Antipsychotic Research Articles

Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia.

Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia. ApoE-/- mice immunized with SFT2D2-peptides can be used as a model for testing immunotherapy in this subgroup of patients. We used the atypical antipsychotic drug clozapine and immunosuppressant rapamycin to test their effects in this mouse model. The mice were evaluated for cognitive and schizophrenia-like behaviors. Following behavioral testing, brain samples were collected for analyzing specific pathological changes and dendritic spine formation. Clozapine and rapamycin reversed impaired pre-pulse inhibition, motor impairment, and improved cognitive ability in ApoE -/- mice exposed to anti-SFT2D2 immunoglobulin G. Immunohistochemical assays revealed that both clozapine and rapamycin significantly reduced activated microglial infiltration and restored neuronal dendritic spine density. Our study results suggested that clozapine and rapamycin possess therapeutic benefits for managing autoimmune psychosis and provide mechanistic insights into immunotherapies involving immunosuppressive agents.

Studies on Risperidone Loaded β-Cyclodextrin Nanosponges for Managing Altered Mental Status and Delirium in Cancer Patients

This study explores the prospective of risperidone-loaded β-cyclodextrin nanosponges as a therapeutic strategy for managing altered mental status (AMS) and delirium in cancer patients. Almost 87% of patients with advanced cancer experience AMS or delirium, significantly impacting prognosis and quality of life. The present study aims to enhance the solubility, bioavailability, and therapeutic effectiveness of second-generation antipsychotic medication risperidone (RSP), with poor aqueous solubility, it was encapsulated in β-cyclodextrin nanosponges. The nanosponges prepared by fusion technique using different β-CD: DPC molar ratios, were tested for their ability to encapsulation efficiency, drug loading, and dissolutions kinetics. Batch 1, (1:1 molar ratio) exhibits RSP loading capacity (454.2 µg/mg) and encapsulation efficiency (90.84%) along with DSC and FTIR also confirmed that the RSP was successfully encapsulated and without any chemical interactions. In vitro dissolution studies demonstrated a biphasic release profile, with an initial burst followed by sustained release, governed by Fickian diffusion as confirmed by release kinetics modeling. The improved solubility and dissolution profile of the nanosponges will be significant to improve risperidone delivery, ensuring better symptom management in a vulnerable population. These findings highlight the potential of β-cyclodextrin nanosponges as an innovative and adaptable platform for enhancing antipsychotic drug delivery.

Autoimmune Encephalitis in Catatonic and Treatment-Resistant Psychotic Patients Referred to Electroconvulsive Therapy: Two Case Reports and Systematic Review.

Autoimmune encephalitis (AE) tends to manifest as a mixture of neuropsychiatric and somatic symptoms, either of which may predominate, and often shows a progressive clinical course sometimes leading to life-threatening conditions. Catatonic and psychotic syndromes, regardless of whether associated with dysautonomia, are common manifestations of AE, especially concerning the anti-NMDAR subtype. Several autoantibodies targeting different neuronal epitopes have been linked to specific clinical manifestations and their detection is embedded in some of the diagnostic criteria for AE. Therapeutical management of AE is challenged by limited diagnostic abilities and poor understanding of the underlying pathophysiology for most of its subtypes. Although the prompt delivery of disease-modifying therapies represents the cornerstone of treatment and primarily affects prognosis, less is known about the role of symptom specific supportive measures like electroconvulsive therapy (ECT). Based on a systematic review of 26 patient-level descriptions of individuals, each with a diagnosis of AE treated with ECT, a favorable clinical response was found in more than ¾ of the revised cases (76.9%). The most common indications for ECT administration were catatonic and psychotic syndromes, often nonresponsive to prior pharmacotherapy with benzodiazepines, antipsychotic, and other psychotropic drugs. Noteworthy side effects were only reported for 3 of 26 patients. Though the low number of cases and publication bias should be considered as major limitations, current available reports are in support of the inclusion of ECT in the integrated therapeutic algorithm of AE to address psychiatric conditions such as severe psychosis and catatonia.

The Past and Present of Schizophrenia

Schizophrenia is a severe mental disorder and one of the most challenging psychiatric diseases to treat clinically. Modern medical treatment for schizophrenia primarily relies on antipsychotic medications, but issues such as side effects and drug resistance remain significant challenges in treatment. This review systematically examines the etiology, clinical symptoms, treatment methods, and rehabilitation strategies for schizophrenia, explores the advantages and shortcomings of current treatment options, and, based on the latest research findings, proposes future directions for research and clinical treatment.

Identification of serum metabolic traits of AIWG in first-episode schizophrenia patients.

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic drugs and may lead to cardiometabolic comorbidities. There is an urgent public health need to identify patients at high risk of AIWG and determine potential biomarkers for AIWG. In the Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) trail, first-episode schizophrenia patients were randomly assigned to olanzapine, risperidone, perphenazine, amisulpride or aripiprazole for 8 weeks. We applied absolute quantitative lipidomics at baseline and after 8 weeks of antipsychotic treatment in 80 patients. To evaluate the effects of AIWG on lipid profile, 25 patients with ≥ 7% weight changes (weight gain, WG) and 28 patients with <|3|% weight changes (weight stable, WS) were investigated, separately. We found that baseline CerP(d40:3) and PC(20:1_22:6) were positively associated with weight changes at follow-up (r > 0.4, pFDR < 0.05). Additionally, baseline CerP(d40:3) and PC(20:1_22:6) independently predicted rapid weight gain, with receiver operating curve (ROC) of 0.76 (95% CI: 0.63-0.90), and 0.75 (95% CI: 0.62-0.88), respectively. Compared with baseline, levels of 45 differential lipid metabolites (fold change > 1.2, VIP > 1 and pFDR < 0.05) were significantly higher in the WG group. Interestingly, no differential lipid metabolites were identified in the WS group. The LASSO regression model identified 18 AIWG lipid signatures, including 2 cholesterol esters (ChEs), 1 diglyceride (DG), 12 phosphatidylcholines (PCs), 1 phosphatidylglycerol (PG), 1 phosphatidylinositol (PI), and 1 sphingomyelin (SM), with the ChE(16:1) contributing the most. Furthermore, the level changes of ChE(16:1) were positively associated with weight gain(r = 0.67, pFDR < 0.05). Our findings indicate that lipid profile may serve as predictors of rapid weight gain in schizophrenia and provide useful markers for AIWG intervention.

Exploring the effects of probiotics on olanzapine-induced metabolic syndrome through the gut microbiota

BackgroundMaintaining gut microbial homeostasis is crucial for human health, as imbalances in the gut microbiota (GM) can lead to various diseases, including metabolic syndrome (MS), exacerbated by the use of antipsychotic medications such as olanzapine (OLZ). Understanding the role of the GM in OLZ-induced MS could lead to new therapeutic strategies. This study used metagenomic analysis to explore the impact of OLZ on the GM composition and examined how probiotics can mitigate its adverse effects in a rat model. Changes in weight, blood pressure, and lipid levels, which are key parameters defining MS, were assessed. Additionally, this study investigated serotonin, dopamine, and histopathological changes to explore their possible link with the microbiota-gut-brain axis (MGBA).ResultsOLZ had an antagonistic effect on serotonin and dopamine receptors, and it was consistently found to alter the composition of the GM, with an increase in the relative abundance (RA) of the Firmicutes/Bacteroidetes phyla ratio and TM7 genera, indicating that the anticommonsal action of OLZ affects appetite and energy expenditure, contributing to obesity, dyslipidemia and increased blood pressure, which are core components of MS. Hepatic steatosis and intestinal damage in OLZ-treated rat tissues further indicate its role in MS. Conversely, the administration of probiotics, either alone or in combination with OLZ, was found to mitigate these OLZ-induced symptoms of MS by altering the GM composition. These alterations included increases in the abundances of the taxa Bacteroidetes, Actinobacteria, Prevotella, Blautia, Bacteroides, Bacteroidales, and Ruminococcaceae and a decrease in Firmicute abundance. These changes helped maintain gut barrier integrity and modulated neurotransmitter levels, suggesting that probiotics can counteract the adverse metabolic effects of OLZ by restoring the GM balance. Moreover, this study highlights the modulation of the MGBA by OLZ as a potential mechanism through which probiotics modulate serotonin and dopamine levels, influencing metabolic health.ConclusionThese findings emphasise the significant impact of OLZ on the GM and its contribution to MS. These findings suggest that interventions targeting the GM, such as probiotics, could mitigate the metabolic side effects of OLZ. Future research should focus on developing integrative treatment approaches that consider the health of the gut microbiome in managing antipsychotic-induced adverse effects.

Clozapine rechallenge following myocarditis: a systematic review of rechallenge cases.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge. A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies. Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge. The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Systematic review of long-acting injectable antipsychotic medications approved from 2008 to october 2024 and agents in phase 3.

The purpose of this systematic review is to provide a detailed summary of the long-acting injectable antipsychotic medications approved by the Food and Drug Administration (FDA) between 2008 to October 2024. We aim to provide an overview of the mechanism of action, indications for both labeled and off-label uses, evidence for efficacy, dosing, and the adverse effects of each drug. Studies published from 2008 to October 1, 2024, were identified from the PubMed database, using the keywords: 'long-acting injectables' OR 'LAI*'AND 'psychopharm*" OR 'schizophrenia' The authors conducted a focused analysis independently and reached a consensus on the recently approved long-acting injectable antipsychotic medications to be included in this systematic review. Key findings were derived from the full text in order to create the tables from selected studies. A total of 13 long-acting injectable antipsychotic medications for the treatment of schizophrenia were FDA-approved between 2008 and October 1, 2024. One long-acting injectable antipsychotic is currently being investigated in a Phase 3 clinical trial. The indications, evidence, practical implementation issues, and adverse effects of each drug are discussed in this review. Improved understanding of newly approved long-acting injectables is critical in the management of patients with schizophrenia. The FDA approval of long-acting injectables in the past 15 years creates hopeful options for clinicians to improve clinical outcomes and quality of life for their patients.

Addressing brain metabolic connectivity in treatment-resistant schizophrenia: a novel graph theory-driven application of 18F-FDG-PET with antipsychotic dose correction

Few studies using Positron Emission Tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) have examined the neurobiological basis of antipsychotic resistance in schizophrenia, primarily focusing on metabolic activity, with none investigating connectivity patterns. Here, we aimed to explore differential patterns of glucose metabolism between patients and controls (CTRL) through a graph theory-based approach and network comparison tests. PET scans with 18F-FDG were obtained by 70 subjects, 26 with treatment-resistant schizophrenia (TRS), 28 patients responsive to antipsychotics (nTRS), and 16 CTRL. Relative brain glucose metabolism maps were processed in the automated anatomical labeling (AAL)-Merged atlas template. Inter-subject connectivity matrices were derived using Gaussian Graphical Models and group networks were compared through permutation testing. A logistic model based on machine-learning was employed to estimate the association between the metabolic signals of brain regions and treatment resistance. To account for the potential influence of antipsychotic medication, we incorporated chlorpromazine equivalents as a covariate in the network analysis during partial correlation calculations. Additionally, the machine-learning analysis employed medication dose-stratified folds. Global reduced connectivity was detected in the nTRS (p-value = 0.008) and TRS groups (p-value = 0.001) compared to CTRL, with prominent alterations localized in the frontal lobe, Default Mode Network, and dorsal dopamine pathway. Disruptions in frontotemporal and striatal-cortical connectivity were detected in TRS but not nTRS patients. After adjusting for antipsychotic doses, alterations in the anterior cingulate, frontal and temporal gyri, hippocampus, and precuneus also emerged. The machine-learning approach demonstrated an accuracy ranging from 0.72 to 0.8 in detecting the TRS condition.

Effect of antipsychotic on mismatch negativity amplitude and evoked theta power in drug-naïve patients with schizophrenia

BackgroundRecurrent observations have indicated the presence of deficits in mismatch negativity (MMN) among schizophrenia. There is evidence suggesting a correlation between increased dopaminergic activity and reduced MMN amplitude, but there is no consensus on whether antipsychotic medications can improve MMN deficit in schizophrenia.MethodsWe conducted clinical assessments, cognitive function tests, and EEG data collection and analysis on 31 drug-naïve patients with schizophrenia. Comprehensive evaluation tools such as PANSS and MCCB. MMN amplitude was analyzed by event-related potential (ERP) approaches, evoked theta power was analyzed by event-related spectral perturbation (ERSP) approaches.ResultsOur findings indicate that antipsychotic treatment significantly improved clinical symptoms, as evidenced by reductions in PANSS positive, negative, general symptoms, and total scores (all p < 0.001). Cognitive function improvements were observed in language learning, working memory, and overall MCCB scores (p < 0.05), although other cognitive domains showed no significant changes. However, no significant improvements were noted in MMN amplitude and evoke theta power after four weeks of antipsychotic treatment (p > 0.05).ConclusionThese results suggest that while antipsychotic medications effectively alleviate clinical symptoms, their impact on MMN amplitude and evoke theta power deficit is limited in the short term. Moreover, the amelioration of cognitive impairment in individuals with schizophrenia is not readily discernible, and it cannot be discounted that the enhancement observed in language acquisition and working memory may be attributed to a learning effect. These findings underscore the complexity of the neurobiological mechanisms involved and highlight the need for further research to optimize individualized treatment strategies for schizophrenia.Trial RegistrationChiCTR2000038961, October 10, 2020.

Drug-Induced Myocardial Infarction: A Review of Pharmacological Triggers and Pathophysiological Mechanisms.

Myocardial infarction (MI) is a significant cardiovascular event caused by the decrease in or complete cessation of blood flow to a portion of the myocardium. It can arise from a variety of etiological factors, including pharmacological triggers. This review aims to explore the diverse drugs and substances that might lead to drug-induced myocardial infarction, focusing on their mechanisms of action and the pathophysiological processes involved. Various established and emerging pharmacological agents that could elevate the risk of myocardial infarction, such as nonsteroidal anti-inflammatory drugs, hormonal therapies, anticoagulants, and antipsychotic medications, are discussed. The role of drug-induced endothelial dysfunction, coronary artery spasm, and thrombosis are presented in order to highlight the underlying mechanisms. This review emphasizes the need for increased awareness among healthcare professionals to mitigate the risks associated with different pharmacological therapies to improve patient outcomes.

Atypical antipsychotic drug olanzapine inhibits 5-HT3 receptor-mediated currents by allosteric and non-competitive mechanisms.

Olanzapine, an atypical antipsychotic, is widely used in the treatment of schizophrenia and bipolar disorder due to its modulation of dopamine and serotonin receptor systems. While its primary action involves antagonism of dopamine D2 and serotonin 5-HT (5-hydroxytryptamine)2A receptors, recent evidence suggests that olanzapine also inhibits 5-HT3 receptors, which are ligand-gated ion channels involved in synaptic transmission in central and peripheral nervous systems. The present study aimed to investigate the action of olanzapine on 5-HT3 receptor-mediated currents using whole-cell voltage-clamp recordings in NCB-20 neuroblastoma cells. Results of this study indicated that olanzapine could act as a non-competitive antagonist of the 5-HT3 receptor, exhibiting concentration-dependent inhibition of ion currents. Moreover, olanzapine facilitated both deactivation and desensitization kinetics, accelerating decay of 5-HT3 receptor-mediated currents. Recovery from desensitization was significantly delayed by olanzapine, whereas recovery from deactivation was largely unaffected by it. Current-voltage relationship analysis revealed that olanzapine reduced the amplitude of 5-HT3 receptor-mediated currents across all holding potentials without altering reversal potential, suggesting a voltage-independent inhibition. Furthermore, olanzapine exhibited use-dependent inhibition, with a greater reduction in current observed during more frequent 5-HT application. These findings provide novel insights into a non-competitive and allosteric inhibition of 5-HT3 receptors by olanzapine, contributing to a deeper understanding of its pharmacological profile in neuropsychiatric and gastrointestinal conditions where serotonergic neurotransmission is implicated.

Pimozide Inhibits Type II but Not Type I Hair Cells in Chicken Embryo and Adult Mouse Vestibular Organs.

Pimozide is a conventional antipsychotic drug of the diphenylbutylpiperidine class, widely used for treating schizophrenia and delusional disorders and for managing motor and phonic tics in Tourette's syndrome. Pimozide is known to block dopaminergic D2 receptors and various types of voltage-gated ion channels. Among its side effects, dizziness and imbalance are the most frequently observed, which may imply an effect of the drug on the vestibular sensory receptors, the hair cells. Amniotes possess two classes of vestibular hair cells, named type I and type II hair cells, which differ in terms of signal processing and transmission. We previously reported that Pimozide [3 μM] significantly increased a delayed outward rectifying K+ current (IK,V). In the present study, using the whole-cell patch-clamp technique we additionally show that Pimozide decreases the inward rectifying K+ current (IK,1) and the mixed Na+/K+ current (Ih) of chicken embryo type II hair cells, whereas it does not affect type I hair cells' ionic currents. Since ion channels' expression can vary depending on age and animal species, in the present study, we also tested Pimozide in adult mouse vestibular hair cells. We found that, like in the chicken embryo, Pimozide significantly increases IK,V and decreases IK,1 and Ih in type II hair cells. However, in the adult mouse, Pimozide also slightly increased the outward rectifying K+ current in type I hair cells. While providing a possible explanation for the vestibular side effects of Pimozide in humans, its inhibitory action on mammalian hair cells might be of interest for the local treatment of vestibular disorders characterized by altered vestibular input, like Ménière's disease.

Evaluation of droperidol use in the emergency department: a retrospective analysis of QTc prolongation and adverse events

BackgroundDroperidol is a first-generation antipsychotic medication that has been used for various indications in the emergency department (ED); however, its use has been controversial due to reports of QT prolongation and the risk of torsades de pointes (TdP). The aim of the study is to evaluate the safety of droperidol administration in the ED.MethodsThis was a retrospective study, conducted at an academic level I trauma center. System-generated reports were used to identify all droperidol administrations in the ED from the time that droperidol was reintroduced to the institutional formulary on July 1, 2019 through January 31, 2023. The major safety endpoint was a composite of the incidence of QTc interval prolongation, incidence of TdP, ventricular arrhythmia, or hypotension.ResultsA total of 327 administrations of droperidol were identified in 245 patients in the ED. The composite safety endpoint occurred in 30 (9.1%) administrations. None of these events were classified as “probable” or “definite” on the Naranjo adverse drug reaction probability scale. No episodes of TdP or serious ventricular arrhythmia were reported. Higher cumulative droperidol dose and creatinine clearance < 60 mL/min were associated with an increased odds of developing QTc prolongation (OR 1.27 [CI 1.04–1.56]) and (OR 1.01 [CI 1.0-1.02]), respectively.ConclusionsThe study supports the use of low dose droperidol for various indications in the ED. There were no serious adverse events reported that could be directly attributed to droperidol use; however, it is crucial to consider the potential dose dependent impact on QTc prolongation.

The limited clinical utility of a routine creatine kinase (CK) on admission to a psychiatric inpatient unit

BackgroundCreatine kinase (CK) is an intracellular enzyme expressed most commonly in tissues such as skeletal muscle. CK can be used as an investigation to support the diagnosis of conditions such as neuroleptic malignant syndrome (NMS), a rare idiosyncratic drug reaction – classically to antipsychotic medications – which can be fatal. Routine screening of CK in psychiatric inpatients is a known practice, but its value is uncertain. We aimed to ascertain whether such screening resulted in new diagnoses of NMS or other conditions, and changes in clinical management.MethodsUsing an electronic case register, we conducted a descriptive retrospective cohort study, identifying all psychiatric inpatient admissions in a South London mental health trust over a four-year period where a CK test was conducted within 48 h of admission. We extracted the demographic and clinical characteristics (e.g., diagnosis) of those who met inclusion criteria. Free-text review was performed on all those with a CK potentially suggestive of NMS (CK ≥ 4x upper limit of normal reference range (ULN)) to determine the impact of this abnormal result on subsequent management and diagnosis (including NMS if identified).ResultsOf 14,236 inpatient episodes in the specified window, 2358 (16.6%) had a CK test within 48 h of admission. This was ≥ 4x ULN in 327 (13.8%) cases (free-text successfully reviewed in 318). There were no cases of NMS identified. An abnormal CK result led to a new alternative diagnosis, such as dehydration or catatonia, in only 14 patients (4.4% raised CK sample, 0.6% total CK sample). Impact on subsequent management appeared limited, with the most common adjustment being an increase in frequency of physical observations in 47 instances (14.8%).ConclusionsThe clinical utility of untargeted screening using a serum CK for psychiatric inpatients appears limited, with poor specificity in detection of NMS and a minimal impact on subsequent clinical management.

Risk of long-term post-stroke dementia using a linked dataset of patients with ischemic stroke without a history of dementia.

Post-stroke dementia (PSD) is a common and disabling sequela of stroke. However, the long-term incidence of PSD after an ischemic stroke and factors which predict its occurrence are incompletely understood. Linkage of large health datasets is being increasing used to study long term outcomes after disease. We used large scale linked data from Korea to determine the long-term incidence of PSD after ischemic stroke, and identify which factors predicted it occurrence. From January 2008 to December 2014, patients with ischemic stroke (n=37,553) without a history of dementia were included in a linked dataset comprising the claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data. The outcome measure was PSD after ischemic stroke. Clinical factors evaluated included vascular risk factors, acute stroke management including reperfusion therapy, antithrombotics, and statins, stroke severity, and educational levels, were evaluated. Results: Among 37,553 patients with ischemic stroke without a history of dementia (mean age: 64.9 years; 61.9% males), 6,052 (16.1%) experienced PSD during a median follow-up period of 5 (interquartile range 3.4-7.0) years. The 10 year estimated cumulative incidence of dementia was 23.5%. Age [hazard ratio (HR) 1.82 per 10 years, 95% confidence interval (CI) 1.75-1.88] and a lower educational level [illiteracy or no education HR 1.65 (CI, 1.44-1.88), 0-3 years 1.53 (CI, 1.31-1.79), 4-6 years 1.60 (CI, 1.43-1.80), 7-9 years 1.32 (CI, 1.16-1.49), 10-12 years 1.17 (CI, 1.04-1.32)] were independently associated with an elevated risk of PSD. Male sex was associated with a significantly lower risk of PSD (HR 0.86, CI 0.79-0.92). Diabetes mellitus (HR 1.21, CI 1.14-1.29), a history of stroke before index stroke (HR 1.31, CI 1.21-1.41), and initial National Institutes of Health Stroke Scale (HR 1.03, CI 1.03-1.04) were independent risk factors for PSD. Regarding medications, the use of anticoagulation and antipsychotic medications after stroke appeared to be associated with increased PSD risk whereas statin therapy was associated with a reduced risk. PSD is common with a 5 and 10 year incidence in patients with ischemic stroke without a history of dementia of 16.1% and 23.5% respectively. Factors associated with PSD include age, female sex, lower educational level, diabetes mellitus, initial stroke severity, antipsychotics and anticoagulants. Further studies are required to determine whether reducing those risk factors which are treatable reduces the incidence of PSD.

Behavioral symptoms and treatment challenges for patients living with dementia: Hospice clinician and caregiver perspectives.

Dementia affects one in three older adults over age 85 and individuals with dementia constitute the fastest growing population of patients entering hospice care. While cognitive impairment is the hallmark of dementia, behavioral symptoms are reported in nearly all patients with advanced dementia, contributing to both the complexity of end-of-life care and caregiver burden. This qualitative study involved semi-structured interviews with prescribing hospice clinicians and caregivers of patients living with dementia who previously received hospice services. Interviews included questions regarding common behavioral symptoms observed at end of life, side effects of benzodiazepine and antipsychotic medications, perceived effectiveness of medications used, and non-pharmacologic treatment strategies. Data from audio-recorded sessions were transcribed, coded to identify relevant concepts, and reduced to determine major themes. A total of 23 hospice clinicians and 20 family caregivers participated in interviews. Agitation, including physical and verbal aggression, irritability, and anger, was identified as the most concerning behavioral symptom of dementia at end of life; when discussing agitation, clinicians focused on the safety of the patient living with dementia and others, while caregivers were concerned because they perceived it as a change in personality of their loved one. When using antipsychotics and benzodiazepines to address behavioral symptoms, caregivers viewed sedation as a concerning side effect, while clinicians were less concerned and noted this as an anticipated outcome of treatment. Overall, family caregivers perceived medications as more effective than clinicians. Finally, non-pharmacologic interventions are generally preferred over pharmacologic treatments, but were reported as difficult to implement. Study findings can help to inform dialogue between hospice clinicians and caregivers regarding anticipated behavioral changes, as well as risks, benefits, and limitations of medication treatment options for behavioral symptom management. Further work is needed to understand the appropriate level of use of psychotropic medications for end-of-life dementia care.

Modern approaches to the therapy of schizophrenia with atypical neuroleptics (based on clinical observations)

According to the lack of sufficient scientific data on the ratio, severity, and clinical pathomorphism of positive and negative symptoms in schizophrenia, a more detailed research of this issue is required. The ratio of positive and negative disorders in the structure of schizophrenia spectrum disorders is different in each specific case.It is known that problems associated with the formation of stable remission in schizophrenia significantly affect the functional well-being, quality and life expectancy of patients. To ensure comprehensive, effective and safe treatment of patients with schizophrenia antipsychotic drugs with a broad spectrum of action are needed. Cariprazine is one of the more effective antipsychotics, both in relation to positive symptoms and in relation to negative and cognitive symptoms.This paper presents a number of clinical observations that demonstrate the efficacy of the third-generation neuroleptic cariprazine as a potent antipsychotic drug with a favorable safety profile, providing high adherence to therapy and successfully used both in patients with the first psychotic episode and in patients with a disorder duration of more than five years. Also, the complex therapy schemes with psychosocial rehabilitation measures in the inpatient and outpatient departments of the Psychosocial Rehabilitation Center, located on the basis of the Regional Clinical Psychiatric Hospital, are described in detail.

An Investigation of Antipsychotic Activity of Plant Extracts in Experimental Animals

The current study is done on plant extracts as antipsychotic medication in ayurvedic formulation. The hallucinations are induced by electro shock therapy or apomorphine. After induction of hallucinations the plant extract is administered as standard group, control group and simple group of six albino rats and the results are screened and analyzed with standard drug comparision. Pre-treatment of MEIR (methanolic extract of Ipomoea reniformis) for 15days at the dose of 200 and 400 milligram per kilogram body weight was used to evaluate antipsychotic activity. The antipsychotic activity was also studied against Apomorphine induced stereotype behavior in rats, Pilocarpine induced purposeless chewing in rats and Apomorphine induced climbing behavior in mice. In pre-treatment studies of antipsychotic activity, MEIR at the dose of 200 and 400 milligram per kilogram body weight significantly (p&lt;0.001) reduced the stereotyped behavior against Apomorphine induced stereotypy behavior model. In Pilocarpine induced purposeless chewing behavior, MEIR at the dose of 200 and 400 milligram per kilogram body weight significantly (p&lt;0.01) decreased chewing behavior and in Apomorphine induced climbing behavior, MEIR significantly (p&lt;0.001) reduced the climbing activity at the dose of 200 and 400 milligram per kilogram body weight. The results of the Pr (+) study suggest that the MEIR possess antipsychotic activity in rats and mice. The results of each activites are compared with standard medicament and evaluated. Keywords: Ipomoea reniformis, apomorphine, locust bean gum, pilocarpine, hallucinations, antipychotic activity

Drug-induced megacolon in schizophrenia: a pharmacovigilance study of antipsychotic medications from the Japanese Adverse Drug Event database: a disproportionality analysis

ABSTRACT Background Megacolon, characterized by colon dilation due to a nerve plexus disorder, can be fatal if untreated. Antipsychotic drugs for schizophrenia have anticholinergic effects that may cause chronic constipation and impaired gastrointestinal motility, potentially leading to megacolon. However, the megacolon risk associated with each antipsychotic drug has not been thoroughly evaluated. This study characterized the drug-induced megacolon using the Japanese adverse drug event database Methods A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report from April 2004 to April 2024. The study included 10,884 schizophrenia patients with, with 72 reports of antipsychotic-induced megacolon. Results Antipsychotic-induced megacolon was reported with 13 different antipsychotic drugs. Analysis of the reporting odds ratio for drug-induced megacolon for each antipsychotic revealed three drugs with statistically significant positive signals: zotepine = 7.25; sulpiride = 4.53; and quetiapine = 4.34. In addition, logistic regression analysis revealed that antipsychotic-induced megacolon is characterized by female sex. Conclusion Zotepine, sulpiride, and quetiapine are associated with antipsychotic-induced megacolon in schizophrenia patients, and it is suggested that there is a gender difference. This study provides novel evidence for evaluating adverse drug events related to schizophrenia pharmacotherapy, contributing to improved quality of life for these patients.