Abstract / Summary
Introduction: 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.
Methods: 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.
Results: 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.
Discussion: 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.