Protocol on to Assess the Effectiveness of Planned Teaching on Knowledge Regarding to Adverse Effect of Antipsychotic Agents among Caregivers of Schizophrenia Patient

Background of the Study: The involvement of caregivers in treatment has been known as a vital part of mental health care. The enlarged emphasis on caregiver partaking has been to some extent driven by the shift from hospitals to primary provision of schizophrenia care in the community, where caregivers are more broadly involved in supporting consumers. Objectives: 1. To assess the pre-test knowledge regarding adverse effect of antipsychotic agent among caregivers of schizophrenia patients 2. To evaluate the effectiveness of planed teaching programme on knowledge regarding to antipsychotic agent among caregiver of schizophrenia patients. 3. To find out the association between post-test knowledge score with regards to adverse effect of antipsychotic agent regarding to adverse effect among caregivers of schizophrenia patients. Material and Methods: Pre-experimental, one group pretest and post-test design to assess the effectiveness of planed teaching on knowledge regarding adverse effect of antipsychotic agents and their response during the adverse effect among caregivers of schizophrenia patients. In this study total 100 caregivers of schizophrenia patient who full fill the inclusion criteria. Expected Results: This study is planned to assess the effectiveness of planed teaching on knowledge regarding to adverse effect of antipsychotic agents among caregivers of schizophrenia patients. There will be significant association between pre-test and post-test knowledge with regards to antipsychotic agents among schizophrenia patient’s caregivers. Conclusion: The conclusion will be drawn from the outcomes.

Effects of an Atypical Antipsychotic, Zotepine, on Astroglial L-Glutamate Release through Hemichannels: Exploring the Mechanism of Mood-Stabilising Antipsychotic Actions and Antipsychotic-Induced Convulsion

Accumulating neuropsychopharmacological evidence has suggested that functional abnormalities of astroglial transmission and protein kinase B (Akt) contribute to the pathophysiology and/or pathomechanisms of several neuropsychiatric disorders, such as epilepsy, schizophrenia, affective disorders and antipsychotic-induced convulsions. Therefore, to explore the pathophysiology of mood-stabilising antipsychotics and the proconvulsive actions of atypical antipsychotics, the present study determined the effects of a mood-stabilising, atypical, antipsychotic agent, zotepine (ZTP), on astroglial L-glutamate release and the expression of connexin43 (Cx43) protein in cortical, primary, cultured astrocytes using ultra-high-pressure liquid chromatography and capillary immunoblotting systems. Both acute and subchronic administrations of therapeutically relevant concentrations of ZTP did not affect astroglial L-glutamate release or Cx43 expression in plasma membranes; however, chronic administration of a therapeutically relevant concentration of ZTP increased astroglial L-glutamate release and Cx43 expression in the plasma membrane. Subchronic administrations of a supratherapeutic concentration of ZTP enhanced astroglial L-glutamate release and Cx43 expression in the plasma membrane, whereas acute administration of a supratherapeutic concentration of ZTP enhanced astroglial L-glutamate release without affecting Cx43 expression. These stimulatory effects of ZTP on astroglial L-glutamate release through activated hemichannels and Cx43 trafficking to the astroglial plasma membrane were suppressed by the Akt inhibitor. These results suggest that ZTP enhances astroglial L-glutamate release in a concentration-dependent and time-dependent manner due to the enhanced function of astroglial hemichannels, probably via activation of Akt signalling. Therefore, the enhanced astroglial L-glutamatergic transmission induced by ZTP is, at least partially, involved in the mood-stabilising antipsychotic and proconvulsive actions of ZTP.

The effects of galangin in prepulse inhibition test and experimental schizophrenia models

Objective: Acetylcholinesterase inhibitors are the focus of interest in the management of schizophrenia. We aimed to investigate the effects of acute galangin administration, a flavonoid compound with acetylcholinesterase inhibiting activity, on schizophrenia-associated cognitive deficits in rats and schizophrenia models in mice. Methods: Apomorphine-induced prepulse inhibition (PPI) disruption for cognitive functions, nicotinic, muscarinic and serotonergic mechanism involvement, and brain acetylcholine levels were investigated in Wistar rats. Apomorphine-induced climbing, MK-801-induced hyperlocomotion, and catalepsy tests were used as schizophrenia models in Swiss albino mice. The effects of galangin were compared with acetylcholinesterase inhibitor donepezil, and typical and atypical antipsychotics haloperidol and olanzapine, respectively. Results: Galangin (50,100 mg/kg) enhanced apomorphine-induced PPI disruption similar to donepezil, haloperidol, and olanzapine (p<0.05). This effect was not altered in the combination of galangin with the nicotinic receptor antagonist mecamylamine (1 mg/kg), the muscarinic receptor antagonist scopolamine (0.05 mg/kg), or the serotonin-1A receptor antagonist WAY-100635 (1 mg/kg) (p>0.05). Galangin (50,100 mg/kg) alone increased brain acetylcholine concentrations(p<0.05), but not in apomorphine-injected rats (p>0.05). Galangin (50 mg/kg) decreased apomorphine-induced climbing and MK-801-induced hyperlocomotion similar to haloperidol and olanzapine (p<0.05), but did not induce catalepsy, unlike them. Conclusion: We suggest that galangin may help enhance schizophrenia-associated cognitive deficits, and nicotinic, muscarinic cholinergic and serotonin-1A receptors are not involved in this effect. Galangin also exerted an antipsychotic-like effect without inducing catalepsy and may be considered as an advantageous antipsychotic agent.

Clinical outcomes of paliperidone long-acting injection in patients with schizophrenia: a 1-year retrospective cohort study

Background Schizophrenia is a severe psychiatric disorder. Poor medical adherence increases relapse rate. Long-acting injection of antipsychotic agent is developed for improving medical adherence. In this study, we examined the effect of paliperidone long-acting injection (PLAI) treatment in patients with schizophrenia in a real-world setting. Methods In this retrospective cohort study, 467 patients with schizophrenia were enrolled, treated with risperidone PLAI or oral antipsychotics, and followed for 1 year. Concomitant medication, namely anticonvulsants, antidepressants, anxiolytics, sedatives or hypnotics, anticholinergics, and beta-blockers, were administered. Patients were classified into 2 groups: the LAI group (patients received LAI for treatment) and the NLAI group (patients taking only oral antipsychotics). The incidence of hospitalization, the length of hospitalization, and the incidence of emergency room visits were assessed. Results The LAI group had a higher incidence of psychiatric acute ward admission (NLAI group = 4.8%; LAI = 30.3%) and emergency room visits (NLAI group = 7.3%; LAI group = 36.0%) before enrolment. During the one-year follow-up, the incidence of acute ward admission and emergency room visit did not differ in the NLAI group (P = .586 and .241) compared with before enrolment, whereas both incidences were significantly decreased in the LAI group (P < .0001 in both of them). Conclusions PLAI reduces the incidence of admission and emergency room visits.

The Efficacy of Olanzapine-Contained Antiemetic Therapy for Breast Cancer Patients: A Systematic Review and Pooled Analysis

Purpose: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. However, olanzapine is rarely used in the real-world antiemetic strategies for breast cancer patients who suffered chemotherapy-induced nausea and vomiting. Therefore, in this study, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled analyzed the results from clinical studies to confirm the efficacy of olanzapine in preventing nausea and vomiting in breast cancer.Methods: PubMed, Web of Science, EMBASE, and Cochrane Central databases were searched from inception through April 19, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate.Results: Five studies were identified in the systematic review, four of which with 466 breast cancer patients were included in the pooled analysis. In the acute period (0-24 hours), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group. While in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. Conclusion: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

Efficacy and safety of lurasidone in children and adolescents: Recommendations for clinical management and future research

: 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 acts 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 ith 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.

The therapeutic outcomes and adverse drug reactions study of Clozapine on Schizophrenia inpatients in the Grhasia psychiatric hospital Yogyakarta, Indonesia

Introduction: Clozapine is an antipsychotic agent used in schizophrenia recurrence or when other antipsychotics are not effective. Aims: This study aims to determine the therapeutic outcome and adverse drug reactions of clozapine in schizophrenia disorder among hospitalised patients. Methods: A retrospective cross-sectional study was conducted between January 2018 and December 2019 using inpatients’ medical records from the Grhasia Psychiatric Hospital, Yogyakarta. The therapeutic outcome was measured with the PANSS-EC scale, while adverse drug reactions of clozapine were analysed theoretically as per the literature. Results: The average decrease in the PANSS-EC score was 8.27, and the average duration to achieve this decrease was 2.5 days. The combination of typical-atypical antipsychotics could reduce the highest PANSS-EC score of 11-15 (41%). The adverse drug reactions of clozapine were tremor, weight gain, obesity, leucopenia, hyperglycemia, and hypercholesterolemia, among other effects. Conclusion: Clozapine is effective in improving positive and negative symptoms, but its use needs close monitoring.

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine

Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients’ medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan–Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93–0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97–7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01–1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.