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

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 21119

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Dr. Lucie Bartova

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Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
Interests: psychopharmacotherapy; antidepressant agents; affective disorders; depression; anxiety; major depressive disorder; treatment-resistant depression; long COVID; ME/CFS (myalgic mncephalomyelitis/chronic fatigue syndrome)
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Special Issue Information

Dear Colleagues,

We are very delighted to cordially invite you to contribute to our upcoming Special Issue titled “Innovations in the Treatment for Depression and Anxiety”, which seeks to address some of the most exciting and pressing challenges in the management of these widespread mental health conditions.

Depression and anxiety continue to impose significant burdens on individuals and families, as well as healthcare and socioeconomic systems worldwide. Despite advances in understanding their underlying mechanisms, clinical manifestations, and treatments, insufficient symptom relief and the need for more personalized and accessible care remain critical issues. This Special Issue aims to explore novel approaches and interdisciplinary strategies that hold promise for overcoming these barriers.

We welcome submissions covering a broad range of topics, including advancements in pharmacological treatments, neuromodulation techniques, digital and telehealth interventions, psychotherapeutic innovations, and integrated care models. Studies investigating biomarkers, neurobiological underpinnings, and precision medicine approaches are also highly encouraged. Research focusing on underserved populations, comorbidities, and scalable treatment options will provide valuable insights for real-world applications.

This Special Issue aims to foster collaboration among researchers and clinicians, driving the translation of emerging findings into practical treatments that will improve patient outcomes.

We encourage you to submit original research articles and reviews that contribute to this critical and dynamic field.

We look forward to your valuable contributions and the opportunity to advance the future of mental healthcare together.

With my very best wishes, many thanks and kindest regards from Vienna.

Dr. Lucie Bartova
Guest Editor

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

depression
anxiety
antidepressant
anxiolytic
psychopharmacotherapy
psychotherapy
brain stimulation
treatment
response
resistance

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Related Special Issue

Innovations in the Treatment for Depression and Anxiety—2nd Edition in Journal of Clinical Medicine

Published Papers (8 papers)

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Research

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23 pages, 953 KB

Open AccessArticle

Comparative Efficacy of Brief Psychoanalytic Psychotherapy and Cognitive Behavioral Therapy for Generalized Anxiety Disorder: A Randomized Controlled Trial

by Metin Çınaroğlu, Eda Yılmazer, Selami Varol Ülker and Gökben Hızlı Sayar

J. Clin. Med. 2026, 15(4), 1472; https://doi.org/10.3390/jcm15041472 - 13 Feb 2026

Viewed by 1320

Abstract

Background: Cognitive behavioral therapy (CBT) is the most established psychological treatment for generalized anxiety disorder (GAD), yet many patients do not achieve full remission. Brief psychoanalytic psychotherapy represents a theoretically distinct alternative, but direct controlled comparisons remain limited. This study examined the short-term efficacy of brief psychoanalytic psychotherapy and CBT relative to a waitlist control in adults with GAD. Methods: In a three-arm randomized controlled trial, 60 adults with DSM-5-diagnosed GAD were allocated to brief psychoanalytic psychotherapy (12 weekly sessions), CBT (12 weekly sessions), or a waitlist control. Assessments were conducted at pre-treatment and post-treatment. The primary outcome was anxiety severity measured by the Beck Anxiety Inventory (BAI). Secondary outcomes included depressive symptoms (BDI-II), quality of life (WHOQOL-BREF), functional impairment (WHODAS 2.0), and therapeutic alliance (Working Alliance Inventory). Data were analyzed using mixed-design ANOVAs and effect size estimates. Results: Both active treatments produced significantly greater reductions in anxiety than the waitlist control, with large effect sizes. Mean BAI scores decreased by 14.5 points in the psychoanalytic group and 16.3 points in the CBT group, compared to minimal change in the waitlist condition. Similar patterns were observed for depressive symptoms, quality of life, and functional impairment, with both therapies outperforming waitlist controls on all secondary outcomes. No statistically significant differences were found between CBT and brief psychoanalytic psychotherapy on any outcome measure. Therapeutic alliance ratings were high and comparable across the two active treatments. Conclusions: Brief psychoanalytic psychotherapy and CBT were both effective short-term treatments for GAD and superior to no treatment, with no significant differences between the two modalities at post-treatment. These findings suggest that time-limited psychoanalytic psychotherapy may represent a promising short-term therapeutic option to CBT for GAD, expanding treatment options for patients and clinicians. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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27 pages, 1017 KB

Open AccessArticle

Use and Perceived Helpfulness of Different Intervention Strategies in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Depression

by Marie Celine Dorczok, Nilufar Mossaheb, Gloria Mittmann, Marina F. Thomas, Lucie Bartova, Beate Schrank and Verena Steiner-Hofbauer

J. Clin. Med. 2026, 15(2), 849; https://doi.org/10.3390/jcm15020849 - 20 Jan 2026

Viewed by 1319

Abstract

Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or depression both frequently report debilitating exhaustion, yet the two conditions differ in their etiological and diagnostic clarity, and clinical management. This study aimed to examine differences in the use and perceived helpfulness of a broad range of conventional treatments and complementary interventions, including nutritional approaches, between patients with ME/CFS and depression. Methods: A cross-sectional online survey was conducted in 2024. A total of 819 participants self-identified as having either ME/CFS (n = 576) or depression (n = 243). Participants (80% female) reported their use and perceived helpfulness of 52 treatments and interventions, encompassing behavioral therapies, medications, and dietary supplements. Group differences were examined using multivariate analyses of variance and covariance (MANOVA/MANCOVA). Open-ended responses were analyzed descriptively using thematic grouping and frequency counts. Results: Participants with depression most commonly reported the use of psychotherapy (M = 2.49, SD = 1.00) and antidepressant medication (M = 2.44, SD = 2.30), and they rated fewer interventions as helpful compared to participants with ME/CFS. In contrast, participants with ME/CFS reported a significantly broader engagement with diverse intervention modalities, particularly pacing (M = 2.73, SD = 0.80) and dietary supplements (M = 2.43, SD = 1.09), and perceived many of them as helpful. Group differences remained significant after controlling for age, gender, and whether treatment was medically recommended. Supplements targeting energy metabolism (e.g., CoQ10, NADH) were especially favored among ME/CFS participants. Conclusions: Findings suggest that participants with ME/CFS tend to adopt an exploratory and expansive intervention approach, potentially reflecting the lack of standardized guidelines and limited effectiveness of available treatment options. Participants with depression, in contrast, appeared to follow more guideline-concordant, evidence-based treatment pathways. Taken together, the findings point to a need for further development and evaluation of empirically supported, patient-centered treatment and intervention strategies for ME/CFS and suggest differences in clinical care structures between ME/CFS and depression. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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13 pages, 1196 KB

Open AccessArticle

Socially Assistive Robot Hyodol for Depressive Symptoms of Community-Dwelling Older Adults in Medically Underserved Areas: A Preliminary Study

by Han Wool Jung, Yujin Kim, Hyojung Kim, Min-kyeong Kim, Hyejung Lee, Jin Young Park, Woo Jung Kim and Jaesub Park

J. Clin. Med. 2026, 15(1), 217; https://doi.org/10.3390/jcm15010217 - 27 Dec 2025

Viewed by 966

Abstract

Background/Objectives: Socially assistive robots effectively support elderly care when they incorporate personalization, person-centered principles, rich interactions, and careful role setting with psychosocial alignment. Hyodol, a socially assistive robot designed for elderly people, embodies a grandchild’s persona, emulating the grandparent–grandchild relationship. Based on the behavioral activation principles and a human-centered approach, this robot continuously supports users’ emotional well-being, health management, and daily routines. Methods: The current study evaluated Hyodol’s impact on depressive symptoms and other quality of life factors among older adults living in medically underserved areas. A total of 278 participants were assessed for depressive symptoms, loneliness, medication adherence, and user acceptance. Results: After six months of use, participants showed significant reductions in overall depressive symptoms, with a 45% decrease in the proportion of individuals at high risk of depression. Significant improvements were also observed in loneliness and medication adherence. Participants reported high levels of user acceptance and satisfaction, exceeding 70% of the total score. Participants who engaged more frequently in free chat with Hyodol showed greater improvements in depressive symptoms. Conclusions: These results highlight Hyodol’s potential as a promising tool for enhancing mental healthcare and overall well-being in this population. This at-home mental-healthcare framework can complement primary care and, if its effects are confirmed in controlled trials, could contribute to reducing healthcare burden and preventing the onset and escalation of depressive symptoms. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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10 pages, 1171 KB

Open AccessArticle

Efficacy of Adaptol^® 500 mg Tablets in Patients with Anxiety and Somatic Symptoms of Anxiety Disorder: A Noninterventional Study

by Maris Taube, Guna Dansone and Yulia Troshina

J. Clin. Med. 2025, 14(22), 7972; https://doi.org/10.3390/jcm14227972 - 10 Nov 2025

Cited by 1 | Viewed by 2910

Abstract

Background: Anxiety disorders, including panic disorder, agoraphobia, specific phobias, and generalized anxiety disorder, are among the most frequent psychiatric conditions in primary care. They often present with somatic symptoms such as dyspnea, palpitations, chest or gastrointestinal discomfort, sweating, or flushing. Adaptol^® is a non-benzodiazepine anxiolytic with nootropic properties that modulates the limbic-reticular system, hypothalamic emotional centers, and multiple neurotransmitter systems. This study aimed to assess the association between Adaptol^® use and changes in anxiety symptoms, including somatic manifestations, in routine practice. Methods: A noninterventional observational study was conducted in 100 adults diagnosed with anxiety disorders in primary care. All received Adaptol^® 500 mg as prescribed. Patients had to have mild-to-moderate anxiety (5–14 points according GAD-7) to be enrolled. Exclusion criteria ruled out individuals with concomitant psychiatric or severe somatic conditions and those with use of other medications or any interventions that could affect the symptoms. Anxiety severity and somatic symptom burden were assessed at baseline and after treatment. Results: Adaptol^® treatment was associated with reduction in anxiety and somatic complaints. Improvements were reported in palpitations, chest discomfort, gastrointestinal disturbances, and autonomic symptoms. Greater benefit was observed in male patients, though without significance testing, and in those with severe baseline anxiety, as demonstrated by correlation between GAD-7 scores at baseline and changes after the treatment (r = 0.5). No unexpected adverse events occurred. Conclusions: In this real-world study, Adaptol^® showed anxiolytic efficacy and good tolerability, improving both psychological and somatic manifestations of anxiety disorders. These findings support its use in primary care, especially in severe cases of anxiety. Controlled trials are needed to support these results. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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14 pages, 1371 KB

Open AccessArticle

Comparison of High-Charge Protocol vs. Dose Titration Protocol in Bilateral ECT: Evaluation of Antidepressant Effectiveness and EEG Parameters

by Piotr Jażdżyk, Agnieszka Kuc, Albert Stachura, Agnieszka Segiet-Święcicka, Marcin Kosmalski, Łukasz Święcicki, Eric van Exel and Tadeusz Pietras

J. Clin. Med. 2025, 14(18), 6490; https://doi.org/10.3390/jcm14186490 - 15 Sep 2025

Cited by 1 | Viewed by 1478

Abstract

Objectives: Recently, we modified the method of dosing charge in daily practice for patients undergoing bilateral electroconvulsive treatment (BL ECT). The aim of this study is to compare the effectiveness of two charges’ dosing protocols—High-Charge Protocol (HCP; based on the modified age-based method) and Dose Titration Protocol (DTP) in BL ECT for the treatment of patients with a depressive episode. Methods: The retrospective analysis compared the outcomes of BL ECT between patients receiving either HCP or DTP treatments. Patients’ mental status was assessed retrospectively using the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. EEG parameters, including seizure duration and EEG ictal activity were analyzed. Results: When compared to DTP, the HCP group was older (55 years ± SD 15 vs. 41 years ± SD 17), had lower initial CGI-S (5 [IQR 5–6] vs. 6 [IQR 5–6]) and longer disease duration (15 years [IQR 7–20] vs. 9 years [IQR 3–18]). The DTP group had a higher percentage of remission (n = 17 [77.3%]) compared to the HCP group (n = 23 [43.4%]), with the same average number of sessions performed. In addition, the DTP group had significantly longer average seizure duration (68.6 s [IQR 52.7–84.7] vs. 38.4 s [IQR 33.8–47.1], adj. p < 0.001). Conclusions: Our results suggest that in BL ECT, administering high-charge protocols may have a detrimental impact on ECT effectiveness. Based on our findings, we propose adjusting the dosing in BL ECT according to the individual seizure threshold and avoiding frequent charge increases during the course of treatment. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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Review

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13 pages, 463 KB

Open AccessReview

Patients’ Voices on Ketamine for Treatment-Resistant Depression: A Narrative Review of Qualitative Perspectives

by Michał Walaszek, Wiesław Jerzy Cubała and Zofia Kachlik

J. Clin. Med. 2026, 15(1), 150; https://doi.org/10.3390/jcm15010150 - 25 Dec 2025

Viewed by 2058

Abstract

Treatment-resistant depression (TRD) remains a significant public-health challenge, with many patients failing to respond to conventional therapies. Ketamine has emerged as a rapid-acting intervention, but quantitative outcomes alone do not capture patients’ lived experiences, which shape engagement, acceptability, and adherence. We conducted a narrative review of qualitative and mixed-methods studies to enable conceptual integration and thematic synthesis of patients’ experiences with ketamine treatment for depression, guided by established narrative review methodology and the SANRA framework. A targeted search of MEDLINE and Scopus (November 2025) identified studies reporting adult patients’ perspectives on therapeutic ketamine or esketamine use, with qualitative data synthesized iteratively in keeping with narrative review principles. Across the literature, patients’ perspectives coalesce around key thematic domains, including motivations and expectations for treatment, the phenomenology of the treatment experience, post-treatment trajectories, side effects and reasons for discontinuation, relational and environmental factors, and information and education needs. By focusing on these thematic groups, the review highlights the experiential dimensions that influence the perceived value and acceptability of ketamine, underscoring the need for patient-centered service design. Integrating these insights can guide the development of ketamine programs that are both evidence-based and aligned with patients’ priorities and perspectives. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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20 pages, 642 KB

Open AccessReview

Efficacy and Safety of Transcranial Magnetic Stimulation for Treating Late-Life Depression: A Scoping Review

by Ciprian-Ionuț Băcilă, Monica Cornea, Andrei Lomnasan, Claudia Elena Anghel, Andreea Maria Grama, Cristina Elena Dobre, Silvia Rusu and Bogdan Ioan Vintilă

J. Clin. Med. 2025, 14(10), 3609; https://doi.org/10.3390/jcm14103609 - 21 May 2025

Cited by 1 | Viewed by 8410

Abstract

Background/Objectives: Transcranial magnetic stimulation (TMS) is a non-invasive and well-tolerated treatment, offering an effective alternative for elderly patients with depression, especially when side effects or comorbidities limit medication. Methods: This scoping review analyzes 16 studies published over the past seven years, to evaluate the efficacy, safety, and clinical applications of TMS in older adults with depression. Results: The review examines various TMS modalities, including repetitive TMS (rTMS), deep TMS, and theta burst stimulation (TBS), with most protocols targeting the dorsolateral prefrontal cortex (DLPFC). Adverse effects were rare, mild, and transient, supporting the treatment’s safety profile. Pharmacological co-treatment was common but not essential for clinical improvement, highlighting TMS’s potential as a standalone therapy. A subset of studies used neuroplasticity (SICI, ICF, CSP) or neuroimaging measures (MRI and MRI-based neuronavigation), revealing that age-related cortical inhibition may limit plasticity rather than depression itself. Conclusions: Overall, TMS demonstrates promising effectiveness and tolerability in managing late-life depression. Across studies, remission rates varied from 20% to 63%, with higher efficacy generally observed in bilateral stimulation or high-frequency protocols. Standardization of protocols and further research into individualized targeting and long-term outcomes are warranted to support broader clinical adoption. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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Other

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20 pages, 2126 KB

Open AccessProtocol

Identifying Neurobehavioral Biomarkers of Anxiety and Treatment Response Using Virtual Reality, Electroencephalography, Magnetic Resonance Imaging, and Related Multimodal Assessments: A Longitudinal Study Protocol

by Hyemin Oh, Jiook Cha, Byung-Hoon Kim, Kang-Seob Oh, Young Chul Shin, Sang-Won Jeon, Sung Joon Cho and Junhyung Kim

J. Clin. Med. 2026, 15(1), 7; https://doi.org/10.3390/jcm15010007 - 19 Dec 2025

Viewed by 1220

Abstract

Background/Objectives: Anxiety disorders are highly prevalent and impairing psychiatric conditions. Conventional diagnostic approaches based on symptom checklists lack biological specificity and often fail to guide treatment decisions effectively. This study protocol outlines a multidimensional, prospective investigation designed to identify behavioral and neurobiological biomarkers predictive of treatment response in individuals with anxiety-related symptoms, grounded in the Research Domain Criteria framework. Methods: This observational, longitudinal study (NCT06773585) will include a transdiagnostic sample of clinical anxiety group alongside a healthy control group (185 participants, including 145 patients with anxiety disorders and 40 healthy controls). Participants will undergo comprehensive baseline assessments, including clinical interviews, self-report questionnaires, a virtual reality (VR)-based behavioral task, electroencephalography (EEG), electrocardiography (ECG), and structural and functional brain magnetic resonance imaging. Follow-up assessments will be conducted at 2, 6, and 12 months, with recruitment and data collection planned from 2024 to 2029. These complementary modalities are integrated to capture behavioral, physiological, and neural indicators of anxiety and its treatment response. Multimodal baseline features will be used to construct machine-learning models predicting treatment response, defined as ≥40% reduction in anxiety severity scores. Longitudinal analyses will examine symptom trajectories and neural mechanisms associated with response. Neurobiological comparisons will be made across timepoints and between responders, non-responders, and healthy controls. Conclusions: By identifying objective, biologically grounded markers of anxiety and treatment response, our findings will contribute to the development of personalized assessment tools and scalable digital interventions for psychiatric care. Full article

(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)

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