Current Pharmaceutical Design - Volume 27, Issue 39, 2021

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders, and in this case, they can be treated with clozapine. Based on the previous reviews on novel antipsychotic drugs, it is important to know whether the add-on therapy with the new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objectives: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of the currently available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects, and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole, and lumateperone have been updated. Published case reports of patients with treatment-resistant psychoses have also been discussed in this study. These patients were treated only with clozapine, as a result of which a high PANSS total score was observed. Only the add-on therapy with cariprazine improved the score, and above all, the negative schizophrenic symptoms and cognitive functions were improved. For the ensurance of a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs might be a choice for the maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, have been investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by the add-on therapy with cognitionenhancing drugs.

Psychoses and affective disorders are severe mental illnesses with a considerable negative effect on an individual and global scale. They are among the most damaging and socially significant diseases, which contribute to permanent disabilities for the patients. The aim of this review is to analyse the capacity of neuroscientific methods as tools to reform psychiatry into a biologically valid medical discipline. Furthermore, it will focus on the application of the translational approach towards the diagnostic and therapeutic processes, as well as monitoring of treatment response by using valid biomarkers and psychometric instruments. By combining translational neuroscience with the latest psychopharmacology advances, clinicians might be able to provide better quality of precision and individualized medical care for their patients. We visualise a reality in which neuroimaging methods will modify the standard clinical evaluation of neuropsychiatric disorders, leading to a biologically valid diagnosis, monitoring and treatment in everyday clinical practice.

Background: Diagnosis of schizophrenia lacks reliable medical diagnostic tests and robust biomarkers applied to clinical practice. Schizophrenic patients undergoing treatment with antipsychotics suffer reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose them to develop metabolic syndrome, which is also exacerbated by medication. Metabolomics is an emerging and potent technology able to accelerate this biomedical research. Aim: This review focus on a detailed vision of the molecular mechanisms involved both in schizophrenia and antipsychotic-induced metabolic syndrome, based on innovative metabolites that consistently change in nascent metabolic syndrome, drug-naïve, first episode psychosis and/or schizophrenic patients compared to healthy subjects. Main Lines: Supported by metabolomic approaches, although not exclusively, noteworthy variations are reported mainly through serum samples of patients and controls in several scenes: 1) alterations in fatty acids, inflammatory response indicators, amino acids and biogenic amines, biometals, and gut microbiota metabolites (schizophrenia); 2) alterations in metabolites involved in carbohydrate and gut microbiota metabolism, inflammation and oxidative stress (metabolic syndrome), some of them shared with schizophrenia; 3) alterations of cytokines secreted by adipose tissue, phosphatidylcholines, acylcarnitines, Sirtuin 1, orexin-A, and changes in microbiota composition (antipsychotic-induced metabolic syndrome). Conclusion: Novel insights into the pathogenesis of schizophrenia and metabolic side-effects associated with its antipsychotic treatment represent an urgent request for scientists and clinicians. Leptin, carnitines, adiponectin, insulin, or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like metabolomics have the power to strengthen research for achieving preventive, diagnostic, and therapeutical solutions for schizophrenia.

Lurasidone is a novel azapirone derivative and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5- HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acted on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Administered with food or within 30 minutes from a meal, it presents sufficient bioavailability and does not interact with most of the other drugs during metabolism. With little effects on hormones and weight gain, potential procognitive profile due to its 5-HT7 antagonism, and reduced extrapyramidal side effects, lurasidone could be a good choice in terms of both effectiveness and tolerability, particularly for patients headed towards a long-term treatment. This article aims to summarize the available scientific evidence from the literature on the use of lurasidone in children and adolescents and to provide recommendations for clinical management and future research.

Atypical antipsychotic depot medications are currently recommended for patients with schizophrenia (SCZ) to prevent relapse and ameliorate the long-term prognosis of these patients. This review critically summarizes the available data about the association between the plasma concentrations of long-acting Second- Generation Antipsychotics (SGAs) and the clinical effectiveness of these compounds in patients affected by SCZ or schizoaffective disorder. Our question is if the measurement of these concentrations can be helpful for clinicians in predicting treatment response and clinical stabilization of patients. Bibliographic research on the main databases was performed, and 13 studies were finally included in this review. Contrasting results were found between plasma concentrations of long-acting injectable (LAI) risperidone and clinical amelioration according to rating scale scores. Data are too scanty to draw conclusions for olanzapine and paliperidone. In contrast, despite small sample sizes, data are quite concordant in showing a relation between long-acting SGA plasma concentrations and D2 receptor occupancy. Despite the preliminary encouraging results, particularly for D2 receptor occupancy, future research with larger samples will have to confirm the clinical usefulness of measuring LAI SGA plasma concentrations to predict the clinical response of patients affected by severe mental conditions such as SCZ.

Background: The evaluation of long-term effectiveness and tolerability of aripiprazole once-monthly (AOM) is yet scarce, and severely ill patients have not been specifically studied. Objective: The aim of the study was to explore the long-term adherence, effectiveness and tolerability of AOM in the treatment of patients with severe (Clinical Global Impression-Severity, CGI-S ≥ 5) schizophrenia, and whether high-dose therapy may benefit patients inadequately controlled on standard doses. Methods: Six-year mirror-image study, with a 36-month prospective follow-up, was conducted on patients with severe schizophrenia who underwent treatment with AOM (n = 60). The assessment included the CGI-S, the WHO Disability Assessment Schedule (WHO- DAS), the Medication Adherence Report Scale (MARS), the laboratory tests, the assessment of weight and adverse effects reported. Reasons for treatment discontinuation, hospital admissions and psychiatric medications in the previous three years and during the follow-up were recorded. Results: The average dose was found to be 780 (120) mg/28 days. Tolerability was good, with fewer side effects or biological parameters alterations reported. There were three discharges due to adverse effects, two due to lack of effectiveness and one treatment abandoning. Weight and prolactin levels were decreased. CGI-S and WHO-DAS were decreased (p < 0.001), and MARS increased (p < 0.001). There were less treatment abandoning, hospital admissions (p < 0.0001) and concomitant medication (p < 0.01) observed than during the previous 36 months. Conclusion: Treatment adherence and tolerability of AOM were found to be remarkable, even in those patients on high doses. AOM showed effectiveness in patients with severe schizophrenia, who recorded less hospitalizations and clinical severity and disability, although a considerable percentage of them required higher doses than labeled.

Nanoparticles (NPs) are projected to play a significant role in the fight against coronavirus disease (COVID-19). The various properties of NPs like magnetic and optical can be exploited to build diagnostic test kits. The unembellished morphological and physiochemical resemblances of SARS-CoV-2 with synthetic NPs make them a potent tool for mediation. Nanoparticles can be analytically functionalized with different proteins, polymers, and functional groups to perform specific inhibitory functions, while also serving as delivery vehicles. Moreover, NPs can also be employed to prepare broad-spectrum respiratory drugs and vaccines that can guard seasonal flu and prepare the human race for the pandemic in the future. The present review outlines the role of NPs for detection, diagnostic and therapeutic purposes against members of the coronavirus family. We emphasize nanomaterial-based approaches to address coronaviruses in general and SARS-CoV-2 in particular. We discuss NPs based detection systems like graphene (G-FET), biosensors, and plasmonic photothermal associated sensors. The therapeutic approaches exploiting NPs such as inorganic, organic virus-like & self-assembly protein (VLP), and inactivation of SARS-CoV-2 employing photodynamic are also presented.

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.