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

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.