High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression.
Stephen A Murata, Zachary B Madaj, Colt D Capan, Ryan D Sheldon, Rif S El-Mallakh, Sagar V Parikh, William V Bobo, Fernando S Goes, Owen M Wolkowitz, Jennifer L. Vande Voort, Louis J Nykamp, Balwinder Singh, Gustavo C Medeiros, Erik B Nelson, Michael E. Thase, Gregory F Oxenkrug, Mark A Frye, John F Greden, Eric D Achtyes, Lena C Brundin
Biological Psychiatry Global Open Science July 1, 2025 DOI: 10.1016/j.bpsgos.2025.100503 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Peer reviewed |
|---|---|
| Sample size | 74 |
| Population | Patients with treatment-resistant depression |
| Intervention | Intravenous racemic ketamine |
| Duration | 3 infusions over 11 days, with a subset continuing weekly infusions |
| Topics | Depression Ketamine Esketamine |
| Keywords | Biomarkers Anthranilic acid Bio-k Kynurenine pathway Predictive biomarker Depression treatment Ketamine therapy Psychiatric medicine Mental health research |
| Citations | 1 |
| Key findings | Higher baseline anthranilic acid levels and AA-based biomarker ratios predicted ketamine-induced remission in treatment-resistant depression. |
Abstract
Treatment-resistant depression (TRD) remains a challenge, but intravenous racemic ketamine offers rapid antidepressant effects. Reliable biomarkers are needed. In this study, we examined kynurenine pathway metabolites and inflammatory cytokines as predictors of ketamine response. The Bio-K study was a multicenter, open-label trial of 74 patients with TRD who received 3 ketamine infusions over 11 days. Remission (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≤9) was assessed 24 hours post infusion 3, with a subset of study participants continuing weekly infusions. Plasma biomarkers (9 kynurenines, 14 cytokines) were measured at baseline and post infusion. Mixed-effects models and logistic regression analyses were used, adjusting for sex, age, body mass index, benzodiazepine use, and baseline MADRS scores. Second-generation p values were used to determine significance. Of the 74 participants, 52% (n = 38) achieved remission. Higher baseline anthranilic acid (AA) levels predicted remission (β = -0.93, p = .02). Composite ratios, including AA:intercellular adhesion molecule-1 (ICAM-1) (β = -1.15, p = .002) and AA:tryptophan (TRP) (β = -0.98, p = .007), significantly improved predictive accuracy (area under the receiver operating characteristic curve = 0.75 vs. 0.64, p = .03). The findings were independent of demographic and clinical covariates. Elevated AA levels and AA-based biomarker ratios predicted ketamine remission in patients with TRD, supporting biomarker-driven personalized treatment. These findings highlight immunometabolic mechanisms in ketamine response.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |