Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies

Marder, Stephen R.; Fleischhacker, W. Wolfgang; Earley, Willie; Lu, Kaifeng; Zhong, Yan; Németh, György; Laszlovszky, István; Szalai, Erzsébet; Durgam, Suresh

doi:10.1016/j.euroneuro.2018.10.008

Cited by 40 publications

(36 citation statements)

References 51 publications

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“…The overall efficacy of cariprazine in the acute phase of schizophrenia has been demonstrated in pivotal trials and in the subsequent meta-analysis [39][40][41][42]. Using PANSS individual items and PANSS derived factors from pivotal studies results, a post hoc analysis examined the effect of cariprazine in negative symptoms and confirmed the results reported by Nemeth et al [37].…”

Section: Cariprazine Activity From Clinical Trials To Practicementioning

confidence: 56%

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Cariprazine in the Management of Negative Symptoms of Schizophrenia: State of the art and Future Perspectives

et al. 2020

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In schizophrenia, dopaminergic hyperactivity in the mesolimbic regions, or possibly even selectively so in the dorsal striatum, seems to cause the emergence of psychotic symptoms, whereas dopaminergic hypoactivity in cortical regions underlies the negative symptoms and cognitive deficits. Managing the negative symptoms is a major current challenge in the treatment of schizophrenia with a dearth of novel modalities to address this clinical issue. Cariprazine is a novel second-generation antipsychotic that specifically targets the D3 receptor mainly associated to negative symptoms. The review summarizes the main issues regarding negative symptom management and the role of cariprazine treatment.

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Section: Cariprazine Activity From Clinical Trials To Practicementioning

confidence: 56%

“…**p < 0.01; ***p < 0.001. ES: Effect size; LS: Least squares; LSMD: LS mean difference.This image has been reproduced from a paper previously published under the CC-BY-NC-ND license[39].…”

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confidence: 99%

Cariprazine in the Management of Negative Symptoms of Schizophrenia: State of the art and Future Perspectives

et al. 2020

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“…В едином диапазоне зарегистрованных дозировок препарат обеспечивает более высокую относительно препаратов 2-го поколения (рисперидон) [72][73][74][75] эффективность в купировании негативных симптомов и когнитивных расстройств, умеренную эффективность при купировании позитивных симптомов, хотя если рассматривать суммарную эффективность в отношении всех перечисленных симптомов, то в целом она получается более высокой. Важно отметить, что карипразин обнаруживает способность редуцировать психопатологическую симптоматику при минимальном уровне экстрапирамидных расстройств [76,77].…”

Section: Fig 1 Simultaneously Progressive Course Of Positive/negatiunclassified

Negative and positive disorders of schizophrenia (issues of co-dependence, psychopathology and pathogenesis)

Smulevich

Kluschnik

Lobanova

et al. 2020

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Резюме В статье рассматриваются история, современные и собственные представления авторов о связи лежащих в основе шизофрении патологических процессов, реализующихся негативными и позитивными расстройствами. Показано, что по мере развития научной психиатрии модус оценки соотношения позитивных и негативных симптомов кардинально изменялся: от выступающих в клиническом единстве рядоположенных психопатологических образований до гетерогенных по клинико-патогенетической значимости дименсиональных структур. Сделан вывод, что позитивные и негативные расстройства выступают в клиническом пространстве шизофрении в качестве двух психопатологически и патогенетически самостоятельных образований. Считают, что новая парадигма взаимосвязи позитивных и негативных расстройств: взаимодействие позитивных и дефицитарных образований, осуществляемое в клиническом пространстве шизофрении, выявляет дифференцированные для каждой из дименсиональных структур психопатологические функции. Негативные расстройства выступают в качестве «трансформеров», видоизменяющих характеристики первоначально транснозологических позитивных расстройств до уровня предпочтительных для шизофрении психопатологических образований; позитивные симптомокомплексы в свою очередь обнаруживают свойства «модераторов», усиливающих, амплифицирующих проявления дефицитарных дименсий. Представленный в настоящем исследовании психопатологический конструкт связи дименсиональных структур создает условия для разработки новой концепции психофармакотерапии шизофренического дефицита: в качестве «целевых симптомов» медикаментозного воздействия рассматриваются совместно как негативные, так и амплифицирующие их позитивные расстройства.

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“…The notion that, in some individuals, the pathophysiology of schizophrenia can involve systems other than the dopaminergic system supports the argument that schizophrenia is a syndrome of disorders (Jablensky, 2006) and it therefore follows that drug responsiveness could be restricted to specific subgroups within this broad syndrome. In addition, schizophrenia has been suggested to have a number of symptom domains and that responsiveness to drugs may be a function of the specific symptom domain being targeted (Marder et al, 2019). Thus, given the importance of CHRM1 in cognition, it has been postulated that drugs that activate that receptor could be useful in alleviating the cognitive deficits associated with schizophrenia that have proven resistant to treatment with existing antipsychotic drugs (Hopper et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Widespread Changes in Positive Allosteric Modulation of the Muscarinic M1 Receptor in Some Participants With Schizophrenia

Hopper

Pavey

Gogos

et al. 2019

International Journal of Neuropsychopharmacology

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Background Preclinical and some human data suggest allosteric modulation of the muscarinic M1 receptor (CHRM1) is a promising approach for the treatment of schizophrenia. However, it is suggested there is a subgroup of participants with schizophrenia who have profound loss of cortical CHRM1 (MRDS). This raises the possibility that some participants with schizophrenia may not respond optimally to CHRM1 allosteric modulation. Here we describe a novel methodology to measure positive allosteric modulation of CHRM1 in human CNS and the measurement of that response in the cortex, hippocampus, and striatum from participants with MRDS, non-MRDS and controls. Methods The cortex (Brodmann’s area 6), hippocampus, and striatum from 40 participants with schizophrenia (20 MRDS and 20 non-MRDS) and 20 controls were used to measure benzyl quinolone carboxylic acid-mediated shift in acetylcholine displacement of [3H]N-methylscopolamine using a novel in situ radioligand binding with autoradiography methodology. Results Compared with controls, participants with schizophrenia had lower levels of specific [3H]N-methylscopolamine binding in all CNS regions, whilst benzyl quinolone carboxylic acid-modulated binding was less in the striatum, Brodmann’s area 6, dentate gyrus, and subiculum. When divided by subgroup, only in MRDS was there lower specific [3H]N-methylscopolamine binding and less benzyl quinolone carboxylic acid-modulated binding in all cortical and subcortical regions studied. Conclusions In a subgroup of participants with schizophrenia, there is a widespread decreased responsiveness to a positive allosteric modulator at the CHRM1. This finding may have ramifications it positive allosteric modulators of the CHRM1 are used in clinical trials to treat schizophrenia as some participants may not have an optimal response.

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Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies

Cited by 40 publications

References 51 publications

Cariprazine in the Management of Negative Symptoms of Schizophrenia: State of the art and Future Perspectives

Cariprazine in the Management of Negative Symptoms of Schizophrenia: State of the art and Future Perspectives

Negative and positive disorders of schizophrenia (issues of co-dependence, psychopathology and pathogenesis)

Widespread Changes in Positive Allosteric Modulation of the Muscarinic M1 Receptor in Some Participants With Schizophrenia

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