Long-term Treatment Of Schizophrenia Research Articles

Clozapine suppresses NADPH oxidase activation, counteracts cytosolic H2O2, and triggers early onset mitochondrial dysfunction during adipogenesis of human liposarcoma SW872 cells

Long-term treatment of schizophrenia with clozapine (CLZ), an atypical antipsychotic drug, is associated with an increased incidence of metabolic disorders mediated by poorly understood mechanisms. We herein report that CLZ, while slowing down the morphological changes and lipid accumulation occurring during SW872 cell adipogenesis, also causes an early (day 3) inhibition of the expression/nuclear translocation of CAAT/enhancer-binding protein β and peroxisome proliferator-activated receptor γ. Under the same conditions, CLZ blunts NADPH oxidase-derived reactive oxygen species (ROS) by a dual mechanism involving enzyme inhibition and ROS scavenging. These effects were accompanied by hampered activation of the nuclear factor (erythroid-derived2)-like 2 (Nrf2)-dependent antioxidant responses compared to controls, and by an aggravated formation of mitochondrial superoxide. CLZ failed to exert ROS scavenging activities in the mitochondrial compartment but appeared to actively scavenge cytosolic H2O2 derived from mitochondrial superoxide. The early formation of mitochondrial ROS promoted by CLZ was also associated with signs of mitochondrial dysfunction. Some of the above findings were recapitulated using mouse embryonic fibroblasts.We conclude that the NADPH oxidase inhibitory and cytosolic ROS scavenging activities of CLZ slow down SW872 cell adipogenesis and suppress their Nrf2 activation, an event apparently connected with increased mitochondrial ROS formation, which is associated with insulin resistance and metabolic syndrome. Thus, the cellular events characterised herein may help to shed light on the more detailed molecular mechanisms explaining some of the adverse metabolic effects of CLZ.

Extrapyramidal adverse events and anticholinergics use after the long-term treatment of patients with schizophrenia with the new long-acting antipsychotic Risperidone ISM®: results from matching-adjusted indirect comparisons versus once-monthly formulations of Paliperidone palmitate and Aripiprazole monohydrate in 52-week studies

BackgroundRisperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting.MethodsA literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints.ResultsThe analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses.ConclusionsThis MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting.

Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

BackgroundAntipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking.MethodsWe will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework.DiscussionThis systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians.Systematic review registrationPROSPERO CRD42020175414

P.574 Safety of lurasidone 40-80mg/d in the long-term treatment of schizophrenia: a post hoc analysis of open label extension study

P.574 Safety of lurasidone 40-80mg/d in the long-term treatment of schizophrenia: a post hoc analysis of open label extension study

P.570 Effectiveness of lurasidone 40-80mg/d in the long-term treatment of schizophrenia: a post hoc analysis of 6-month, open-label extension study

P.570 Effectiveness of lurasidone 40-80mg/d in the long-term treatment of schizophrenia: a post hoc analysis of 6-month, open-label extension study

Negative Symptoms of Schizophrenia: New Prospects of Cariprazine Treatment.

Cariprazine is a new piperazine derivative atypical antipsychotic, like aripiprazole and brexpiprazole. It has been approved for treating schizophrenia in many countries and has recently been included on the List of Essential Medicines in Russia. Unlike most other atypical antipsychotics, it shows high in vivo occupancy of dopamine D2 and D3 receptors at clinically relevant doses. In animal models, cariprazine has demonstrated dopamine D3 receptor-dependent pro-cognitive and anti-anhedonic effects, suggesting its potential for treating negative symptoms. This review summarizes the efficacy of cariprazine in the treatment of negative symptoms of schizophrenia. A literature search of databases covering international and Russian journals, for articles published between 1st January 2010 and 1st June 2020. Cariprazine demonstrated at least comparable efficacy in the treatment of schizophrenia symptoms to active comparators including risperidone, olanzapine or aripiprazole. The drug has a good safety profile. It appeared to be associated with a lower risk of metabolic syndromes and most extrapyramidal symptoms. The positive effect of cariprazine on the negative symptoms of schizophrenia may be associated with the elimination of secondary negative symptoms. However, of all the atypical antipsychotics to date, only cariprazine has a convincingly, methodologically robust proven advantage over risperidone in eliminating the predominant negative symptoms of schizophrenia. Yet only four studies have investigated the effect of cariprazine on the negative symptoms of schizophrenia. There is a lack of research into its direct impact on emotional-volitional disorders, anhedonia, cognitive symptoms and personality changes. However, there is evidence to suggest cariprazine is effective in treatment-resistant cases, but this requires further confirmation. Cariprazine is an effective and well-tolerated agent for the treatment of schizophrenia and may be effective in cases where other antipsychotics have failed. Cariprazine has been shown to have a positive effect on negative symptoms. Further studies are needed to collect more data on long-term treatment of schizophrenia and especially negative symptoms.

The preclinical discovery and development of paliperidone for the treatment of schizophrenia

ABSTRACTIntroduction: Paliperidone is approved in the United States and Europe for the short- and long-term treatment of schizophrenia in adults and adolescents as well as for the acute treatment of schizoaffective disorder either as monotherapy or adjunctive therapy to mood stabilizers and/or antidepressants. It is recommended in patients with hepatic impairment and evokes less drug–drug interactions.Areas covered: This review article focuses on the preclinical discovery of paliperidone, the major active metabolite of risperidone. It provides details regarding paliperidone’s pharmacological and neurochemical mechanisms, and their contribution to therapeutic benefits and adverse effects, based on the available literature with respect to the preclinical and clinical findings and product labels.Expert opinion: Paliperidone exhibits a high affinity and antagonistic activity toward D2 and 5-HT2A receptors, followed by 5-HT7, H1, α1, and α2 receptors. In preclinical studies, paliperidone produces antidepressant, anxiolytic, mood-stabilizing, analgesic actions, and affects the endocannabinoid system. It is also known to evoke procognitive, antioxidant, and anti-inflammatory activities. Its positive activity on neurogenesis, neuronal, and synaptic plasticity deserves to be emphasized. The clinical superiority of paliperidone is based primarily on the available formulations of the drug rather than in the subtle differences in its pharmacokinetic/pharmacodynamic properties compared to risperidone.

Paliperidone extended-release in the short- and long-term treatment of schizophrenia.

Paliperidone is a second-generation antipsychotic drug belonging to the class of benzisoxasole derivatives. Paliperidone is the major active metabolite of risperidone (9-OH-risperidone) and, as such, is comparable to the latter in terms of pharmacodynamic properties. However, due to its peculiar characteristics, paliperidone may be particularly useful in the treatment of schizophrenic patients. In this critical review of the literature the efficacy and tolerability in the short- and in the long-term have been evaluated in patients with schizophrenia. Taking into account the tolerability and efficacy data, together with the use of innovative sustained-release formulation, with a peculiar pharmacokinetic profile that allows single daily administration, paliperidone can be considered a valid option both for the short and the long-term treatment of schizophrenia.

Paliperidone palmitate in short- and long-term treatment of schizophrenia.

Poor adherence to treatment remains a major problem in the management of patients with schizophrenia. In the 60s, first generation antipsychotics in depot formulation have been introduced on the market with the aim to improve adherence to therapy. However, the limited effectiveness on negative symptoms and the tendency to induce extrapyramidal side effects has limited their use. Currently there are five second-generation antipsychotic long-acting formulations and the use of these drugs has definitely changed perspective: they are no more restricted as compounds intended to improve compliance, but they can be considered first-line drugs with proven efficacy and good tolerability. In this narrative review the efficacy and tolerability of paliperidone palmitate, as well as the economic impact of the use of this particular molecule, have been evaluated in the short- and long-term treatment of schizophrenia. Taking into account the results of different studies, paliperidone, especially in his long-acting formulation, can be considered a viable and effective treatment for patients with schizophrenia, both in the short- and in the long term.

Cost/effectiveness of aripiprazole vs. olanzapine in the long-term treatment of schizophrenia

Introduction/Objective. Although effectiveness of atypical antipsychotics in patients with schizophrenia is mostly similar, there are significant differences in adverse effects rate and treatment costs, making comparison of their cost/effectiveness ratios essential for optimal drug choice. The aim of this study was to compare cost/effectiveness of aripiprazole and olanzapine in long-term treatment of schizophrenia. Methods. A four-state, three-month cycle Markov model was built to compare aripiprazole and olanzapine. The model assumed that patients who relapse on treatment with both aripiprazole and olanzapine are further treated with clozapine. The perspective of the National Health Insurance Fund was chosen, and the period covered by the model was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Both multiple one-way and probabilistic sensitivity analysis was made. Results. After base-case analysis aripiprazole was dominated by olanzapine, as net monetary benefit was negative (-390,341.96 ?} 29,131.53 RSD) and incremental cost/effectiveness ratio (ICER) was above the willingness-to-pay line of one Serbian gross domestic product per capita per quality-adjusted life year (QALY) gained. Multiple one-way and probabilistic sensitivity analysis confirmed results of the base case simulation. Conclusion. Olanzapine has more beneficial cost/effectiveness ratio than aripiprazole for long-term treatment of schizophrenia in Serbian milieu.

PMH24 - COST IMPLICATIONS OF ANTIPSYCHOTICS DRUGS: A HOSPITAL BUDGET IMPACT MODEL

the primary objective was to create an interactive model to analyze the budget impact of maintenance therapy with different antipsychotics (APs) from the Russian hospital perspective. an interactive, customizable model in Excel was built to calculate the costs and to provide pharmacoeconomic assessment of antipsychotic therapy. Cost-minimization (CMA), cost-effectiveness (CEA) and budget impact analysis (BIA) were used to conduct economic evaluation of standard doses therapy (according to national guidelines) of APs. Data on antipsychotics used in the long-term treatment of schizophrenia were derived from meta-analysis. Mean standard treatment duration was 60 days in inpatients facilities. Costs for drugs were estimated from the national hospitals sources (2015). Exchange rate in the analyzed period was €1 = 71.8 RUB. CMA showed, that clozapine demonstrated the lowest costs per patient (€25) followed by olanzapine (€202) with the assumption that they have similar effectiveness. Olanzapine was associated with higher drug costs relative to haloperidol (€202 vs. €2.3), but also had statistically significantly greater total effectiveness - mean relapse prevention rate was 83% and 72% respectively (OR=0.50, 95% CI 0.30–0.82). The ICER for olanzapine (€1,818) was 15 times less than willingness to pay the threshold for Russia (3-times GDP). The developed evaluation instrument enabled to estimate the budget impact of olanzapine (greater effectiveness) for two identical cohorts (n=200) of patients with schizophrenia: the model predicted a 18.6% increase in net costs for olanzapine in case of increase by 5% its utilization with an alternative haloperidol decreases in the same proportion (with base case proportion 24 and 76% respectively). results suggest that direct inpatients costs on mental healthcare could be minimized by using clozapine instead of olanzapine. In comparison with haloperidol the use of olanzapine in the treatment of schizophrenia is the cost-effective alternative for the Russian National health service.

The effects of brexpiprazole and aripiprazole on body weight as monotherapy in patients with schizophrenia and as adjunctive treatment in patients with major depressive disorder: an analysis of short-term and long-term studies.

The aim of this analysis was to explore the effects of brexpiprazole and aripiprazole on body weight when used as monotherapy to treat schizophrenia and as adjunctive treatment to antidepressant treatment (ADT) for major depressive disorder (MDD) in short-term (4/6 weeks) and long-term (≤52 weeks) studies. Body weight data were obtained from the clinical studies of each drug (brexpiprazole and aripiprazole), in schizophrenia and adjunctive treatment of MDD. Data were pooled and analyzed to assess the mean change in body weight and to determine the incidence of a clinically relevant change in body weight from baseline (≥7% increase or decrease, at any time) in each treatment group. The overall weight profiles for brexpiprazole and aripiprazole in the short-term and long-term treatment of schizophrenia, and MDD (adjunctive to ADT), were similar. In short-term schizophrenia studies, the mean weight increase was 1.2 kg for brexpiprazole and 0.6 kg for aripiprazole. In short-term MDD studies (adjunctive to ADT), the mean weight increase was 1.5 kg for brexpiprazole and 1.6 kg for aripiprazole. In the long-term schizophrenia studies, at week 52, the mean weight increase was 2.1 kg for brexpiprazole and 3.0 kg for aripiprazole. In long-term MDD studies (adjunctive to ADT), at week 52, the mean weight increase was 3.2 kg for brexpiprazole and 4.0 kg for aripiprazole. Clinically relevant increases or decreases in body weight were also similar for brexpiprazole and aripiprazole. Overall, in the treatment of schizophrenia, and in adjunctive treatment of MDD, brexpiprazole and aripiprazole have a similar effect on body weight over the course of 1 year.

Drug-induced toxic hepatitis associated with the combination of quetiapine and fluphenazine: A case report

Toxic hepatitis is an inflammation of the liver that occurs in response to various substances, such as alcohol, drugs and various chemicals. It may develop either within hours or days, or after several months or years of exposure to a toxic agent. Schizophrenia is a chronic and progressive disease with a high risk for the development of various somatic diseases. Previous studies have shown that all generations of antipsychotics can cause a variety of somatic disturbances, visible in laboratory parameters, which can lead to serious physical disorders. Therefore, during long-term treatment with antipsychotics we must pay attention to the impact of drugs on the development of certain physical disturbances. In our case, the long-term treatment of schizophrenia with quetiapine and fluphenazine led to the development of mild toxic hepatitis. Our goal was to pay attention to the risks of prescribing a combination of antipsychotics in order to prevent the development of physical disease in psychiatric patients.

Do antipsychotic drugs lose their efficacy for relapse prevention over time?

There is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis

BackgroundSchizophrenia is a chronic and debilitating neuropsychiatric disorder that often requires long-term pharmacotherapy to manage symptoms and prevent relapse. Cariprazine is a potent dopamine D3 and D2 receptor partial agonist that is FDA-approved in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults; the recommended dose range is 1.5–6 mg/d.MethodsTo further characterize the long-term safety of cariprazine, data from two 48-week open-label, flexible-dose extension studies were pooled for post hoc analyses. Outcomes were evaluated in the pooled safety population (patients who received ≥1 dose of cariprazine during an open-label extension period); findings were summarized using descriptive statistics for the overall cariprazine group and in modal daily dose groups (1.5–3, 4.5–6, and 9 mg/d).ResultsOf the 679 patients in the overall cariprazine safety population, 40.1% completed the study. The only adverse events (AEs) leading to discontinuation of ≥2% of patients in any dose group were akathisia, worsening of schizophrenia, and psychotic disorder. Treatment-emergent AEs (TEAEs) of akathisia, insomnia, weight increased, and headache were reported in ≥10% of the overall population. Mean prolactin levels decreased in all dose groups (overall, −15.4 ng/mL). Clinically insignificant changes in aminotransferase levels and alkaline phosphatase were observed; no dose-response relationship was observed across groups. Mean total (−5.3 mg/dL), low-density lipoprotein (−3.5 mg/dL), and high-density lipoprotein (−0.8 mg/dL) cholesterol levels decreased; no dose-response relationship was observed for metabolic parameters. Mean change in body weight was 1.58 kg; body weight increase and decrease ≥7% occurred in 27% and 11% of patients, respectively. Mean changes in cardiovascular parameters, including blood pressure and pulse, were generally not considered clinically significant. EPS-related TEAEs that occurred in ≥5% of patients were akathisia, tremor, restlessness, and extrapyramidal disorder.ConclusionIn these post hoc pooled analyses of data from 2 long-term open-label studies, treatment with cariprazine was generally safe and well tolerated. Results support the safety and tolerability of cariprazine within the FDA-recommended dose range of 1.5–6 mg/d for schizophrenia.Clinical trials registrationNCT01104792, NCT00839852.

Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study

RationaleCariprazine, a dopamine D3/D2 receptor partial agonist antipsychotic, demonstrated efficacy and tolerability in 6-week, randomized, placebo-controlled schizophrenia trials. Schizophrenia is a chronic disorder that requires continuous treatment; therefore, the long-term safety and tolerability profile of antipsychotic agents is an important factor in guiding clinician decisions.ObjectiveThis single-arm, open-label extension study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia.MethodsPatients enrolled in this study completed a 6-week, randomized, placebo- and active-controlled study and had responded (Clinical Global Impressions-Severity [CGI-S] ≤3; ≥20 % reduction in Positive and Negative Syndrome Scale [PANSS] total score) to treatment at the end of the lead-in study. Patients (N = 93) received flexibly dosed, open-label cariprazine (1.5–4.5 mg/day) for up to 48 weeks.ResultsApproximately 50 % (46/93) of patients completed the 48 weeks of open-label treatment. The most common adverse events (AEs) were akathisia (14 %), insomnia (14 %), and weight increased (12 %). Serious AEs (SAEs) occurred in 13 % of patients; 11 % discontinued due to AEs. Mean changes in metabolic parameters were generally small and not clinically relevant. Mean body weight increased by 1.9 kg from the start of the lead-in study to the end of the extension study. There were no discontinuations associated with change in metabolic parameters or body weight. Long-term cariprazine treatment was not associated with prolactin elevation or clinically significant changes in cardiovascular parameters.ConclusionsIn this 48-week, single-arm trial, open-label cariprazine (1.5–4.5 mg/day) treatment was generally safe and well tolerated with no new safety concerns associated with long-term treatment.

Critical evaluation of paliperidone in the treatment of schizophrenia in Chinese patients: a systematic literature review.

BackgroundPaliperidone (9-hydroxyrisperidone), the major active metabolite of risperidone, has been introduced as a novel atypical antipsychotic agent in many countries. It is available both as an oral extended-release (ER) formulation and as a long-acting injection (paliperidone palmitate, PP), which have been approved for treating schizophrenia in the People’s Republic of China since 2009 and 2012, respectively. This systematic review summarizes the efficacy, effectiveness, and safety of paliperidone in the treatment of schizophrenia in the Chinese population.MethodsA systematic literature search was conducted on the databases covering international and Chinese core journals, published from January 1, 2008, to May 22, 2015.ResultsA total of 122 publications were retrieved, of which 63 studies were identified for inclusion; most studies were related to paliperidone ER (n=53), nine were related to PP, and one study was related to both agents. Paliperidone ER demonstrated at least comparable efficacy with active comparators, including risperidone, olanzapine, ziprasidone, or aripiprazole, and was found to be superior with respect to the onset of action and improvement in the Personal and Social Performance Scale score. Paliperidone ER appeared to be associated with a lower risk of metabolic syndromes; the most common treatment-emergent adverse events were extrapyramidal symptoms, akathisia, insomnia, and somnolence. Results from interventional and observational studies showed that PP was also an effective and well-tolerated treatment for Chinese patients with schizophrenia. The findings were generally consistent with those observed in non-Chinese populations.ConclusionBoth paliperidone ER and PP were effective and well-tolerated agents for the treatment of schizophrenia in the Chinese population according to the data we reviewed. No new safety signals specific for the Chinese population were raised for paliperidone. Further studies may be needed to collect more data on long-term treatment of schizophrenia in the People’s Republic of China.

Lurasidone: a novel antipsychotic agent for the treatment of schizophrenia and bipolar depression.

Lurasidone is a novel antipsychotic agent approved for the treatment of schizophrenia in a number of countries including the UK, and is also approved in the USA and Canada for the treatment of major depressive episodes associated with bipolar I disorder as either a monotherapy or adjunctive therapy with lithium or valproate. In addition to full antagonist activity at dopamine D2 (Ki(D2) = 1 nM) and serotonin 5-HT2A (Ki(5-HT2A) = 0.5 nM) receptors, the pharmacodynamic profile of lurasidone is notable for its high affinity for serotonin 5-HT7 receptors (Ki(5-HT7) = 0.5 nM) and its partial agonist activity at 5-HT1A receptors (Ki(5-HT1A) = 6.4 nM). Long-term treatment of schizophrenia with lurasidone has been shown to reduce the risk of relapse. Lurasidone appears associated with minimal effects on body weight and low risk for clinically meaningful alterations in glucose, lipids or electrocardiogram parameters.

The clinical utility of lurasidone in schizophrenia: patient considerations.

Lurasidone is a novel antipsychotic agent approved for the treatment of schizophrenia in a number of countries including the United Kingdom, other European countries, the United States, and Canada. In addition to full antagonist activity at the dopamine D2 (Ki, 1 nM) and serotonin 5-HT2A (Ki, 0.5 nM) receptors, the pharmacodynamic profile of lurasidone is notable for its high affinity for serotonin 5-HT7 receptors (0.5 nM) and its partial agonist activity at 5-HT1A receptors (Ki, 6.4 nM). Long-term treatment of schizophrenia with lurasidone has been shown to reduce the risk of relapse in patients with schizophrenia. Lurasidone appears to be associated with minimal effects on body weight, and low risk for clinically meaningful alterations in glucose, lipids, or electrocardiography parameters. Evidence from two randomized trials also suggests improvement in functional capacity and cognitive functioning in people with schizophrenia. A significant evidence base supports the use of lurasidone as a promising agent for the treatment of schizophrenia.

P.3.d.025 Safety and tolerability of cariprazine in long-term treatment of schizophrenia: integrated summary of safety data

The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum β-lactamase (ESBL)-producing pathogens, novel β-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs.