High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression.
Biological psychiatry global open science – July 01, 2025
Source: PubMed
Summary
A blood compound called anthranilic acid may predict who will benefit most from ketamine therapy for severe depression. Higher levels of this naturally occurring substance were linked to better treatment outcomes in patients receiving ketamine infusions. This discovery could help doctors identify which patients with treatment-resistant depression are most likely to achieve remission through ketamine treatment.
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.