Symptom trajectories and clinical outcomes of intravenous ketamine in treatment-resistant depression: A real-world study using group-based trajectory modeling.

In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.

Study at a glance

Abstract

Intravenous (IV) ketamine is an emerging intervention for treatment-resistant depression (TRD), yet the temporal dynamics of response and the optimal number of infusions remain unclear, particularly in real-world clinical populations with psychiatric comorbidities. We conducted a retrospective chart review of 209 adults with TRD treated with IV ketamine at an interventional psychiatry program. Patients received four or six infusions over 2-3 weeks. Depressive and anxiety symptoms were assessed at baseline and before each infusion using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Generalized Anxiety Disorder-7 (GAD-7). One-week and one-month post-treatment assessments were available only for the four-infusion cohort due to procedural changes during early program implementation. Longitudinal symptom change was examined using linear mixed-effects models, and latent symptom-response patterns were identified through group-based trajectory modeling. Treatment response was defined as ≥50% symptom reduction, and remission as MADRS ≤10 or GAD-7 ≤ 4. Significant reductions in MADRS and GAD-7 scores were observed across treatment (p < 0.001). End-of-treatment response and remission rates were numerically higher in the six-infusion group than in the four-infusion group, though these differences were not statistically significant. Four distinct trajectory classes emerged for both depressive and anxiety symptoms, with anxiety improving more slowly and less robustly. Durability comparisons between infusion protocols could not be made because follow-up data were collected only in the four-infusion group; durability after six infusions remains unknown. IV ketamine produced statistically significant but modest symptom improvement, with substantial heterogeneity in treatment trajectories, underscoring the need for individualized, measurement-based care in real-world TRD populations.