In brief
- Four intravenous ketamine infusions (0.5 mg/kg) over two weeks were associated with a modest decrease in suicidal ideation in treatment-resistant depression.
- Two of the three scales showed a significant change; the third decreased in numerical value but failed to reach statistical significance.
- Plasma biomarkers, including kynurenic acid, remained only as leads: they did not withstand correction for multiple comparisons.
A group of Japanese researchers has published a secondary analysis of an open-label trial involving ketamine for people with treatment-resistant depression. Their question was not only whether suicidal ideation decreases, but whether any blood marker accompanies that change.
What was measured and how
Participants were outpatients with treatment-resistant depression. They received four intravenous ketamine infusions at 0.5 mg/kg over two weeks. Before and after the series, suicidal ideation was assessed using three instruments: item 10 of the Montgomery-Åsberg Depression Rating Scale, item 12 of the self-reported QIDS-SR questionnaire, and the Columbia-Suicide Severity Rating Scale (C-SSRS).
Additionally, the team quantified eleven plasma biomarkers using liquid chromatography-mass spectrometry. They then looked for correlations between changes in those molecules and changes in suicidal ideation scores, applying a statistical adjustment (false discovery rate) to avoid mistaking chance for a signal.
What the results showed
On item 10 of the Montgomery-Åsberg scale, the mean score went from 1.5 to 1.0 (p=0.01). On item 12 of the QIDS-SR, it dropped from 1.3 to 0.8 (p=0.01). On the C-SSRS, the decrease was from 1.1 to 0.8, but with p=0.17—that is, without statistical significance. The authors themselves describe these as “modest” reductions, and the figures confirm it: these are half-point movements on short scales.
Regarding the markers, unadjusted analyses showed nominal associations between improvement in the C-SSRS and increases in citric acid (r=-0.40, p=0.03) and kynurenic acid (rho=-0.37, p=0.04). After applying the correction for multiple comparisons, none remained. The authors describe them as hypotheses that require validation in larger trials.
What it implies
It is best to read this work for what it is: a secondary analysis of an open-label trial without a control group, meaning it does not allow for the separation of the drug’s effect from that of expectations, clinical support, or the natural evolution of the condition. The published summary does not detail the number of participants, so we cannot assess the study’s power. It also says nothing about the duration of the effect beyond the post-series evaluation.
Even so, it contributes to the debate on ketamine and dissociatives: the fact that kynurenic acid and citric acid appear as candidates, even if only nominally, justifies designing larger studies that measure them from the outset. A reliable biomarker, if confirmed, would help us understand why some people respond and others do not.
For those interested in the subject from a practical standpoint, the study serves as a simple reminder: the changes in suicidal ideation were small and, without a control group, cannot be confidently attributed to ketamine; they also depend on scales that each person relates to differently. For general information, the harm reduction and responsible use section contains the reference material for this site.
Source
- Murao M, Setoyama D, Matsumoto Y, Kato TA, Tachimori H, Tada T, Seki H, Tsuboi T, Watanabe K, Sakurai H. Pharmacopsychiatry. Effects of Repeated Ketamine Infusions on Suicidal Ideation in Treatment-Resistant Depression and Associated Changes in Selected Plasma Biomarkers. Published in PubMed, October 2, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
