Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside

Hallak, Jaime E. C.; Maia‐de‐Oliveira, João Paulo; Abrão, João; Évora, Paulo Roberto Barbosa; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Belmonte-de-Abreu, Paulo; Baker, Glen B.; Dursun, Serdar

doi:10.1001/jamapsychiatry.2013.1292

Cited by 127 publications

(168 citation statements)

References 25 publications

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“…In line with these assumptions, a recent study demonstrated that a single dose of an NO donor was able to significantly reduce schizophrenia symptoms rapidly (4h) after infusion, and that this effect was detectable for almost 4 weeks (Hallak et al, 2013). Thus, genetic data informing about reduced NOS1 expression might well provide information on which patients would best benefit from such an intervention in the sense of personalized medicine.…”

Section: Discussionmentioning

confidence: 89%

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

Weber

Klamer

Freudenberg

et al. 2014

European Neuropsychopharmacology

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NO is a pleiotropic signaling molecule and has an important role for cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adaptor protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratios of 1.29 in the metaanalysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia.

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Section: Discussionmentioning

confidence: 89%

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

Weber

Klamer

Freudenberg

et al. 2014

European Neuropsychopharmacology

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“…One RCT in the systematic review assessed NIT as an intervention for the management of schizophrenia (Hallak et al, 2013). In this double-blind RCT (conducted in a single center in Brazil), the researchers aimed to assess the efficacy and safety of a single intravenous administration of NIT (0.5 mcg kg -1 min.…”

Section: Sodium Nitroprussidementioning

confidence: 99%

“…Concurrent with the development of new drugs, there are new indications and off-label uses of several drugs such as sodium nitroprusside (NIT) (Barnes et al, 2011;Hallak et al, 2013). The therapeutic merits of the intravenous formulation of NIT were initially described in 1800, and its clinical use has been established since 1929 for the treatment of severe hypertension (Coyle, 2013).…”

Section: Introductionmentioning

confidence: 99%

<b>New drugs for the treatment of agitation in schizophrenia: a systematic review and meta-analysis of inhaled loxapine and infused sodium nitroprusside

Tonin¹,

Piazza²,

Borba³

et al. 2017

Acta Sci. Health Sci.

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ABSTRACT. The use of novel drugs such as inhaled loxapine (LOXi) for schizophrenia and the off-label use of substances such as sodium nitroprusside (NIT) for the management of mental disorders require further investigation. We aimed to evaluate the efficacy and safety of LOXi and NIT for the treatment of agitation associated with schizophrenia. A systematic review of randomized controlled trials (RCTs) comparing the use of LOXi or NIT versus placebo or other antipsychotic agents was conducted, and we evaluated the efficacy (CGI-scale) and safety (adverse events) of the therapies. Altogether, 71 studies were identified, of which 2 (LOXi) were included in the meta-analysis, and 1 (NIT) was included in the systematic review only. The efficacy data showed superiority of LOXi against placebo, regardless of the dose (5 and 10 mg). No significant differences were observed concerning the safety results. Treatment with NIT showed favorable results, with significant reduction of the symptoms. The efficacy of these medications is difficult to assess because of the lack of RCTs. However, there is some information regarding the efficacy and safety of LOXi in the treatment of agitation in schizophrenic patients.Keywords: antipsychotic agents, mental disorders, evidence-based medicine.Novos fármacos para o tratamento da agitação na esquizofrenia: revisão sistemática e meta-análise da loxapina inalável e nitroprussiato de sódio RESUMO. Fármacos mais recentes como a loxapina inalável (LOXi) para o tratamento da esquizofrenia e o uso off-label de substâncias como o nitroprussiato de sódio (NIT) para o manejo de desordens mentais requerem mais investigações. O objetivo do estudo foi avaliar eficácia e segurança da LOXi e do NIT para tratamento da agitação na esquizofrenia. Foi realizada revisão sistemática de ensaios clínicos randomizados (ECR) comparando o uso de LOXi ou NIT versus placebo ou outros antipsicóticos. Foram avaliados desfechos de eficácia (escala CGI-I) e segurança (eventos adversos). Ao todo 71 estudos foram identificados, dos quais dois foram incluídos nas meta-análises (ambos da LOXi) e 1 sobre NIT foi incluído somente na revisão sistemática. Os dados de eficácia demonstraram superioridade da LOXi frente ao placebo, independente das doses avaliadas (5 ou 10 mg). Não foram observadas diferenças significativas entre os resultados de segurança com o controle. O único estudo incluído sobre o NIT mostrou resultados favoráveis, com redução significativa dos sintomas. Apesar da carência de ECR com esses fármacos dificultar a determinação e a reunião de informações, há potenciais evidências de eficácia e segurança da LOXi no tratamento da agitação em pacientes com esquizofrenia.Palavras-chave: antipsicóticos, transtornos mentais, medicina baseada em evidências.

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“…The hypothesis that in schizophrenia there is a dysregulation of the NO-cGMP pathway 38 has been supported by recent experimental evidence. 39 A randomised, doubleblind, placebo controlled trial of slow intravenous infusion of nitroprusside in patients with an established diagnosis of schizophrenia presenting with an acute psychotic episode showed rapid and persistent improvement in both positive and negative symptoms. 39 Currently, the New York School of Medicine is rec ruiting participants for a phase II clinical trial (NCT02695589) to demonstrate the efficacy of nitroprusside in treating positive and negative symptoms.…”

Section: Current Development and Future Directionsmentioning

confidence: 99%

Pharmacological treatment of schizophrenia - a review of progress

Dimitrelis¹,

Shankar²

2016

Prog. Neurol. Psychiatry

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Since much of our knowledge about the neurobiology of schizophrenia derives from the initial discovery that chlorpromazine was effective in treating psychosis, pharmacological research has mostly concentrated on dopamine-blocking agents. Here, the authors discuss the situation where there is no single pharmacological agent on the horizon that could serve as the 'holy grail' to address the full range of symptoms of schizophrenia and what the immediate future holds with the widespread use of polypharmacy.

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Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside

Cited by 127 publications

References 25 publications

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

<b>New drugs for the treatment of agitation in schizophrenia: a systematic review and meta-analysis of inhaled loxapine and infused sodium nitroprusside

Pharmacological treatment of schizophrenia - a review of progress

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