Emerging Treatments in Schizophrenia

Correll, Christoph U.; Abi‐Dargham, Anissa; Howes, Oliver

doi:10.4088/jcp.su21204ip1

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…These safety and tolerability problems have evolved as newer, so-called atypical antipsychotics have become available, but the fundamental problem of AEs related to DA receptor antagonism continues to be a major challenge in the treatment of patients with schizophrenia 4 – 9 . This situation may be changing, with several investigational treatments for schizophrenia currently under development that are devoid of any direct affinity for DA D 2 receptors 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

Correll

Angelov²,

Miller³

et al. 2022

Schizophr

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KarXT combines xanomeline, an M1/M4 preferring muscarinic agonist with no direct D2 receptor antagonism, with the peripherally restricted anticholinergic trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, placebo-controlled, phase 2 study in inpatients with schizophrenia, KarXT met the primary efficacy endpoint, numerous secondary endpoints, and was generally well tolerated. Here, we conducted additional post hoc analyses of safety and tolerability data of KarXT from EMERGENT-1 with a particular focus on adverse events (AEs) that may be associated with muscarinic receptor agonism (nausea or vomiting) or antagonism (dry mouth or constipation). A total of 179 patients received at least one dose of either KarXT (n = 89) or placebo (n = 90) and were included in the analyses. KarXT was associated with a low overall AE burden. The majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred in the first 1−2 weeks of treatment, and were transient with a median duration ranging from 1 day for vomiting to 13 days for dry mouth. No patients in either treatment group discontinued the study due to any procholinergic or anticholinergic AEs. Incidence of somnolence/sedation AEs with KarXT were low and similar to those in the placebo group. KarXT was associated with no significant or clinically relevant changes in body weight, metabolic parameters, or vital signs. KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.

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Section: Introductionmentioning

confidence: 99%

Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

Correll

Angelov²,

Miller³

et al. 2022

Schizophr

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“…35 Although the exact mechanism of action of pimavanserin is unknown, a combination of inverse agonist and antagonist activity at the serotonin 2A (5-HT 2A ) receptors and, to a lesser extent, at the 5-HT 2C receptors, is reported. 36 A recent 26-week phase 2 RCT conducted in patients with predominant negative symptoms of schizophrenia showed a reduction in Treating negative symptoms of schizophrenia negative symptoms after treatment with pimavanserin, although the effect size was small (s.m.d. = −0.21).…”

Section: Treatment Of Negative Symptomsmentioning

confidence: 99%

Treating negative symptoms of schizophrenia: current approaches and future perspectives

2023

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“…Cuando una definición necesita de tantas palabras, lo habitual es que encubra mucho desconocimiento: »La esquizofrenia es una enfermedad multifactorial, implicando a factores genéticos y ambientales, así como alteraciones en el desarrollo cerebral, en su cableado y sincronización. Estas anomalías ocurren en niveles estructurarles, funcionales y moleculares y producen amplios efectos sobre el funcionamiento cognitivo» 1 .…”

Section: El Enigma De La Esquizofreniaunclassified

Tratamiento farmacológico de la esquizofrenia y la esquizofrenia refractaria

Uriarte¹

2022

KRANION

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La comprensión de la esquizofrenia y la efectividad de su tratamiento farmacológico no han experimentado grandes avances en los últimos años, más bien en las últimas décadas. La respuesta al tratamiento es, en muchos casos, incompleta y la presencia de síntomas persistentes y sus consecuencias para la vida laboral, familiar y social de los pacientes pueden ser devastadoras. La clozapina sigue siendo el tratamiento de elección para los pacientes que no responden de manera suficiente a los antipsicóticos habituales, pero tiene limitaciones: no todos los pacientes la toleran, aceptan o incluso responden a ella. Otras estrategias de tratamiento, incluyendo las dosis elevadas de antipsicóticos o la potenciación con otros fármacos, siguen teniendo una evidencia limitada. La recuperación es un proceso complejo, no dependiente únicamente del tratamiento profesional, farmacológico o no. Los aspectos de soporte social y la generación de entornos favorables para la recuperación son esenciales para obtener evoluciones favorables y, lo más importante, vidas satisfactorias para nuestros pacientes, a pesar de su enfermedad.

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Emerging Treatments in Schizophrenia

Cited by 14 publications

References 35 publications

Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

Treating negative symptoms of schizophrenia: current approaches and future perspectives

Tratamiento farmacológico de la esquizofrenia y la esquizofrenia refractaria

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