Functional connectivity (FC) plays a critical role in understanding major depressive disorder (MDD) and treatment mechanisms. Altered FC patterns, particularly within the default mode network (DMN), have been associated with MDD symptoms and therapeutic outcomes. This study systematically reviews the literature on Escitalopram, a selective serotonin reuptake inhibitor (SSRI) with a particular receptor profile, in relation to FC in MDD. A systematic review was conducted using three databases: PubMed, Scopus, and Web of Science. Eleven articles meeting the inclusion criteria were categorized into two groups: treatment effects (six studies) and treatment response prediction (five studies). The six treatment effect studies included 198 patients with MDD and 219 control participants: 205 healthy controls and 14 placebo-treated patients. These studies highlighted Escitalopram’s ability to normalize baseline FC disruptions (hypo- or hyperconnectivity), particularly in DMN subsystems. The five treatment prediction studies examined 159 MDD patients, 97 healthy controls, 22 placebo-treated individuals, and 56 non-responders. Poor treatment efficacy was linked to baseline hypoconnectivity in the dorsolateral prefrontal cortex and altered connectivity between the DMN and the frontoparietal network. Overall, Escitalopram treatment appears to restore FC by normalizing both hyperconnectivity and hypoconnectivity patterns associated with MDD, suggesting a rebalancing of network dynamics underlying symptom improvement. Normalization of altered FC patterns after treatment and associations between baseline FC and treatment response suggest FC’s potential as a biomarker for understanding and predicting SSRI efficacy.
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