György Németh - Academia.edu (original) (raw)

Papers by György Németh

Research paper thumbnail of Clinical Global Impression of Cariprazine in Negative Symptom Schizophrenia Patients: Comparison of clinical trial data vs. real-world evidence

European Psychiatry

IntroductionThere is an increasing need to understand the effectiveness of novel medications in r... more IntroductionThere is an increasing need to understand the effectiveness of novel medications in real-world context since despite being the gold standard, double-blind trials have their own limitations as well. Clinical Global Impression is a simple tool for clinicians to assess the severity of an illness (CGI-Severity) as well as to rate how much the patient’s disorder has improved or worsened relative to baseline (CGI-Improvement). In this poster, cariprazine, a third-generation antipsychotic medication that was found to be effective in the treatment of negative symptoms in schizophrenia will be evaluated.ObjectivesTo compare the effectiveness of cariprazine in clinical trial vs real-world setting via the CGI-S and CGI-I scales in negative symptom schizophrenia patients.MethodsWe compared the results of a clinical trial (Németh et al. Lancet 2017; 389:1103-13) and an observational study (Rancans et al. Int Clin Psychopharmacol. 2021;36(3):154-161). The latter was an open-label, fle...

Research paper thumbnail of Tolerability of cariprazine in the early stage of schizophrenia: A pooled, post-hoc analysis of 4 phase ii/iii double-blind placebo-controlled trials

European Psychiatry, 2021

Introduction In the early stage of schizophrenia (first 5 years), the most important clinical tar... more Introduction In the early stage of schizophrenia (first 5 years), the most important clinical target besides symptom control is relapse prevention as each relapse significantly decreases the possibility of preferable long-term outcomes. Early discontinuation of antipsychotic medication due to intolerable side-effects is one of the most common causes of relapse. Objectives This poster aims to present cariprazine’s tolerability in the early stage of schizophrenia. Methods Data from 4 randomized, double-blind, placebo-controlled trials (NCT00404573, NCT01104766, NCT01104779, NCT00694707) with similar design (1 week of wash out period, 6 weeks of treatment and 2-4 weeks of follow-up) were pooled. For the post-hoc analysis, patients with early stage of schizophrenia (defined as having a disease duration of less than 5 years) were extracted from the whole safety population, and approved doses of cariprazine (1.5-6.0 mg/day) were combined. Treatment-emergent adverse events (TEAEs) and disc...

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

European Psychiatry, 2021

IntroductionMotivation deficit is a significant aspect of lack of improvement in patients with sc... more 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 ...

Research paper thumbnail of Population Pharmacogenomics and Personalized Medicine Research in Hungary: Achievements and Lessons Learned

Current Pharmacogenomics and Personalized Medicine, 2010

There have been a number of notable strides in Hungary in the field of population pharmacogenomic... more There have been a number of notable strides in Hungary in the field of population pharmacogenomics. This paper aims to summarize and share the recent experiences in population genomics and personalized medicine in Hungary with leaders of the Genomic National Technology Platform. The present day Hungary differs from other populations in the region as Hungary was established some 1100 years ago, with founders of the ancestral Hungarian population originating from the east side of the Urals. Additionally, the Roma population of about 700,000 represents the largest ethnic minority living in Hungary. In a series of investigations, we found significant differences between the Hungarian and Roma populations in clinically relevant pharmacogenomics targets such as VKORC1 and CYP2C9 genes. Pharmacogenomics applications are also of interest from the standpoint of biomarker-guided drug discovery in Hungary which we highlight briefly in this paper. Regulatory, ethical and economic aspects of genomics are other dimensions crucial for efficient transition of basic genomics discoveries from laboratory to the clinic. Importantly, Hungary has a Parliamental Act for regulation of genetic diagnostic and research test procedures, and for regulation of biobanks since 2008. Diagnostic molecular pharmacogenomics tests are reimbursed from the same insurance budget as with the other molecular biology based tests in Hungary. Personalized medicine diagnostics require further considerations on how best to integrate and reimburse them in routine healthcare as this new field evolves in Hungary.

Research paper thumbnail of What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial

Frontiers in Psychiatry

IntroductionMinimum clinically important difference (MCID) is a measure that defines the minimum ... more IntroductionMinimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence.MethodsData of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression—Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID1); as the difference between the PANSS...

Research paper thumbnail of Fibromuscular Dysplasia of the Basilar Artery

Archives of neurology, Apr 1, 1984

Seven histologically confirmed cases of intracranial fibromuscular dysplasia (FMD) have been publ... more Seven histologically confirmed cases of intracranial fibromuscular dysplasia (FMD) have been published. A new case of intracranial FMD confined to the basilar artery occurred in a 32-year-old man. The proliferation of fibroblasts and smooth-muscle cells could be observed only in the intima detaching from the media. The neurologic symptoms corresponding to akinetic mutism occurred nine days after pulmonary lobectomy for aspergilloma. We believe that this pure intimal type of FMD consisting of cells without elastic and collagen fibers represents a more undifferentiated and therefore more progressive form of the disease. The FMD can be considered as an overwhelming reaction of so-called pluri-potential smooth-muscle cells of the arterial wall to various stimuli.

Research paper thumbnail of Akinetic mutism and locked-in syndrome: the functional-anatomical basis for their differentiation

PubMed, Apr 1, 1986

The accurate location and extent of brainstem lesions that cause akinetic mutism (a.m.) and/or lo... more The accurate location and extent of brainstem lesions that cause akinetic mutism (a.m.) and/or locked-in syndrome (LiS) are reviewed. We compared the data of our morphological analysis with recent neurochemical findings and speculated on the possible pathomechanism that results in the clinical state. There seems to be an anatomic correspondence between pathways of dopamine containing neurons and the lesions associated with a.m. We argue that mesocoeruleo, diencephalospinal and/or mesocorticolimbic dopaminergic systems are selectively damaged in a.m. but spared in LiS.

Research paper thumbnail of Novel pharmaceutical compositions with increased activity

Research paper thumbnail of Pharmaceutical Composition of a Sodium Channel Blocker and a Selective Serotonin Uptake Inhibitor

Research paper thumbnail of Egy kapszula azonosítása

Research paper thumbnail of Pharmaceutical compositions with increased activity

Research paper thumbnail of Pharmaceutical combination for the treatment of spasticity and/or pain

Research paper thumbnail of Kihívások és hajtóerők az első magyar blockbuster molekula nemzetközi fejlesztési folyamatában

Informatika és menedzsment az egészségügyben, May 4, 2023

Research paper thumbnail of Relationship between diencephalic damages and schizophrenia?

Research paper thumbnail of First-in-class treatment of negative symptoms of schizophrenia

Intrinsic activity, Sep 5, 2016

Research paper thumbnail of Quality-adjusted life year difference in patients with predominant negative symptoms of schizophrenia treated with cariprazine and risperidone

Journal of Comparative Effectiveness Research, Nov 1, 2017

Our study aimed at estimating differences in quality-adjusted life year (QALY) gain for patients ... more Our study aimed at estimating differences in quality-adjusted life year (QALY) gain for patients with predominant negative symptoms of schizophrenia treated with cariprazine compared with risperidone. Materials & methods: A Markov model was built, based on the Mohr-Lenert approach and data derived from clinical trials, to estimate potential QALY gains of patients. Results: Patients had higher probability of reaching better health states treated with cariprazine compared with risperidone. In the model, this resulted in an estimated QALY gain of 0.029 per patient, after 1 year of treatment. Conclusion: Cariprazine, which showed clinically meaningful improvement in the symptoms, and personal and social performance, can also provide significant QALY gain in the treatment of patients with predominant negative symptoms of schizophrenia compared with risperidone.

Research paper thumbnail of From a Pathophysiological Concept to a New Drug

European Psychiatry, Jun 1, 2022

Research paper thumbnail of Cariprazine’s efficacy in treating depressive symptoms – pooled data from schizophrenia, bipolar depression and major depression trials

European Psychiatry

IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar di... more IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar disorder and major depressive disorder (MDD). Their emergence is related to altered neurotransmission at the serotonin receptors and potentially at dopamine D3 receptors.ObjectivesThe aim of this analysis was to examine the efficacy of cariprazine (CAR) in treating depressive symptoms in SCH, bipolar depression (BD) and MDD.MethodsClinical trials with randomised, double-blind, placebo (PLB)-controlled designs were included in these analyses. Data from 3 SCH [NCT00694707, NCT01104766, NCT01104779; 1.5-9 mg/d] and 3 BD [NCT01396447, NCT02670538, NCT02670551; 1.5-3 mg/d] studies were pooled. In MDD, add-on CAR to antidepressant treatment was evaluated against PLB in two studies [NCT03738215: 1.5 and 3 mg/d; NCT01469377: 1-2 mg/d and 2-4.5 mg/d).Least square (LS) mean changes were analysed using Mixed Model Repeated Measures: from baseline (BL) to Week 6 in the Positive and Negative Syndrome S...

Research paper thumbnail of Relationship between diencephalic damages and schizophrenia?

Research paper thumbnail of The adult form of subacute necrotizing encephalopathy

Surgical Neurology, 1984

The rare adult form of subacute necrotizing encephalopathy in a 49-year-old man is reported. Six ... more The rare adult form of subacute necrotizing encephalopathy in a 49-year-old man is reported. Six months before admission the previously healthy and nonalcoholic patient developed progressive hemiparesis of the left side and instability of gait. Ventriculography revealed marked narrowing of the aqueduct, and after ventriculocisternotomy the patient became akinetic and mute. The post-mortem histologic examination revealed pathologic changes characteristic of subacute necrotizing encephalopathy. This case demonstrates that this rare disease in an adult may cause both akinetic mutism and aqueductal stenosis.

Research paper thumbnail of Clinical Global Impression of Cariprazine in Negative Symptom Schizophrenia Patients: Comparison of clinical trial data vs. real-world evidence

European Psychiatry

IntroductionThere is an increasing need to understand the effectiveness of novel medications in r... more IntroductionThere is an increasing need to understand the effectiveness of novel medications in real-world context since despite being the gold standard, double-blind trials have their own limitations as well. Clinical Global Impression is a simple tool for clinicians to assess the severity of an illness (CGI-Severity) as well as to rate how much the patient’s disorder has improved or worsened relative to baseline (CGI-Improvement). In this poster, cariprazine, a third-generation antipsychotic medication that was found to be effective in the treatment of negative symptoms in schizophrenia will be evaluated.ObjectivesTo compare the effectiveness of cariprazine in clinical trial vs real-world setting via the CGI-S and CGI-I scales in negative symptom schizophrenia patients.MethodsWe compared the results of a clinical trial (Németh et al. Lancet 2017; 389:1103-13) and an observational study (Rancans et al. Int Clin Psychopharmacol. 2021;36(3):154-161). The latter was an open-label, fle...

Research paper thumbnail of Tolerability of cariprazine in the early stage of schizophrenia: A pooled, post-hoc analysis of 4 phase ii/iii double-blind placebo-controlled trials

European Psychiatry, 2021

Introduction In the early stage of schizophrenia (first 5 years), the most important clinical tar... more Introduction In the early stage of schizophrenia (first 5 years), the most important clinical target besides symptom control is relapse prevention as each relapse significantly decreases the possibility of preferable long-term outcomes. Early discontinuation of antipsychotic medication due to intolerable side-effects is one of the most common causes of relapse. Objectives This poster aims to present cariprazine’s tolerability in the early stage of schizophrenia. Methods Data from 4 randomized, double-blind, placebo-controlled trials (NCT00404573, NCT01104766, NCT01104779, NCT00694707) with similar design (1 week of wash out period, 6 weeks of treatment and 2-4 weeks of follow-up) were pooled. For the post-hoc analysis, patients with early stage of schizophrenia (defined as having a disease duration of less than 5 years) were extracted from the whole safety population, and approved doses of cariprazine (1.5-6.0 mg/day) were combined. Treatment-emergent adverse events (TEAEs) and disc...

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

European Psychiatry, 2021

IntroductionMotivation deficit is a significant aspect of lack of improvement in patients with sc... more 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 ...

Research paper thumbnail of Population Pharmacogenomics and Personalized Medicine Research in Hungary: Achievements and Lessons Learned

Current Pharmacogenomics and Personalized Medicine, 2010

There have been a number of notable strides in Hungary in the field of population pharmacogenomic... more There have been a number of notable strides in Hungary in the field of population pharmacogenomics. This paper aims to summarize and share the recent experiences in population genomics and personalized medicine in Hungary with leaders of the Genomic National Technology Platform. The present day Hungary differs from other populations in the region as Hungary was established some 1100 years ago, with founders of the ancestral Hungarian population originating from the east side of the Urals. Additionally, the Roma population of about 700,000 represents the largest ethnic minority living in Hungary. In a series of investigations, we found significant differences between the Hungarian and Roma populations in clinically relevant pharmacogenomics targets such as VKORC1 and CYP2C9 genes. Pharmacogenomics applications are also of interest from the standpoint of biomarker-guided drug discovery in Hungary which we highlight briefly in this paper. Regulatory, ethical and economic aspects of genomics are other dimensions crucial for efficient transition of basic genomics discoveries from laboratory to the clinic. Importantly, Hungary has a Parliamental Act for regulation of genetic diagnostic and research test procedures, and for regulation of biobanks since 2008. Diagnostic molecular pharmacogenomics tests are reimbursed from the same insurance budget as with the other molecular biology based tests in Hungary. Personalized medicine diagnostics require further considerations on how best to integrate and reimburse them in routine healthcare as this new field evolves in Hungary.

Research paper thumbnail of What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial

Frontiers in Psychiatry

IntroductionMinimum clinically important difference (MCID) is a measure that defines the minimum ... more IntroductionMinimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence.MethodsData of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression—Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID1); as the difference between the PANSS...

Research paper thumbnail of Fibromuscular Dysplasia of the Basilar Artery

Archives of neurology, Apr 1, 1984

Seven histologically confirmed cases of intracranial fibromuscular dysplasia (FMD) have been publ... more Seven histologically confirmed cases of intracranial fibromuscular dysplasia (FMD) have been published. A new case of intracranial FMD confined to the basilar artery occurred in a 32-year-old man. The proliferation of fibroblasts and smooth-muscle cells could be observed only in the intima detaching from the media. The neurologic symptoms corresponding to akinetic mutism occurred nine days after pulmonary lobectomy for aspergilloma. We believe that this pure intimal type of FMD consisting of cells without elastic and collagen fibers represents a more undifferentiated and therefore more progressive form of the disease. The FMD can be considered as an overwhelming reaction of so-called pluri-potential smooth-muscle cells of the arterial wall to various stimuli.

Research paper thumbnail of Akinetic mutism and locked-in syndrome: the functional-anatomical basis for their differentiation

PubMed, Apr 1, 1986

The accurate location and extent of brainstem lesions that cause akinetic mutism (a.m.) and/or lo... more The accurate location and extent of brainstem lesions that cause akinetic mutism (a.m.) and/or locked-in syndrome (LiS) are reviewed. We compared the data of our morphological analysis with recent neurochemical findings and speculated on the possible pathomechanism that results in the clinical state. There seems to be an anatomic correspondence between pathways of dopamine containing neurons and the lesions associated with a.m. We argue that mesocoeruleo, diencephalospinal and/or mesocorticolimbic dopaminergic systems are selectively damaged in a.m. but spared in LiS.

Research paper thumbnail of Novel pharmaceutical compositions with increased activity

Research paper thumbnail of Pharmaceutical Composition of a Sodium Channel Blocker and a Selective Serotonin Uptake Inhibitor

Research paper thumbnail of Egy kapszula azonosítása

Research paper thumbnail of Pharmaceutical compositions with increased activity

Research paper thumbnail of Pharmaceutical combination for the treatment of spasticity and/or pain

Research paper thumbnail of Kihívások és hajtóerők az első magyar blockbuster molekula nemzetközi fejlesztési folyamatában

Informatika és menedzsment az egészségügyben, May 4, 2023

Research paper thumbnail of Relationship between diencephalic damages and schizophrenia?

Research paper thumbnail of First-in-class treatment of negative symptoms of schizophrenia

Intrinsic activity, Sep 5, 2016

Research paper thumbnail of Quality-adjusted life year difference in patients with predominant negative symptoms of schizophrenia treated with cariprazine and risperidone

Journal of Comparative Effectiveness Research, Nov 1, 2017

Our study aimed at estimating differences in quality-adjusted life year (QALY) gain for patients ... more Our study aimed at estimating differences in quality-adjusted life year (QALY) gain for patients with predominant negative symptoms of schizophrenia treated with cariprazine compared with risperidone. Materials & methods: A Markov model was built, based on the Mohr-Lenert approach and data derived from clinical trials, to estimate potential QALY gains of patients. Results: Patients had higher probability of reaching better health states treated with cariprazine compared with risperidone. In the model, this resulted in an estimated QALY gain of 0.029 per patient, after 1 year of treatment. Conclusion: Cariprazine, which showed clinically meaningful improvement in the symptoms, and personal and social performance, can also provide significant QALY gain in the treatment of patients with predominant negative symptoms of schizophrenia compared with risperidone.

Research paper thumbnail of From a Pathophysiological Concept to a New Drug

European Psychiatry, Jun 1, 2022

Research paper thumbnail of Cariprazine’s efficacy in treating depressive symptoms – pooled data from schizophrenia, bipolar depression and major depression trials

European Psychiatry

IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar di... more IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar disorder and major depressive disorder (MDD). Their emergence is related to altered neurotransmission at the serotonin receptors and potentially at dopamine D3 receptors.ObjectivesThe aim of this analysis was to examine the efficacy of cariprazine (CAR) in treating depressive symptoms in SCH, bipolar depression (BD) and MDD.MethodsClinical trials with randomised, double-blind, placebo (PLB)-controlled designs were included in these analyses. Data from 3 SCH [NCT00694707, NCT01104766, NCT01104779; 1.5-9 mg/d] and 3 BD [NCT01396447, NCT02670538, NCT02670551; 1.5-3 mg/d] studies were pooled. In MDD, add-on CAR to antidepressant treatment was evaluated against PLB in two studies [NCT03738215: 1.5 and 3 mg/d; NCT01469377: 1-2 mg/d and 2-4.5 mg/d).Least square (LS) mean changes were analysed using Mixed Model Repeated Measures: from baseline (BL) to Week 6 in the Positive and Negative Syndrome S...

Research paper thumbnail of Relationship between diencephalic damages and schizophrenia?

Research paper thumbnail of The adult form of subacute necrotizing encephalopathy

Surgical Neurology, 1984

The rare adult form of subacute necrotizing encephalopathy in a 49-year-old man is reported. Six ... more The rare adult form of subacute necrotizing encephalopathy in a 49-year-old man is reported. Six months before admission the previously healthy and nonalcoholic patient developed progressive hemiparesis of the left side and instability of gait. Ventriculography revealed marked narrowing of the aqueduct, and after ventriculocisternotomy the patient became akinetic and mute. The post-mortem histologic examination revealed pathologic changes characteristic of subacute necrotizing encephalopathy. This case demonstrates that this rare disease in an adult may cause both akinetic mutism and aqueductal stenosis.