Several magnetic resonance imaging (MRI) findings suggest the role of cortical connectivity treatments in the treatment and selectivity for major depressive disorder (MDD). However, its clinical utility remains to be limited. Recent advancements like electroencephalography (EEG) have made treatment selection easier. This study aims to determine if EEG connectivity can reveal antidepressant neural moderators.

This nonprespecified secondary analysis of a randomized clinical trial included a total of 221 outpatients aged 18-65 years with MDD who were not taking any medication for depression. The patients were assigned to receive either sertraline hydrochloride, a selective serotonin reuptake inhibitor (SSRI), or a placebo. The primary outcome of the study was the identification of pretreatment connectivity treatments.

After correcting for several comparisons, the researchers conducted connectome-wide analyses to reveal that there were moderations by connections within widespread cortical regions for both antidepressants and placebo groups. Using greater alpha-band and lower-gamma band connectivity, the researchers found the placebo to have better outcomes and antidepressants to have the worst outcomes.

The research confirmed the effectiveness of EEG-based network functional connectivity analyses for drawing differences between response to antidepressants and the placebo. The findings also suggested the need for establishing a placebo signature in clinical trials.