Effects of Repeated Ketamine Infusions on Suicidal Ideation in Treatment-Resistant Depression and Associated Changes in Selected Plasma Biomarkers

This study investigated the antisuicidal effects of repeated intravenous ketamine in patients with treatment-resistant depression and explored associations between suicidal ideation and temporal changes in selected plasma biomarkers to identify potential biomarkers. This secondary analysis of an open-label trial included outpatients with treatment-resistant depression who received four intravenous ketamine infusions (0.5 mg/kg) over 2 weeks. Suicidal ideation was assessed at baseline and post-intervention using the Montgomery–Åsberg Depression Rating Scale (item 10), Quick Inventory of Depressive Symptomatology–Self Report (item 12), and Columbia Suicide Severity Rating Scale. Eleven targeted plasma biomarkers were quantified via liquid chromatography–mass spectrometry. Associations between suicidal ideation scores and biomarker changes were evaluated using Pearson’s and Spearman’s correlation coefficients, with p-values adjusted for multiple comparisons using the false discovery rate procedure. Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery–Åsberg Depression Rating Scale item 10 (1.5±1.5 to 1.0±1.3, p=0.01) and Quick Inventory of Depressive Symptomatology–Self Report item 12 (1.3±0.9 to 0.8±0.9, p=0.01). Columbia Suicide Severity Rating Scale scores numerically decreased (1.1±1.3 to 0.8±1.2, p=0.17) without reaching statistical significance. In unadjusted analyses, improved Columbia Suicide Severity Rating Scale scores showed nominal associations with increased levels of citric acid (r=− 0.40, p=0.03) and kynurenic acid (ρ=− 0.37, p=0.04), although these did not survive false discovery rate correction. Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery–Åsberg Depression Rating Scale and Quick Inventory of Depressive Symptomatology–Self Report. While no definitive biomarkers were identified after false discovery rate correction, these nominal associations are purely hypothesis-generating and require larger validation trials.