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New Clinical Advances in Depressive Disorders and Treatment-Resistant Depression
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New Clinical Advances in Depressive Disorders and Treatment-Resistant Depression

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Mental Health".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 2170

Special Issue Editors

Dr. Giacomo d'Andrea

E-Mail Website
Guest Editor
1. Department of Neurosciences, Imaging and Clinical Sciences, Università degli Studi G. d'Annunzio, 66100 Chieti, Italy
2. Department of Mental Health, ASL 02 Lanciano-Vasto-Chieti, Italy
Interests: treatment-resistant-depression; rapid-acting antidepressant; ketamine; esketamine; non invasive brain stimulation techniques; rTMS; iTBS; machine-learning approaches; MDD; bipolar disorder; treatment-resistant bipolar depression; psylocibin
Dr. Miriam Olivola

E-Mail Website
Guest Editor
1. Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy
2. Department of Mental Health and Addiction Services, ASST Fatebenefratelli-Sacco, Milan, Italy
Interests: treatment-resistant depression; esketamine and novel antidepressants; family psychotherapy; mood disorders; psychosis

Special Issue Information

Dear Colleagues,

I am pleased to invite you to contribute to a Special Issue of the Journal of Clinical Medicine, “New Clinical Advances in Depressive Disorders and Treatment-Resistant Depression.” Major depressive disorder is not a unitary condition but a spectrum of syndromes with diverse symptom constellations, trajectories, comorbidities, and biological underpinnings. This clinical heterogeneity drives variability in outcomes and fuels the challenge of treatment resistance—demanding approaches that move beyond one-size-fits-all care.

We welcome manuscripts that transform heterogeneity into actionable precision: phenotypic refinement across the lifespan; integration of biomarkers (neuroimaging, inflammatory, and genetic), neurocognitive measures, and digital phenotyping; predictive modeling for course and treatment selection; rapid-acting and mechanism-based therapies (e.g., ketamine/esketamine), optimized neuromodulation, and psychotherapy sequencing/augmentation; as well as measurement-based care, real-world evidence, and pragmatic trials.

Original research, rigorous reviews and meta-analyses, as well as perspectives on innovative fields and protocols, are encouraged. If you are unsure about fit, feel free to contact me—I would be delighted to discuss potential submissions.

Dr. Giacomo d'Andrea
Dr. Miriam Olivola
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • treatment-resistant depression
  • MDD
  • ketamine
  • esketamine
  • rTMS
  • psylocibin
  • bipolar depression
  • clinical pheno-typing
  • precision psychiatry
  • biomarkers

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Published Papers (2 papers)

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Research

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12 pages, 1078 KB  
Article
Effectiveness of Intranasal Esketamine on Suicidal Ideation and Depressive Symptoms in Patients with Treatment-Resistant Depression: A Longitudinal Study
by Matteo Leonardi, Alice Frediani, Maria Chiara Angeletti, Monica Biseo, Giada Versaci, Michele Castiglioni, Miriam Olivola, Matteo Vismara, Alberto Varinelli, Monica Bosi, Beatrice Benatti, Natascia Brondino and Bernardo Maria Dell’osso
J. Clin. Med. 2026, 15(1), 250; https://doi.org/10.3390/jcm15010250 - 29 Dec 2025
Viewed by 1002
Abstract
Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatment-resistant depression (TRD), and the management of this condition should be as rapid and effective as possible. Intranasal Esketamine has shown promise in patients with TRD due to its rapid onset [...] Read more.
Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatment-resistant depression (TRD), and the management of this condition should be as rapid and effective as possible. Intranasal Esketamine has shown promise in patients with TRD due to its rapid onset of action on both SI and depressive symptoms. Since this medication has been recently approved, real-world data on its efficacy remain scarce, and little is known about which patients are most likely to benefit from this approach. Aims: This study aimed (1) to evaluate the efficacy of intranasal Esketamine on SI and depressive symptoms and (2) to find potential predictors of clinical response. Methods: Patients with TRD who received intranasal Esketamine were included in this study. Clinical evaluations and psychometric assessments were made at baseline (T0) and at five subsequent time points (one week [T1], one month [T2], two months [T3], three months [T4], and six months [T5]). SI was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS). Furthermore, sociodemographic, clinical, and pharmacological data were collected. Results: Eighty patients diagnosed with TRD were enrolled. Suicidal ideation (C-SSRS items 1–5) decreased from 1.56 ± 1.65 at baseline to 0.78 ± 1.28 at T1 and 0.12 ± 0.52 at T5 (all p < 0.001). MADRS fell from 31.81 ± 7.94 to 23.62 ± 9.08 and 10.19 ± 7.33 at the same time points (all p < 0.001). By T1, 68.4% achieved an SI response on the C-SSRS. The MADRS response rate increased from 16.7% at T1 to an overall response of 62.5% at T5. Male sex predicted lower odds of early response on the C-SSRS (OR = 0.21, p = 0.031); no other baseline variable was significant as a predictor. Conclusions: Intranasal Esketamine has been shown to be effective in the rapid reduction and lysis of SI in patients with TRD. Male gender was found as a negative predictor of response, suggesting the importance of considering gender differences during treatment planning. Full article
(This article belongs to the Special Issue New Clinical Advances in Depressive Disorders and Treatment-Resistant Depression)
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Review

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17 pages, 1122 KB  
Review
Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression
by Vassilis Martiadis, Fabiola Raffone, Serena Testa, Concetta Iaccarino, Paolo Giunnelli, Ada Orrico, Emilia Carbone, Salvatore Clemente, Carmine De Simone, Antonietta Massa, Clemente Purcaro, Azzurra Martini, Enrico Pessina and Carlo Ignazio Cattaneo
J. Clin. Med. 2026, 15(4), 1629; https://doi.org/10.3390/jcm15041629 - 20 Feb 2026
Cited by 1 | Viewed by 723
Abstract
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providing rapid symptom relief when conventional antidepressant strategies fail. While its pharmacological efficacy has been demonstrated in randomized controlled trials, less attention has been paid to the [...] Read more.
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providing rapid symptom relief when conventional antidepressant strategies fail. While its pharmacological efficacy has been demonstrated in randomized controlled trials, less attention has been paid to the organizational, relational, and multidisciplinary aspects that influence its real-world implementation and clinical effectiveness. While practical recommendations for intranasal esketamine services exist, an implementation-ready framework integrating psychiatry, nursing, and psychotherapy across treatment phases is still lacking. This narrative review synthesizes the clinical and real-world evidence and proposes a phase-based integration framework with explicit role delineation and measurable implementation/fidelity indicators. Methods: We conducted a narrative review informed by a structured literature search in major databases from inception to the most recent update. Search terms combined ‘esketamine’/‘Spravato’ with ‘treatment-resistant depression’, ‘nursing’, ‘psychotherapy’, ‘multidisciplinary’, and ‘implementation’. Outcomes prioritized in the synthesis included depressive symptom severity/response, relapse prevention, safety/tolerability, anhedonia, suicidality monitoring, functional outcomes, and patient-reported experience/retention. Based on this evidence, an integrated, phase-based multidisciplinary framework for esketamine treatment was developed. Results: Available evidence supports the efficacy of intranasal esketamine in reducing depressive symptoms in TRD, with growing real-world data confirming its effectiveness and safety. Beyond global symptom improvement, studies highlight benefits on clinically relevant domains such as anhedonia and suicidality trajectories, as well as meaningful patient-reported outcomes. However, the complexity of esketamine delivery requires structured clinical pathways. The proposed model delineates complementary roles for medical supervision, nursing care, and psychotherapy across pre-treatment assessment, induction and session delivery, post-session integration, and maintenance phases, emphasizing safety, continuity of care, and patient-centred monitoring. Conclusions: Intranasal esketamine represents not only a pharmacological innovation but also a treatment that necessitates an integrated multidisciplinary approach. A structured phase-based multidisciplinary approach may support safer, more acceptable delivery of intranasal esketamine and potentially improve retention and patient experience; however, prospective implementation and comparative studies are needed to evaluate clinical effectiveness, feasibility, and cost-effectiveness. Full article
(This article belongs to the Special Issue New Clinical Advances in Depressive Disorders and Treatment-Resistant Depression)
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