Review: The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression

Functional magnetic resonance imaging (fMRI) can identify brain areas linked to depression symptoms and potential treatment targets. A review of fMRI studies on selective serotonin reuptake inhibitors (SSRIs) and ketamine found that both conventional and fast-acting antidepressants normalize amygdala hyperactivity in response to negative emotional stimuli, suggesting a common pathway for antidepressant action. Ketamine's rapid effects on brain activity and connectivity also trend toward normalizing depression-related abnormalities. While fMRI shows promise for identifying treatment targets, improved methodology and study design are needed before its findings can be used as primary clinical trial outcomes.

Study at a glance

Abstract

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to examine neural responses with and without the use of a functional task. Indeed, fMRI has been used in clinical trials and pharmacological research studies. In mental health, it has been used to identify brain areas linked to specific symptoms but also has the potential to help identify possible treatment targets. Despite fMRI's many advantages, such findings are rarely the primary outcome measure in clinical trials or research studies. This article reviews fMRI studies in depression that sought to assess the efficacy and mechanism of action of compounds with antidepressant effects. Our search results focused on selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed treatments for depression and ketamine, a fast-acting antidepressant treatment. Normalization of amygdala hyperactivity in response to negative emotional stimuli was found to underlie successful treatment response to SSRIs as well as ketamine, indicating a potential common pathway for both conventional and fast-acting antidepressants. Ketamine's rapid antidepressant effects make it a particularly useful compound for studying depression with fMRI; its effects on brain activity and connectivity trended toward normalizing the increases and decreases in brain activity and connectivity associated with depression. These findings highlight the considerable promise of fMRI as a tool for identifying treatment targets in depression. However, additional studies with improved methodology and study design are needed before fMRI findings can be translated into meaningful clinical trial outcomes.