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Esketamine and Quality of Life Improvement in Treatment-Resistant Depression Patients: A Real-World Clinical Study.

Matteo Lupi, Alessandro Carano, Tiziano Acciavatti, Stefano Marini, Marco Palmucci, Elicio Marinucci, Enrico Paolini, Alessandro Gentile, Angelomarco Barioglio, Marco Giri, Domenico de Berardis, Giovanni Martinotti

Journal of Clinical Psychopharmacology November 21, 2025 DOI: 10.1097/jcp.0000000000002042 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational prospective multicenter study Peer reviewed
Sample size 18
Population Adults with treatment-resistant depression
Interventions Esketamine nasal spray oral antidepressant
Duration 6 months, with assessments at baseline, 1, 3, and 6 months
Measures Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), Personal and Social Performance Scale (PSP), Montgomery-Asberg Depression Rating Scale (MADRS)
Topics Esketamine Ketamine Depression
Keywords Humans Antidepressive agents Follow-up studies Prospective studies Quality of life Adult Middle aged Female Depressive disorder, treatment-resistant Real-world Treatment-resistent depression
Key findings In 18 adults with treatment-resistant depression, esketamine nasal spray plus an oral antidepressant was associated with progressive improvement in depressive symptoms (MADRS 39.2 at baseline to 15.9 at six months) and significant gains in quality of life and functioning on the Q-LES-Q-SF, SDS, and PSP. The authors conclude esketamine may offer meaningful benefit for patients with substantial quality-of-life limitations.

Abstract

Purpose: Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on subjective quality of life (QoL) and general status of adults with TRD.

Methods: The study was an observational, prospective and multicenter study comprising a total of 18 TRD patients treated with Esketamine-Nasal Spray ESK-NS. Anamnestic data and psychometric assessments were collected at baseline (T0) and at follow-ups at 1 month (T1), 3 months (T2), and 6 months (T3).

Results: Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), and Personal and Social Performance Scale (PSP) showed a statistically significant amelioration in QoL and functioning for all 3 scales, with progressive improvements at 1, 3, and 6 months. Montgomery-Asberg Depression Rating Scale (MADRS) scores decreased from a baseline score of 39.2 to 28.7 on T1, 20.9 on T2, and 15.9 on T3, respectively. Correlation analyses showed statistical significance between changes at 6 months between MADRS and QLES and between MADRS and SDS, but not between MADRS and PSP.

Conclusions: Significant improvement in QoL was observed among patients with TRD treated with ESK-NS; ESK-NS in combination with an oral AD appears to offer meaningful benefit as a treatment option for patients with TRD who generally have substantial QoL and functioning limitations as a result of their depressive illness.

Comparable studies

Other observational and cohort studies on esketamine for depression, most cited first.

Study Year Design Participants
Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression Patients with treatment-resistant bipolar depression (B-TRD) and unipolar... 2023 Observational cohort n = 70
Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. Adults with treatment-resistant depression 2023 Observational study n = 62
Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) Treatment-resistant depression patients 2023 Retrospective, multicentric, real-world study n = 149
Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study Patients with treatment-resistant depression and a substance use disorder 2023 Observational, retrospective, multicentre study n = 26
Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review Patients with treatment-resistant depression and bipolar depression meeting DSM-IV-TR... 2017 Retrospective observational study n = 27

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