OxSYPan: Oxford Study With Young People on Antidepressants
Condition: Depression
MeSH terms: Depression
Study type: Interventional

Summary: 
      Fluoxetine is commonly used to treat adolescent depression, but the neural mechanisms
      underlying antidepressant drugs in the young brain are still poorly understood. This study
      proposes to investigate the effects of a single dose of fluoxetine on emotional neural
      processing in a sample of depressed adolescents, using functional Magnetic Resonance Imaging
      (fMRI).
    

Detailed description: 
      Depression is common in adolescence and is associated with a high risk of suicide.
      Clinically, the presentation of depression in young people is largely similar to the symptoms
      seen in adulthood, although depressed youth may exhibit increased irritability rather than
      (or in addition to) low mood. Therefore, irritability is included as a cardinal symptom in
      the diagnosis of Major Depressive Disorder (MDD) among children and adolescents but not
      adults (American Psychiatric Association, 2013).

      Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat
      adolescent depression, and is the only medication approved for use to treat this disorder in
      the United Kingdom (UK). In the United States (US), fluoxetine is also the drug of choice,
      together with escitalopram. However, our current understanding of the mechanisms underlying
      antidepressant action in adolescents and young people is poor, despite the pressing need to
      explain the complex patterns of clinical response to pharmacotherapy in this group.

      In this randomised, placebo-controlled experimental medicine study, the investigators propose
      to use fMRI to investigate the early effects of fluoxetine in a sample of depressed
      adolescents who have been prescribed fluoxetine by their psychiatrist for the treatment of
      depression. Immediately after being referred to the study team, participants will be
      randomised to take their first dose of either fluoxetine or placebo within the study, and 6
      hours later, they will undergo a neuroimaging scan.

      Previous research from our group showed that a single dose of fluoxetine reduced the accuracy
      to detect angry facial expressions in a group of young healthy volunteers, aged 18 to 21
      (Capitão et al., 2015). Given the key role of anger in the clinical presentation of
      adolescent depression, the reduction in anger perception following fluoxetine highlights a
      potential mechanism through which this antidepressant drug may exert its clinical action.
      However, this hypothesis remains to be investigated in depressed adolescents.

      This study therefore proposes to investigate the acute effects of fluoxetine vs. placebo on
      emotional neural processing, specifically in response to angry faces, in a sample of
      adolescents with MDD. A secondary aim is to investigate the effects of fluoxetine on
      emotional regulation, as well as on resting-state functional connectivity.

      To the extent of the investigators' knowledge, this is the first study to explore the acute
      neural effects of fluoxetine in depressed adolescents. This design is thought to be of high
      value as patients will be referred to the study immediately after being prescribed
      fluoxetine, therefore allowing the investigators to scan them on the day that they take their
      first dose of 10 mg fluoxetine or placebo, administered within the study. Patients will then
      start their antidepressant treatment as prescribed and managed by their treating
      psychiatrist. This unique time window for testing allows the investigation of the effects of
      fluoxetine using a placebo control, and without the ethical concerns associated with
      long-term antidepressant drug studies. This single dose design also enables the
      characterisation of the effects of fluoxetine at a time where changes in mood are not yet
      apparent. Indeed, the few neuroimaging studies conducted to date with depressed adolescents
      are limited by the absence of a placebo control and the measurement of neural changes after
      relatively prolonged treatments (8 weeks). Concurrent changes in symptoms make it difficult
      to determine whether fluoxetine has a direct effect on relevant neural regions or whether the
      antidepressant-induced changes in activity are an indirect consequence of mood improvement.
      The current study design overcomes these constraints.

      The knowledge attained from this study will hopefully help increase our understanding of the
      early mechanisms underlying fluoxetine use in depressed adolescents.
    

Intervention name(s): Fluoxetine; Peppermint syrup
Intervention type(s): Drug; Other
Intervention description(s): Fluoxetine 10 mg/2.5 ml mixed with water; Liquid peppermint syrup measured to the equivalent volume and mixed with water
Other intervention name(s): Prozac
Intervention MeSH terms: Fluoxetine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other