High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression

Background

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.

Methods

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.

Results

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.

Conclusions

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.