Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial

Wang, Xiujuan; Zhao, Jian; Hu, Yunqing; Jiao, Zhiqiang; Lu, Yanli; Ding, Mingmin; Kou, Yanna; Li, Benliang; Meng, Fancui; Zhao, Haijian; Li, Hong; Li, Wenqiang; Yang, Yongfeng; Lv, Luxian

doi:10.1016/j.psychres.2018.08.079

Cited by 16 publications

(27 citation statements)

References 36 publications

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“…In one study, 42 adults with schizophrenia were randomized to two placebo or sodium nitroprusside infusions (0.5 μg/kg per min for 4 h) during a 1-week interval. 61 The authors failed to find any significant effect of sodium nitroprusside vs. placebo on psychotic symptoms or cognitive functions, although sodium nitroprusside seemed relatively well tolerated. In a second study, 20 patients with a diagnosis of schizophrenia or schizoaffective disorder were randomized to an infusion of sodium nitroprusside (0.5 μg/kg per min for 4 h) or placebo and reassessed for symptoms and cognitive performance immediately after the infusion, and 4 weeks later (Table 2).…”

Section: Sodium Nitroprusside (Nitric Oxide Donor)mentioning

confidence: 97%

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

et al. 2019

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Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine’s efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

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Section: Sodium Nitroprusside (Nitric Oxide Donor)mentioning

confidence: 97%

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

et al. 2019

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“…In 2013, Hallak and colleagues reported that SNP, delivered intravenously as an adjunct to antipsychotic medication, was effective in reducing acute psychotic symptoms in patients in the early phase of psychosis (Hallak et al, 2013a). However, subsequent studies in patients with chronic schizophrenia have not replicated this finding (Brown et al, 2019;Stone et al, 2016;Wang et al, 2018). It has been argued that SNP may only be effective in the early phases of psychosis in patients who have received relatively little antipsychotic treatment (Maia-De-Oliveira et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…In previous trials, SNP was tested as an adjunct to antipsychotic medication, with the placebo-control condition consisting of patients receiving placebo in addition to antipsychotic medication. All trials showed an improvement in symptoms with SNP + an adjunct antipsychotic; however, the three negative trials also reported a significant improvement in symptoms for the placebo arm (those receiving placebo + antipsychotic) (Brown et al, 2019;Stone et al, 2016;Wang et al, 2018). Therefore, the efficacy of SNP may be masked by the response to the existing antipsychotic, and so there is a need to test nitric oxide donors in patients unmedicated with antipsychotics to determine its true efficacy.…”

Section: Introductionmentioning

confidence: 99%

Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

Merritt

Catalán

Cowley³

et al. 2020

J Psychopharmacol

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Background: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. Aims: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. Methods: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond–Lader Visual Analogue Scales). Results: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. Conclusions: We found no indication of an effect of GTN on symptoms of psychosis or cognition.

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“…-BOBANOVIC et al, 2000;KANDRATAVICIUS et al, 2015;SAMPAIO et al, 2018). (STONE et al, 2016;WANG et al, 2018;WANG et al, 2019) ON (RAMIREZ et al, 2004;KIM, 2008;NAKANO et al, 2010) e de GMPc (GATTAZ et al, 1983), quando comparados com sujeitos normais. Na linha dessas evidências, estudos em roedores que foram submetidos a inibição farmacológica e genética da síntese e transmissão do glutamato e do ON, evidenciaram que esses animais passaram a desenvolver comportamento psychosis like após tais…”

Section: Grupos De Ratos Fêmeas Nps/cbdunclassified

“…Essa mesma limitação se aplicaria ao estudo de Lecointre et al (2014) descrito acima, que não encontrou aumento da atividade locomotora horizontal em ratos fêmeas, mas sim nos machos, pois seria possível, por exemplo, que esses ratos fêmeas estivessem em proestrus. TITULAER et al, 2019) e também negativos (STONE et al, 2016;HURTUBISE et al, 2017;WANG et al, 2018;WANG et al, 2019), ou utilizada em estudos de caráter preventivo, também com desfechos positivos e promissores (DIANA et al, 2018). , 2009).…”

Section: Distância Total Percorridaunclassified

Efeitos de doses repetidas do nitroprussiato de sódio ou do canabidiol no período de maturação cerebral em um modelo animal de esquizofrenia

Prado¹

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Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial

Cited by 16 publications

References 36 publications

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

Efeitos de doses repetidas do nitroprussiato de sódio ou do canabidiol no período de maturação cerebral em um modelo animal de esquizofrenia

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