Investigating the Effects of the Antidepressant Fluoxetine on the Emotional Processing of Young People With Depression - a Double Blind, Placebo-controlled Design fMRI Study

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.