Both intravenous (IV) racemic ketamine and intranasal (IN) esketamine have emerged as rapid-acting antidepressants for treatment-resistant depression (TRD) and are increasingly used in clinical settings. Relatively few studies, however, have compared these interventions in larger, naturalistic cohorts. This study was conducted to assess the comparative efficacy and rapidity of response observed with repeated IV ketamine versus IN esketamine in a psychiatric neurotherapeutics specialty service. Through retrospective chart review, we conducted what is, to the best of our knowledge, among the larger such comparisons to date.Data from 153 patients with severe TRD were reviewed (111 patients received IV ketamine and 42 patients received IN esketamine). In accordance with consensus criteria for TRD and validated objective criteria for illness severity, included patients failed a minimum of 2 adequate antidepressant treatment trials and demonstrated a preketamine treatment score of 16 or higher on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR). Severity of depression was subsequently reassessed with the QIDS-SRprior to each ketamine and esketamine administration. A 2-way analysis of variance was used to compare changes in QIDS-SRscores between the IV ketamine and IN esketamine treatment groups.With equivalent depression severity measured by QIDS-SRat pretreatment baseline, the IV ketamine treatment group showed significantly greater decreases in QIDS-SRscores compared to the IN esketamine group, as measured immediately before each treatment from the third to the eighth session (allvalues < .05). Patients who received IV ketamine infusions demonstrated a 49.22% reduction in QIDS-SRscores by the eighth treatment, while patients who received IN esketamine over the same induction period showed a 39.55% reduction. As expected, both IV ketamine and IN esketamine treatments resulted in significant decreases in QIDS-SRscores. In the IV ketamine group, the decrease in QIDS-SRscores reached significance after 1 treatment, while in the IN esketamine treatment group, the decrease in QIDS-SRscores reached significance after the second treatment.In this naturalistic sample of patients with similarly severe TRD treated in a ketamine subspecialty service over a 4-5-week induction period, treatment with IV racemic ketamine was associated with a more rapid response and greater overall efficacy than treatment with IN esketamine. Objective: Methods: Results: Conclusion: 16 16 16 16 16 16 16 16 16P
