Abstract
Abstract
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.