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Esketamine combined with sertraline for brain altered regional homogeneity in patients with major depressive disorder: A preliminary study.

Xiang Liu, Ziyi Hua, Yongqiang Shu, Lifeng Li, Shan Xia, Jiangping Li, Haijun Li, Ailan Wan, Dechang Peng, Guojiang Wu

Brain Research Bulletin November 13, 2025 DOI: 10.1016/j.brainresbull.2025.111637 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 27
Population Patients with major depressive disorder and healthy individuals
Interventions esketamine sertraline
Dose 0.25 mg/kg
Duration 2-week intervention
Topics Depression Esketamine
Keywords Antidepressants Reho Sertraline Clinical depression Mood disorder Mental health Antidepressant therapy Pharmacotherapy Drug treatment Medication Psychopharmacology Combination therapy Brain activity Neuroimaging Brain function Regional homogeneity
Citations 1
Key findings After two weeks of esketamine combined with sertraline, the left middle temporal gyrus showed a reversal of abnormal regional homogeneity toward normal levels, and these changes correlated with anxiety scores.

Abstract

This study aims to explore the relationship between the antidepressant effects of drugs (esketamine combined with sertraline) and brain function changes in patients with major depressive disorder. A total of 27 patients with major depressive disorder (MDD) and 27 healthy individuals were included in the study. All MDD patients received a 2-week course of intravenous esketamine infusion (0.25 mg/kg) combined with sertraline. We assessed patients' post-treatment emotional and cognitive recovery using the Hamilton Anxiety Scale, Hamilton Depression Scale, Beck Suicide Ideation Scale, and Montreal Cognitive Assessment Scale. Additionally, all participants underwent magnetic resonance imaging (MRI) scans, with local consistency techniques employed to evaluate changes in brain spontaneous activity before and after treatment. Finally, correlation analysis was used to assess the relationship between the characteristics of spontaneous brain activity in MDD patients and clinical scales. We found that the Reho values of certain brain regions in MDD patients differed from those in the healthy group, primarily manifested as increased regional homogeneity (Reho) values in the right superior frontal gyrus, right precentral gyrus, right middle occipital gyrus, and left middle temporal gyrus; and decreased Reho values in the right middle temporal gyrus, bilateral temporal lobes, and right posterior cerebellar lobe. After two weeks of drug treatment, we observed a reversal in the local consistency of the left middle temporal gyrus (L-MTG), which tended toward normal levels. Additionally, we observed significant improvements in anxiety, depression symptoms, suicidal ideation, and MoCA scores in MDD patients post-treatment. Furthermore, changes in Reho values in the left middle temporal gyrus (L-MTG) were significantly correlated with scores on clinical assessment scales (HAMA). Patients with MDD exhibit imbalances in spontaneous brain activity. The L-MTG, as a key hub of the default mode network and salience network, is associated with the severity of depression and recovery after treatment.

Comparable studies

Other observational and cohort studies on esketamine for depression, most cited first.

Study Year Design Participants
Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression Patients with treatment-resistant bipolar depression (B-TRD) and unipolar... 2023 Observational cohort n = 70
Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. Adults with treatment-resistant depression 2023 Observational study n = 62
Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) Treatment-resistant depression patients 2023 Retrospective, multicentric, real-world study n = 149
Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study Patients with treatment-resistant depression and a substance use disorder 2023 Observational, retrospective, multicentre study n = 26
Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review Patients with treatment-resistant depression and bipolar depression meeting DSM-IV-TR... 2017 Retrospective observational study n = 27

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