Effects Of Cariprazine Research Articles

Symptomatic Profile of Cariprazine in the Context of ICD-11 Domains for Schizophrenia: Review of Clinically Oriented Studies: Симптоматический профиль карипразина в контексте доменов шизофрении в МКБ -11: обзор клинически ориентированных исследований.

One of the innovations in the ICD-11grouping "Schizophrenia and Other Primary Psychotic Disorders" is the implementation of six symptom domains intended to improve diagnostics and treatment of these mental conditions in clinical practice. In this respect, evaluation of the effects of various psychotropic drugs, primarily antipsychotic agents, on the specified psychotic symptom domains is a critical task. The antipsychotic agent cariprazine, registered in many countries worldwide (including Russia) for schizophrenia treatment, was selected as the psychotropic drug model for the purposes of the present review. For the purposes of this review the MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed databases were searched for randomized controlled trials comparing cariprazine with a placebo, or a placebo and one or several antipsychotic agents, and that was performed within the period from January 2014 to March 2021. Cariprazine has proved its efficiency in relation to all symptom groups of the ICD-11 domain "Positive Symptoms", and may be considered a front-line therapy for treatment of the first and multiple episodes of schizophrenia, disorganized thinking, and behavioral disorders in the form of aggressiveness and hostility. Cariprazine has the best evidential base for treatment of various symptoms within the ICD-11 domain "Negative Symptoms" among all antipsychotic agents. The data with regard to the effects of cariprazine on the domain "Depressive Mood Symptoms" are controversial. No data concerning the effects of cariprazine on the domain "Manic Mood Symptoms" are available, but the effectiveness of cariprazine monotherapy for manic episodes without any psychomotor agitation signs in the instance of bipolar disorder has been demonstrated. The effectiveness of cariprazine therapy for the ICD-11 domain "Psychomotor Symptoms" has not been investigated, either within the framework of monotherapy or in the course of adjuvant therapy. The effectiveness of cariprazine has been demonstrated in treatment of the domain "Cognitive Symptoms", and the pro-cognitive effect of the drug has developed regardless of its impact on any other schizophrenia symptoms. The drug's capability to improve the functioning of patients with schizophrenia was demonstrated regardless of the impact on psychotic symptoms. Cariprazine is the first-line drug for treatment of the domain "Negative Symptoms" as well as representing front-line therapy for the treatment of ICD-11 domains "Positive Symptoms" and "Cognitive Symptoms". Additional studies will be required in order to evaluate the effects of cariprazine on the ICD-11 domains "Manic Mood Symptoms" and "Depressive Mood Symptoms".

Effect of cariprazine on quality of life and attention in patients with persistent negative symptoms of schizophrenia – a post-hoc analysis

Effect of cariprazine on quality of life and attention in patients with persistent negative symptoms of schizophrenia – a post-hoc analysis

P.0904 Results of a phase 1 trial investigating the effect of cariprazine on the pharmacokinetics of a combined oral contraceptive

P.0904 Results of a phase 1 trial investigating the effect of cariprazine on the pharmacokinetics of a combined oral contraceptive

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder

RationaleAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted.ObjectivesThe aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD.MethodsTo induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment.ResultsCariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine.ConclusionsIn the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

The effect of cariprazine on patient engagement: Post-hoc analysis of a phase 3 study in patients with predominant negative symptoms of schizophrenia

IntroductionMotivation deficit is a significant aspect of lack of improvement in patients with schizophrenia especially with predominant negative symptoms (PNS). Therefore, improvement depends not only on symptoms reduction and better social functioning but also on patient engagement which is a key but less investigated aspect of successful treatment.ObjectivesTo investigate and compare patient engagement in PNS patients after cariprazine and risperidone treatment characterized by the 11 items of the Positive and Negative Syndrome Scale (PANSS-11).MethodsIn this phase 3 study patients suffering from PNS of schizophrenia (PANSS-FSNS≥24) were randomized to 26 weeks of treatment with either cariprazine or risperidone (target dose 4.5 and 4 mg/day, respectively). To compare the effects of the two drugs on patient engagement the PANSS-11 scale was used. Change from baseline (CfB) on the selected items and PANSS-11 total score were analyzed using mixed model of repeated measures approach without correction for multiplicity.ResultsPANSS-11 total score mean CfB were -11.20 (SD=0.43) for cariprazine-, and -9.44 (SD=0.45) for risperidone-treated patients with a -1.79 (95% CI=-3.01, -0.56) mean difference (p=0.004) in favor of cariprazine. Most item differences were statistically significant (N1, N2, N3, N4, N5, G16) or numerically higher (N6, G7, G13) for cariprazine versus risperidone.ConclusionsCariprazine significantly improved patient engagement in patients with PNS of schizophrenia compared to risperidone based on the PANSS-11 post-hoc analysis. These results suggest that cariprazine treatment may improve not only the symptoms and everyday functioning of PNS patients but their engagement with life.Conflict of interestStudies were funded by Gedeon Richter Plc. and Allergan Plc (prior to its acquisition by AbbVie). Dr. Laszlovszky, Dombi, Balogh, Dr Barabassy, Dr Vass, Dr. Szatmári and Dr. Németh are employees of Gedeon Richter Plc.

The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task

RationaleAttentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia. We sought to test the ability of partial dopamine D2/D3 agonists, cariprazine and aripiprazole, to attenuate PCP-induced deficits in attentional performance.ObjectivesThe objective of this study is to determine whether systemic administration of cariprazine or aripiprazole attenuated 5-choice serial reaction time task (5-CSRTT) deficits induced by repeated exposure to PCP.MethodsWe utilized a repeated PCP-treatment regimen (2 mg/kg, subcutaneous [s.c.], once daily for 5 days) in rats to induce deficits in the 5-CSRTT. Rats were pre-treated with cariprazine (0.03, 0.1, or 0.3 mg/kg, oral [p.o.]) or aripiprazole (1, 3, or 10 mg/kg, p.o.) to determine whether they prevented PCP-induced deficits in the 5-CSRTT performance.ResultsPCP treatment increased inappropriate responding in the 5-CSRTT, elevating incorrect, premature, and timeout responses. Cariprazine treatment reduced PCP-induced increases in inappropriate responding. However, at higher doses, cariprazine produced non-specific response suppression, confounding interpretation of the attenuated PCP-induced deficits. Aripiprazole treatment also attenuated PCP-induced deficits; however, unlike cariprazine treatment, aripiprazole reduced correct responding and increased omissions.ConclusionsCariprazine and aripiprazole both demonstrated potential in attenuating PCP-induced deficits in the 5-CSRTT performance. While both compounds produced non-specific response suppression, these effects were absent when 0.03 mg/kg cariprazine was administered.

P 90 Novel therapeutic option in the treatment of schizophrenia and bipolar disorder – cariprazine, a partial D2 and D3 receptor agonist

Introduction Schizophrenia and bipolar disorder are generally treated by second-generation antipsychotic drugs. Although they better treat negative schizophrenic symptoms and they exert less often extrapyramidal side effects than first-generation antipschotic drugs, cardiac and metabolic adverse effects weaken their therapeutic effect. Cariprazine, a partial agonist at D2 and D3 receptors, was approved for the treatment of these diseases in September 2015. A question arises, whether this new antipsychotic drug has a sufficient therapeutic effect and few adverse effects. Material/methods Cariprazine is a second-generation antipsychotic drug with a partial agonistic effect at D2 and D3 receptors with a greater affinity for the D3 receptor. In animal experiments, it shows antipsychotic and antimanic effects. Cariprazine has two major metabolites, has a rapid absorption and has a mean half-time of 2–5 days. The most frequent adverse effects are insomnia, extrapyramidal disorders, akathisia, sedation, nausea, dizziness and constipation. Results Cariprazine has been examined in randomized, clinical studies in a phase II. The improvement of positive and negative schizophrenic symptoms was greater than that of placebo. In a clinical study, its effect in the treatment of schizophrenia was compared to that of risperidone. The therapeutic effect of cariprazine was comparable to that of risperidone, although the improvement of positive and negative schizophrenic symptoms was greater in the risperidone group. In a clinical study with patients suffering from bipolar disorder, cariprazine improved the manic symptoms after three weeks better than placebo. Adverse effects occurred in 70% of patients, above all extrapyramidal symptoms such as akathisia and tremor. Extrapyramidal side effects occurred less often than in the risperidone group. Cariprazine shows a favorable metabolic profile, i.e. it increases blood sugar and cholesterol levels to a lesser extent than other antipsychotic drugs. It is a prolactin-sparing antipsychotic drug. Conclusion Cariprazine can be used for the treatment of schizophrenia and bipolar disorder. In clinical studies, its effect is comparable to that of risperidone for the treatment of schizophrenia. Besides, it shows antimanic effects. The most frequent adverse effect is akathisia. It has a favorable metabolic profile and does not raise prolactin levels.

667. The in Vivo Electrophysiological Effects of Cariprazine on the Rat Midbrain Dopaminergic System

667. The in Vivo Electrophysiological Effects of Cariprazine on the Rat Midbrain Dopaminergic System

17. Effects of Cariprazine on Negative Symptoms, Cognitive Impairment, and Prosocial Functioning in Patients With Predominant Negative Symptoms: Post Hoc Analysis of a Phase III, Placebo-, and Active-Controlled Study

Abstract Background: Negative symptoms and cognitive deficits are core symptoms of schizophrenia that have proven to be difficult to treat and are associated with poor social/vocational functioning. Cariprazine (CAR), a D3/D2 receptor partial agonist, is approved in the United States for the treatment of schizophrenia in adults. This post hoc analysis of a Phase 3, randomized, double-blind, placebo- and active-controlled CAR study in adults with acute exacerbation of schizophrenia evaluated the effects of CAR on positive, negative, cognitive, and prosocial functioning domains in a subset of patients with predominant negative symptoms (PNS). Methods: Randomized patients received 6 weeks of double-blind treatment with CAR 3 mg/d, CAR 6 mg/d, aripiprazole 10 mg/d (ARI), or placebo (PBO). For post hoc analyses, patients with PNS were identified using baseline Positive and Negative Syndrome Scale factor scores (PANSS-FS) for positive symptoms (score ≤19; mild to moderate), negative symptoms (score ≥24; moderate to severe), and cognitive impairment (score ≥27; severe). Efficacy parameters included change from baseline to Week 6 in PANSS total score and PANSS-FS for negative, cognitive, and prosocial domains. Results: In all, 131 of 604 randomized patients met criteria for PNS (placebo = 35; CAR 3 mg/d = 27; CAR 6 mg/d = 34; ARI = 35). For CAR 6 mg/d, least squares mean differences (LSMDs) of change from baseline to Week 6 versus placebo were statistically significant on the PANSS total score (-13.9, P = .0132), and negative (-3.3, P = .0112), cognitive (-1.6, P = .0092), and prosocial (-2.9, P = .0035) factor scores. For CAR 3 mg/d, LSMDs versus placebo at Week 6 were statistically significant on the PANSS total score (-14.0; P = .0156), and cognitive (-1.5, P = .0164) and prosocial (-2.5, P = .0187) factor scores. For the negative symptoms factor score, numerical improvement was seen for CAR 3 mg/d over placebo, but the LSMD was not statistically significant at Week 6 (-2.6, P = .0515). In contrast, LSMDs for aripiprazole versus placebo were not statistically significant on PANSS total score (-9.6, P = .0800), negative (-0.6, P = .6449), cognitive (-0.6, P = .3108), or prosocial factor scores (-1.1, P = .2482). In addition, on PANSS-FS for negative symptoms, the LSMD between CAR 6 mg/d and ARI met statistical significance (-2.8, P = .0315). Conclusion: Cariprazine significantly improved overall schizophrenia symptoms, as well as negative, cognitive, and prosocial function versus placebo, in a subset of patients with PNS. These results suggest that cariprazine may be an effective treatment option for the negative symptoms of schizophrenia and its associated domains. Limitations of this analysis include the short duration (6 weeks) for evaluation of negative symptom improvement and the potential that improvements in at least some of the negative symptoms may have been secondary to improvements in positive symptoms.