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. 2025 Apr 21;15(4):161.
doi: 10.3390/jpm15040161.

Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience)

Marco Di Nicola  1   2 , Maria Pepe  1   2 , Giacomo d'Andrea  3 , Ilaria Marcelli  1 , Mauro Pettorruso  3 , Ileana Andriola  4 , Stefano Barlati  5   6 , Matteo Carminati  7 , Carlo Ignazio Cattaneo  8 , Massimo Clerici  9   10 , Domenico De Berardis  11 , Sergio De Filippis  12 , Bernardo Dell'Osso  13 , Giorgio Di Lorenzo  14   15 , Giuseppe Maina  16 , Mirko Manchia  17   18 , Matteo Marcatili  9 , Vassilis Martiadis  19 , Cinzia Niolu  14 , Antonino Petralia  20 , Gianluca Rosso  16 , Gianluca Serafini  21   22 , Maria Salvina Signorelli  20 , Tommaso Vannucchi  23 , Matteo Vismara  13 , Raffaella Zanardi  7   24 , Antonio Vita  5   6 , Gabriele Sani  1   2 , Giovanni Martinotti  3 ; Real-ESKperience Study Group
Collaborators, Affiliations

Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience)

Marco Di Nicola et al. J Pers Med. .

Abstract

Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients' perspective on this treatment are limited. This multicentric Italian study explored experiences with ESK-NS in TRD patients, focusing on perceived therapeutic effects and overall satisfaction. Methods. A self-report survey was administered to 236 outpatients with TRD (55.1% females, 54.1 ± 14.1 years) treated with ESK-NS for at least three consecutive months within standard clinical care. Based on satisfaction levels, participants were classified as "unsatisfied" (10.2%), "partially satisfied" (19.1%), "satisfied" (44.4%), or "very satisfied" (26.3%), and compared for sociodemographic, clinical characteristics, and feedback on perceived benefits. Artificial intelligence (OpenAI) served to categorize responses to an open-ended question. Results. Enhanced quality of life was reported by 88.4% of participants. Significant differences emerged in earliest self-perceived benefits, most relevant effects, and impact on global functioning across groups. Specifically, "very satisfied" patients described the following: early improvements in depressed mood, suicidal thoughts, and restlessness; decreased suicidal thoughts among the most significant effects; and functional gains across all domains. OpenAI identified experiences of personal growth and rediscovery and a desire for tailored settings and approaches as recurring topics. Conclusions. Most patients reported a positive perception of ESK-NS treatment. The most satisfied participants highlighted significant benefits to depressed mood, suicidal thoughts, and overall functioning. Patient-reported experiences offer insights into different psychopathological dimensions, including functional outcomes and quality of life. Integrating these perspectives into clinical practice might assist treatment personalization, improving patients' adherence and satisfaction.

Keywords: artificial intelligence; glutamatergic system; mood disorders; patient perspective; personalized medicine; psychopharmacology.

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Conflict of interest statement

M. Di Nicola is/has been a consultant and/or a speaker and/or has received research grants from: Angelini, Janssen, Lundbeck, Neuraxpharm, Otsuka and Idorsia Pharmaceuticals. I. Andriola received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Janssen, Neuraxpharm, and Otsuka. S. Barlati received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Janssen, Lundbeck, Otsuka, and Rovi. D. De Berardis is/has been a consultant and/or a speaker for Angelini, Janssen, Lundbeck, Neuraxpharm, Otsuka, Italfarmaco, Recordati, Pfizerm and Rovi. S. De Filippis has been a consultant and/or a speaker and/or has received research grants from: Angelini, Janssen, Lundbeck, Neuraxpharm, Otsuka, Viatris, Rovi, and Molteni. G. Di Lorenzo has been a speaker and/or a consultant for Angelini, FB-Health, Janssen, Livanova, Lundbeck, Neuraxpharm, Otsuka, and Recordati. G. Maina is/has been a consultant and/or a speaker and/or has received research grants from: Angelini, Boheringer, Janssen, Lundbeck, Otsuka, Rovi, and Teva. M. Manchia is/has been a consultant and/or a speaker and/or has received research grants from: Angelini, Janssen, Lundbeck, Neuraxpharm, Rovi, Fidia, and Viatris. A. Vita received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Innova Pharma-Recordati, Janssen, Lundbeck, Otsuka, Pfizer, and Rovi. G. Sani is/has been a consultant and/or a speaker and/or has received research grants from: Angelini, Janssen, Lundbeck, Neuraxpharm, and Otsuka. G. Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen, Lundbeck, Neuraxpharm, Otsuka, Pfizer, Rovi, Servier, and Recordati. All the other authors declare that the research was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Heatmap of pairwise comparisons between subgroups for the variables of interest. * First perceived beneficial effects; # most significant beneficial effects; § areas of functioning. Shades of gray indicate the magnitude of differences between groups, with darker tones representing greater differences and higher statistics. Numeric values represent statistics from Chi-square/Fisher’s exact tests, with * p < 0.05, ** p < 0,01, *** p < 0.001 after Bonferroni correction.
Figure 2
Figure 2
Recurring topics extracted from responses to the open-ended question and categorized through OpenAI.
See this image and copyright information in PMC

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