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The effectiveness and safety of cariprazine in schizophrenia patients with negative symptoms and insufficient effectiveness of previous antipsychotic therapy: an observational study.

ABSTRACT: The aim of the study was to examine the effectiveness and safety of cariprazine in routine psychiatric settings on schizophrenia patients with negative symptoms who have been treated with antipsychotics previously but without sufficient success. This was an open-label, flexible-dose, 16-week, observational study in Latvia. The primary outcome measure was an array of anamnesis-based clinical questions on schizophrenia symptoms rated on a seven-point scale. Other outcome measurements were the clinical global impression improvement (CGI-I) and severity (CGI-S) scales. Safety parameters included spontaneous reports of adverse events and specific assessments of extrapyramidal side-effects. A mixed model for repeated measures was fit to the data to evaluate the mean change from baseline for all visits. A total of 116 patients enrolled in the study (completion: 83%). Change from baseline to termination in symptom control was statistically significant (-7.3; P < 0.001), with the most improvement in negative symptoms (-6.3; P < 0.001). Over 70% of patients improved minimally or much based on the CGI-I scores at the final visit, and the CGI-S scores indicated an overall improvement in severity from moderately to mildly ill. 40% of patients experienced treatment-emergent adverse events. Over 70% of doctors were satisfied with the effectiveness and tolerability of cariprazine. Cariprazine significantly improved negative symptoms in schizophrenia patients.

SUBMITTER: Rancans E

PROVIDER: S-EPMC8011502 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Schizophrenia is characterized by positive, negative, cognitive, and affective symptoms. Antipsychotic medications, which work by blocking the dopamine D2 receptor, are the foundation of pharmacotherapy for schizophrenia to control positive symptoms. Cariprazine is a dopamine D3 receptor-preferring D3/D2 partial agonist antipsychotic that is approved for the treatment of schizophrenia (USA and European Union [EU]) and manic and depressive episodes associated with bipolar I disorder (USA). Partial agonist agents have a lower intrinsic activity at receptors than full agonists, so they act as either functional agonists or functional antagonists depending on the surrounding neurotransmitter environment. Beyond efficacy against positive symptoms, the unique D3-preferring partial agonist pharmacology of cariprazine suggests potential advantages against negative symptoms, and cognitive and functional impairment, which are challenging to treat. The efficacy and safety of cariprazine in adult patients with schizophrenia have been demonstrated in four short-term randomized, double-blind, placebo-controlled clinical trials, two long-term open-label studies, one relapse prevention study, and one prospective negative symptom study versus the active comparator risperidone. Additional post hoc investigations have supported efficacy across individual symptoms and domains in schizophrenia, as well as in diverse areas of interest including cognition, functioning, negative symptoms, hostility, and global well-being. This comprehensive review of cariprazine summarizes its pharmacologic profile, clinical trial evidence, and post hoc investigations. Collective evidence suggests that the pharmacology of cariprazine may offer broad-spectrum efficacy advantages for patients with schizophrenia, including effects against difficult-to-treat negative and cognitive symptoms, as well as functional improvements. Cariprazine was generally safe and well tolerated in patients with short- and long-term exposure and no new safety concerns were associated with longer-duration treatment.Trial registration ClinicalTrials.gov identifiers, NCT00404573, NCT00694707, NCT01104766, NCT01104779, NCT01412060, NCT00839852, NCT01104792.

Project description:In clinical practice, clinicians often need to switch antipsychotic medications in patients with schizophrenia to optimize treatment outcomes. Here, we describe the safety and tolerability of switching existing antipsychotic treatments to asenapine or olanzapine monotherapy using various switching regimens.Data were pooled from 949 patients in two 26-week randomized double-blind studies. Patients with persistent negative symptoms of schizophrenia, stable for at least 5 months prior to screening and 1 additional month before randomization, were randomized to and treated with either asenapine (n = 485) or olanzapine (n = 464), and were tapered off existing antipsychotic(s) at variable rates within 28 days.Prior to randomization, most patients were treated with second-generation antipsychotics (SGAs) (asenapine: 79.6%; olanzapine: 78.2%) and first-generation antipsychotics (FGAs) (31.1%; 29.7%), while depot formulations were used by 12.4% and 11.4%, respectively. Median time to taper off previous antipsychotics was 7 days, with approximately 40% of patients abruptly discontinuing their previous medication. Similar percentages of patients in each group reported at least one adverse event (AE) (asenapine: 76.9%; olanzapine: 75.2%). The majority of AEs occurred within the first 28 days. The most frequently reported AEs were somnolence, insomnia, and headache. The incidence of AEs in patients switching from SGAs, FGAs, or depot medications was similar between asenapine and olanzapine (77.5% vs 74.6%, 75.5% vs 79.7%, 85.0% vs 86.8%, respectively). AEs were more frequent in subjects previously treated with two antipsychotics (asenapine: 79.4%; olanzapine: 83.9%) versus one antipsychotic (asenapine: 76.3%; olanzapine: 72.2%) in the switch period.The presented data from post hoc pooled analyses may provide practical guidance for physicians switching partially stabilized patients with schizophrenia and persistent negative symptoms to asenapine or olanzapine.

Project description:BackgroundAtypical antipsychotics as first-line drugs have been used in patients with schizophrenia in China and abroad. However, its safety still needs to be evaluated in a large population, especially in Chinese patients.ObjectiveThe main objective of this study is to evaluate the safety and related factors of long-term atypical antipsychotic use in patients with schizophrenia in China. The secondary objective includes the long-term efficacy of atypical antipsychotics in these patients, as well as pharmacoeconomic evaluation, population pharmacokinetic studies and pharmacogenomics studies.MethodsThis study has an observational design. The atypical antipsychotics include quetiapine, olanzapine, risperidone, aripiprazole, ziprasidone, paliperidone, amisulpride, perospirone and clozapine. Visits occur at 0, 4, 8, 13, 26, 52, 78, 104, 130 and 156 weeks. The efficacy evaluations include symptoms, social function, recurrence rate and hospitalisation. The safety measures include physical examination, vital signs, abdominal circumference, laboratory tests (such as blood cell analysis, blood biochemical tests and serum prolactin/thyroxine levels), 12-lead ECG, extrapyramidal syndrome assessment, sexual function evaluation, medication and other adverse events. The secondary measures include the Positive and Negative Syndrome Scale, Clinical Global Impression-Severity of Illness Scale, Calgary Depression Scale for Schizophrenia, Personal and Social Performance Scale, relapse rate, drug consolidation, medical-related expenses, income, drug plasma concentration and genetic information.ResultsThis is a large sample, non-interventional and long-term prospective clinical study designed to truly reflect the specific details of clinical practice, fully respect patients' needs, and understand patients' treatment intentions and actual treatment details.ConclusionsThis research method details the aims, methods, study design, strengths and limitations of the study.

Project description:ImportanceNegative symptoms are associated with a range of poor clinical outcomes, and currently available treatments generally do not produce a clinically meaningful response. Limited treatment progress may be owing in part to poor clarity regarding latent structure. Prior studies have inferred latent structure using exploratory factor analysis, which has led to the conclusion that there are 2 dimensions reflecting motivation and pleasure (MAP) and diminished expressivity (EXP) factors. However, whether these conclusions are statistically justified remains unclear because exploratory factor analysis does not test latent structure. Confirmatory factor analysis (CFA) is needed to test competing models regarding the latent structure of a construct.ObjectiveTo evaluate the fit of 4 models of the latent structure of negative symptoms in schizophrenia using CFA.Design, setting, and participantsThree cross-sectional studies were conducted on outpatients with schizophrenia who were rated on the 3 most conceptually contemporary measures: Scale for the Assessment of Negative Symptoms (SANS), Brief Negative Symptom Scale (BNSS), and Clinical Assessment Interview for Negative Symptoms (CAINS). Confirmatory factor analysis evaluated the following 4 models: (1) a 1-factor model; (2) a 2-factor model with EXP and MAP factors; (3) a 5-factor model with separate factors for the 5 domains of the National Institute of Mental Health consensus development conference (blunted affect, alogia, anhedonia, avolition, and asociality); and (4) a hierarchical model with 2 second-order factors reflecting EXP and MAP and 5 first-order factors reflecting the 5 consensus domains.Main outcomes and measuresOutcomes included CFA model fit statistics derived from symptom severity scores on the SANS, BNSS, and CAINS.ResultsThe study population included 860 outpatients with schizophrenia (68.0% male; mean [SD] age, 43.0 [11.4] years). Confirmatory factor analysis was conducted on each scale, including 268 patients for the SANS, 192 for the BNSS, and 400 for the CAINS. The 1- and 2-factor models provided poor fit for the SANS, BNSS, and CAINS as indicated by comparative fit indexes (CFIs) and Tucker Lewis indexes (TLIs) less than 0.950, RMSEAs that exceeded the 0.080 threshold, and WRMRs greater than 1.00. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model being more parsimonious. The CFIs and TLIs met the 0.95 threshold and the 1.00 threshold for both factor models with all 3 measures. Interestingly, the RMSEAs for the 5-factor model and the hierarchical model fell under the 0.08 threshold for the BNSS and the CAINS but not the SANS.Conclusions and relevanceThese findings suggest that the recent trend toward conceptualizing the latent structure of negative symptoms as 2 distinct dimensions does not adequately capture the complexity of the construct. The latent structure of negative symptoms is best conceptualized in relation to the 5 consensus domains. Implications for identifying pathophysiological mechanisms and targeted treatments are discussed.

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The effectiveness and safety of cariprazine in schizophrenia patients with negative symptoms and insufficient effectiveness of previous antipsychotic therapy: an observational study.

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