Effects of Acute Ebselen Add-on Treatment on Resting State Function Connectivity in Depressed Patients with Inadequate Response to Antidepressants

Ebselen has been shown to induce a positive emotional processing bias and brain neurochesmistry in healthy volunteers. However, little is known about its effects on resting-state functional connectivity (rs-FC) in depressed patients who show inadequate responses to standard antidepressants. The study aimed to investigate the effect of ebselen as an add-on treatment on rs-FC in this population. We conducted a randomised, double-blind, placebo-controlled trial involving depressed patients who were not responsive to their current treatment. Participants received either ebselen 600 mg twice daily or placebo for seven days. Resting-state functional magnetic resonance imaging was conducted at baseline and on day seven. Resting-state data were analysed using seed-based analysis and independent component analysis. Greater changes in rs-FC between the pregenual anterior cingulate cortex and the cerebellum were observed in ebselen than in placebo, but became negligible after corrections for multiple comparisons. We identified treatment effects within visual networks and between visual and sensorimotor networks, however, these did not survive correction for multiple comparisons. Short-term ebselen treatment in depressed patients with inadequate antidepressant responses did not produce significant changes in rs-FC. These findings may reflect limitations related to the short treatment duration and small and heterogenous sample.