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Recent Advances in Drug Discovery and Evaluation for the Treatment...
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Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 16958

Special Issue Editors

Dr. Jolanta Orzelska-Górka

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Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Kruk-Słomka

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Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; cannabinoids
Special Issues, Collections and Topics in MDPI journals
Dr. Ewa Kędzierska

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Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Ewa Gibuła-Tarłowska

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Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Mental disorders are a major public health concern and a leading contributor to the global disease burden. There are many limitations of ongoing pharmacotherapy, especially in severe mental disorders such as affective disorders (depression, bipolar disorder, and anxiety disorders) and schizophrenia. The complex pathomechanisms of these mental disorders imply that medication responses vary across patients. The importance of the problem of mental illnesses is also emphasized by the fact of their co-occurrence, which significantly hinders proper treatment. This is why it is so important to know the pathomechanisms associated with these diseases. Depression and schizophrenia represent some of the most prevalent and highly comorbid psychiatric conditions; thus, increased effective therapeutic attention to both symptoms—mood and psychosis—is needed to improve outcomes and support prevention. Currently, the use of antipsychotic drugs, as monotherapy or as adjuncts to antidepressants and mood-stabilizing medicines, is also common practice for mood disorders that are not necessarily associated with psychosis. Furthermore, the use of many antipsychotic drugs carries a risk of serious adverse effects that may not only significantly affect a patient's quality of life but also shorten its duration. These problems are indications of the need to search for new treatments for mental diseases that are characterized by beneficial pharmacological effects and suitable safety profile actions.

Thus, this Special Issue aims to address the pressing need for the development of new drugs to treat affective disorders and/or schizophrenia. The aim of this project is to bring together international experts to provide a comprehensive overview of this research field. Therefore, I invite you to participate with either an original article or a review focused on some aspects of the subject.

Dr. Jolanta Orzelska-Górka
Dr. Marta Kruk-Słomka
Dr. Ewa Kędzierska
Dr. Ewa Gibuła-Tarłowska
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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
  • bipolar disorders
  • schizophrenia
  • mental disorders

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Published Papers (7 papers)

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Research

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17 pages, 2310 KiB  
Article
A Multi-Center, Open-Label, Single-Arm Study to Investigate the Early Effectiveness of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Using a Mobile Self-Monitoring Application
by Junhyung Kim, Seung-Hoon Lee, Cheolmin Shin, Kyu-Man Han, Sung Joon Cho, Narei Hong and Changsu Han
Pharmaceuticals 2024, 17(9), 1143; https://doi.org/10.3390/ph17091143 - 30 Aug 2024
Viewed by 847
Abstract
This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm [...] Read more.
This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18–65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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15 pages, 2507 KiB  
Article
Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression
by Veronika Kovacova, Andrea Macejova, Ingrid Tonhajzerova, Zuzana Visnovcova, Nikola Ferencova, Zuzana Mlyncekova, Tomas Kukucka, Ivan Farsky, Slavomir Nosal and Igor Ondrejka
Pharmaceuticals 2024, 17(3), 358; https://doi.org/10.3390/ph17030358 - 10 Mar 2024
Viewed by 1418
Abstract
Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal [...] Read more.
Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1–10, total score), and CDI (items A–E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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14 pages, 1823 KiB  
Article
Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study
by Jia-Ru Li, Ling-Ling Yeh, Ji-Yu Lin and Yi-Ju Pan
Pharmaceuticals 2024, 17(1), 78; https://doi.org/10.3390/ph17010078 - 8 Jan 2024
Cited by 2 | Viewed by 1283
Abstract
As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative [...] Read more.
As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the ‘no exposure’ category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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15 pages, 323 KiB  
Article
Biopsychosocial Variables in Male Schizophrenic Patients: A Comprehensive Comparison with Healthy Controls
by Krzysztof Krysta, Beata Trędzbor, Ewa Martyniak, Aleksandra Cieślik, Agnieszka Koźmin-Burzyńska, Katarzyna Piekarska-Bugiel, Katarzyna Skałacka, Rafał Bieś and Marek Krzystanek
Pharmaceuticals 2023, 16(12), 1633; https://doi.org/10.3390/ph16121633 - 21 Nov 2023
Viewed by 1746
Abstract
Objective: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). Methods: participants underwent a battery of neuropsychological tests including the Trail [...] Read more.
Objective: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). Methods: participants underwent a battery of neuropsychological tests including the Trail Making Test (TMT), Stroop Color-Word Interference Test, and Verbal Fluency Test. Psychopathological symptoms in the SZ group were evaluated using the Positive and Negative Syndrome Scale (PANSS). Anthropometric measurements such as body weight, height, BMI, and waist circumference were taken. Biochemical markers measured included fasting glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and fasting insulin. Lifestyle factors were assessed through a questionnaire for the study of views and eating habits of people aged 16 to 65. Results: the HC group outperformed the SZ group in the TMT_A test and the Stroop test, but no significant differences were observed in the TMT_B test or in phonemic fluency tests. No correlation was found between age and PANSS scores within the SZ group. Anthropometrically, the SZ group had higher body weight, waist circumference, and BMI, with no difference in height. Biochemically, the HC group had higher HDL cholesterol levels but lower insulin and insulin resistance indices. Pharmacological assessment showed a more significant impact on body weight among SZ patients taking second-generation antipsychotics. Lifestyle factors such as diet and screen time were comparable between groups, but the SZ group reported longer sleep duration and lower leisure time activity. Conclusions: our study highlights distinct neuropsychological, pharmacological, anthropometric, and biochemical differences between male schizophrenic patients and healthy controls. The results underscore the complexity of schizophrenia and point toward the need for a multi-faceted approach to its management and understanding. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)

Review

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11 pages, 1764 KiB  
Review
Involvement of the Expression of G Protein-Coupled Receptors in Schizophrenia
by Raluka Kalinovic, Andrei Pascariu, Gabriela Vlad, Diana Nitusca, Andreea Sălcudean, Ioan Ovidiu Sirbu, Catalin Marian and Virgil Radu Enatescu
Pharmaceuticals 2024, 17(1), 85; https://doi.org/10.3390/ph17010085 - 9 Jan 2024
Cited by 4 | Viewed by 1793
Abstract
The expression of GPCRs has been associated with schizophrenia, and their expression may induce morphological changes in brain regions responsible for schizophrenia and disease-specific behavioral changes. The articles included in this review were selected using keywords and databases of scientific research websites. The [...] Read more.
The expression of GPCRs has been associated with schizophrenia, and their expression may induce morphological changes in brain regions responsible for schizophrenia and disease-specific behavioral changes. The articles included in this review were selected using keywords and databases of scientific research websites. The expressions of GPRs have different involvements in schizophrenia, some increase the risk while others provide protection, and they may also be potential targets for new treatments. Proper evaluation of these factors is essential to have a better therapeutic response with a lower rate of chronicity and thus improve the long-term prognosis. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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23 pages, 1322 KiB  
Review
Research in the Field of Drug Design and Development
by Grazyna Biala, Ewa Kedzierska, Marta Kruk-Slomka, Jolanta Orzelska-Gorka, Sara Hmaidan, Aleksandra Skrok, Jakub Kaminski, Eva Havrankova, Dominika Nadaska and Ivan Malik
Pharmaceuticals 2023, 16(9), 1283; https://doi.org/10.3390/ph16091283 - 11 Sep 2023
Cited by 17 | Viewed by 6260
Abstract
The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and [...] Read more.
The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and well-tolerated compounds, as well as the ineffectiveness of existing therapies, and society’s insufficient knowledge concerning the prophylactics and pharmacotherapy of the most common diseases today, comprise a serious challenge. This can influence not only the quality of human life, but also the health of whole societies, which became evident during the COVID-19 pandemic. In general, the process of drug development consists of three main stages: drug discovery, preclinical development using cell-based and animal models/tests, clinical trials on humans and, finally, forward moving toward the step of obtaining regulatory approval, in order to market the potential drug. In this review, we will attempt to outline the first three most important consecutive phases in drug design and development, based on the experience of three cooperating and complementary academic centers of the Visegrád group; i.e., Medical University of Lublin, Poland, Masaryk University of Brno, Czech Republic, and Comenius University Bratislava, Slovak Republic. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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Other

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17 pages, 663 KiB  
Systematic Review
The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis—The Case of the Xanomeline–Trospium Combination: A Systematic Review
by Octavian Vasiliu, Beatrice Budeanu and Mihai-Ștefan Cătănescu
Pharmaceuticals 2024, 17(5), 610; https://doi.org/10.3390/ph17050610 - 9 May 2024
Cited by 2 | Viewed by 2551
Abstract
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline–trospium (KarXT) is a [...] Read more.
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline–trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline–trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs. Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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