based decision-making, Social cognition, Peer rejection
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.
Interventions
DRUGFluoxetine
Participants will be taking a 20mg fluoxetine capsule daily for 7 days.
DRUGPlacebo
Participants will be taking a placebo capsule daily for 7 days.
Sponsors
University of Oxford
Wellcome Trust
Oxford Health Biomedical Research Centre (OH BRC) support scheme
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 24 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Behavioural measure: Facial Expression Recognition Task (FERT) | On the last day of the 7-day treatment | Recognition of positive (happy, surprise) faces in the Facial Expression Recognition Task. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Self-report measure: the Need Threat Scale | On the last day of the 7-day treatment | 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. |
| Behavioural measure: Probabilistic Reversal Learning Task | On the last day of the 7-day treatment | 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. |
| Behavioural measure: Piggybank Task | On the last day of the 7-day treatment | 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. |
| Self-report measure: Perception of social rejection on the Verbal Interaction Social Threat (VIST) Task | On the last day of the 7-day treatment | 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. |
| Behavioural measure: Proportion of anger-related solutions found on the Word Completion Task | On the last day of the 7-day treatment | 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. |
Countries
United Kingdom
Contacts
CONTACTCatherine Harmer
CONTACTAndreea Raslescu
Outcome results
None listed