Effects of Repeated Ketamine Infusions on Suicidal Ideation in Treatment-Resistant Depression and Associated Changes in Selected Plasma Biomarkers.
Abstract
<h4>Introduction</h4>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.<h4>Methods</h4>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 <i>p</i>-values adjusted for multiple comparisons using the false discovery rate procedure.<h4>Results</h4>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, <i>p</i>=0.01) and Quick Inventory of Depressive Symptomatology-Self Report item 12 (1.3±0.9 to 0.8±0.9, <i>p</i>=0.01). Columbia Suicide Severity Rating Scale scores numerically decreased (1.1±1.3 to 0.8±1.2, <i>p</i>=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 (<i>r</i>=- 0.40, <i>p</i>=0.03) and kynurenic acid (<i>ρ</i>=- 0.37, <i>p</i>=0.04), although these did not survive false discovery rate correction.<h4>Discussion</h4>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.
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