The Antidepressant Advisor (Study 3): fMRI Study to Predict Treatment Response in Patients With Depression

This prospective observational study (ADeSS-Study3) investigates candidate biomarkers prospectively predicting response to antidepressant medications and prognosis in major depressive disorder (MDD). Currently, about half of MDD patients will not respond to the first course of selective serotonin reuptake inhibitors (SSRIs), while more than 40% will also not achieve remission after a second round of another SSRI. There are functional magnetic resonance imaging (fMRI) measures in several brain regions, showing clinical potential as predictors of response and non-response to SSRIs. The overall aim of the study is to identify the neural signatures prospectively predicting poor prognosis in MDD patients after receiving four months of treatment in UK primary care. Specifically, it looks to evaluate four fMRI measures: 1) self-blame-selective subgenual cortex and ventral striatum connectivity with the right anterior temporal lobe; 2) pregenual anterior cingulate cortex activity in response to implicit emotional facial expressions; 3) amygdala activation in response to implicit emotional facial expressions; and 4) subgenual cingulate seed-based resting state. In addition, a more specific objective of the study is to provide the proof-of-concept for using fMRI to prospectively predict which MDD patients will not benefit from SSRI antidepressant treatments in UK primary care. The long-term translational aim is to identify such patients and provide them with alternative treatments without delay by informing a decision support system with the information provided by these candidate biomarkers. This study is linked to the Antidepressant Advisor Trial (ADeSS-Study 1: NCT03628027), in which the feasibility is evaluated of a novel computerised decision support system for antidepressant prescribing in MDD patients in a UK primary care setting.