Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response.

Background: Intranasal esketamine has recently emerged as an innovative treatment option for treatment-resistant depression (TRD). This retrospective, uncontrolled study aimed to evaluate the real-world effectiveness of esketamine in an naturalistic inpatient setting and explore demographic and clinical factors associated with treatment response.

Methods: We conducted a chart review of 101 inpatients with TRD treated with intranasal esketamine at the University Hospital Münster, Germany. Depression severity was assessed pretreatment and posttreatment with the Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck’s Depression Inventory-II (BDI-II). Repeated measures ANOVAs and logistic regression models were applied to identify treatment outcomes and associated factors.

Results: Patients (mean age 47.7 years; 51.5% women) presented with severe depression and frequent psychiatric comorbidities. Esketamine treatment led to significant improvements in MADRS (mean reduction − 10.7, p < 0.001) and BDI-II scores (mean reduction − 11.5, p < 0.001), with large effect sizes. Suicidality scores decreased significantly as well. Overall, 28.8% achieved response, 52.5% at least partial response, and 19.3% remission. Older age was associated with higher remission likelihood (OR 4.06, p = 0.041), while male gender was associated with partial response (OR 3.71, p = 0.012). Extended induction beyond eight sessions was particularly beneficial for older patients and those with psychiatric comorbidities. No treatment-related serious adverse events were observed.

Conclusions: In this large real-world inpatient cohort, intranasal esketamine significantly improved depression severity. Older patients and those with comorbid psychiatric disorders may particularly benefit from extended induction treatment. These findings support intranasal esketamine as an effective therapeutic option in TRD while highlighting the need for further controlled studies to refine patient selection and optimize treatment protocols. CLINICAL TRIAL NUMBER: Not applicable.