Clinical characterization and real-world management of patients treated with intranasal esketamine in a tertiary treatment-resistant affective disorders unit

Background

Intranasal esketamine has emerged as a novel therapeutic option for treatment-resistant depression (TRD), particularly in patients with complex affective disorders and high clinical burden. Despite evidence from randomized controlled trials, there is still a relative paucity of real-world data from tertiary care settings, where patients often present with greater clinical complexity, psychiatric comorbidity, and more advanced stages of illness. In such contexts, clinical decision-making, patient selection, and longitudinal outcomes may differ significantly from controlled trial conditions. Understanding how esketamine is used in routine practice is therefore essential to better characterize its role in complex, treatment-resistant populations. [1-3]

Aims

To describe the clinical characteristics, treatment patterns, and observed outcomes of patients receiving intranasal esketamine in a tertiary treatment-resistant affective disorders unit under routine clinical practice conditions.

Methods

We conducted a retrospective descriptive case series including a preliminary sample of approximately ten patients, with ongoing data collection at the time of submission. Patients were treated in a specialized tertiary unit for treatment-resistant affective disorders. Data were obtained from electronic medical records and clinician-based longitudinal assessments. Variables of interest included clinical and demographic characteristics, diagnostic profile, degree of treatment resistance (defined by multiple prior treatment failures), presence of psychiatric comorbidities, and history of suicidal ideation or behavior. Treatment-related variables included treatment phase (induction vs. maintenance), dosing patterns, and concomitant pharmacotherapy. Clinical outcomes were assessed through clinician-based evaluation, focusing on global clinical impression and key depressive symptom domains (including anhedonia, energy/motivation, and suicidal ideation), as well as treatment tolerability and treatment continuation over time. Due to the naturalistic design, standardized psychometric scales were not systematically available.

Results

Patients represented a highly selected population with severe and complex affective disorders, characterized by marked treatment resistance, frequent psychiatric comorbidity, and a high prevalence of suicidal ideation. Esketamine was initiated in the context of persistent depressive symptoms despite multiple prior treatment attempts, often following inadequate response to several pharmacological strategies. Clinically meaningful improvement was observed in a subset of patients, particularly in domains such as affective reactivity, energy, and reduction of suicidal ideation. However, a notable heterogeneity in clinical response trajectories was observed, with some patients showing partial or limited benefit, suggesting variability in treatment sensitivity across individuals. Esketamine was generally well tolerated, with transient dissociative symptoms being the most commonly reported adverse effect, and no unexpected safety signals were identified.

Conclusions

In this real-world case series from a tertiary treatment-resistant affective disorders unit, intranasal esketamine was associated with clinically observable improvement in a subset of patients with complex clinical profiles, alongside an acceptable tolerability profile. The observed heterogeneity in response highlights the need for improved clinical phenotyping to optimize patient selection. Furthermore, the absence of standardized outcome measures underscores the importance of integrating structured assessments into routine clinical practice in tertiary settings.

References

1. Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, Mazzucco C, Hough D, Thase ME, Shelton RC, Molero P, Vieta E, Bajbouj M, Manji H, Drevets WC, Singh JB. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry. 2019 Jun 1;176(6):428-438. doi: 10.1176/appi.ajp.2019.19020172. Epub 2019 May 21. Erratum in: Am J Psychiatry. 2019 Aug 1;176(8):669. doi: 10.1176/appi.ajp.2019.1768correction1. PMID: 31109201.
2. Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, Lane R, Lim P, Duca AR, Hough D, Thase ME, Zajecka J, Winokur A, Divacka I, Fagiolini A, Cubala WJ, Bitter I, Blier P, Shelton RC, Molero P, Manji H, Drevets WC, Singh JB. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/jamapsychiatry.2019.1189. PMID: 31166571; PMCID: PMC6551577.
3. Vasiliu O. Esketamine for treatment‑resistant depression: A review of clinical evidence (Review). Exp Ther Med. 2023 Jan 25;25(3):111. doi: 10.3892/etm.2023.11810. PMID: 36793329; PMCID: PMC9922941.