Rapid clinical and EEG microstate changes 24 h after intranasal esketamine in major depressive disorder with suicidal ideation: a prospective paired study.

Abstract

<h4>Background</h4>Major depressive disorder (MDD) with suicidal ideation constitutes a psychiatric emergency that requires rapid symptom relief. Intranasal esketamine can reduce depressive symptoms within hours, yet the earliest brain-level correlates of response remain insufficiently characterized.<h4>Methods</h4>A total of 31 patients with major depressive disorder and suicidal ideation or behavior were enrolled in this prospective study. Patients hospitalized for MDD with suicidal ideation received intranasal esketamine in addition to standard care. Clinical scales and resting-state EEG were obtained before the first dose (T0) and 24 h later (T1). The primary clinical outcomes were HAMD-17 scores. EEG analyses included whole-brain relative power spectral density (PSD) and microstate parameters based on a seven-class template. After quality control, 24 patients had qualified resting-state EEG data, 23 had qualified paired questionnaire data, and 18 had complete matched EEG and questionnaire data for integrated analyses.<h4>Results</h4>Depressive symptoms improved significantly within 24 h. HAMD score decreased from 25.32 ± 1.37 to 20.55 ± 1.52 in paired complete cases (n = 22; FDR = 0.0016). In contrast, PSD did not change significantly across delta, theta, alpha, beta, or gamma bands. Microstate analysis identified significant early changes, especially in the occurrence and coverage of microstate D, together with altered transition patterns among several microstate classes.<h4>Conclusions</h4>Intranasal esketamine was associated with rapid clinical improvement in depressive symptoms over 24 h. Compared with conventional PSD indices, EEG microstate metrics appeared more sensitive to early treatment-related network reconfiguration and may provide candidate short-term electrophysiological readouts of rapid treatment response.

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