Long-Term Outcomes in Patients With Treatment-Refractory Depression Receiving Intravenous Ketamine and Intranasal Esketamine: An Observational Study

Balwinder Singh, MD, MS; Vanessa K. Pazdernik, MS; Simon Kung, MD; Jennifer L. Vande Voort, MD

J Clin Psychiatry 2025;86(3):25m15831

Abstract

Objective: This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting with repeated ketamine/esketamine maintenance therapy.

Methods: This was a single-center, observational study of adults with TRD who completed acute-phase treatment between August 17, 2017, and June 24, 2021, and received IV-KET (0.5 mg/kg) or IN-ESK (56/84 mg) maintenance therapy. Maintenance cycle duration was measured from the first treatment after the acute phase to the final treatment. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology before each treatment. Linear mixed-effects models and generalized linear mixed models (GLMM) evaluated treatment effects. The number of days between treatments (treatment intervals) was modeled using a negative binomial GLMM.

Results: Fifty-six maintenance cycles from 38 patients were included. The median baseline age was 46.2 years (78.9% female). Sixty-eight percent (n = 26) received IV-KET, and 32% (n = 12) received IN-ESKET. The median duration of the longest maintenance cycle was 61 weeks for IV-KET and 48 weeks for IN-ESKET, with 14 and 28 median treatments, respectively. IV-KET patients had longer intervals between treatments compared to IN-ESKET (incidence rate ratio: 1.75, P < .001). Mean treatment intervals were 18.9 days for IV-KET vs 10.8 days for IN-ESKET. Both treatments showed stable systolic blood pressure trajectories.

Conclusion: This study provides evidence regarding longer durability of IV-KET compared to IN-ESKET. These findings need to be replicated in larger prospective studies and confirmed in a randomized controlled trial comparing these two treatment interventions.

J Clin Psychiatry 2025;86(3):25m15831

Author affiliations are listed at the end of this article.

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