Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-29T01:27:15.972Z Has data issue: false hasContentIssue false
  • English
  • Français

The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial

Published online by Cambridge University Press:  22 September 2016

J. M. Stone ,
P. D. Morrison ,
I. Koychev ,
F. Gao ,
T. J. Reilly ,
M. Kolanko ,
A. Mohammadinasab ,
S. Kapur  and
P. K. McGuire
J. M. Stone*
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
P. D. Morrison
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
I. Koychev
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
F. Gao
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
T. J. Reilly
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
M. Kolanko
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
A. Mohammadinasab
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
S. Kapur
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
P. K. McGuire
Affiliation:
King's College London, Institute of Psychiatry Psychology and Neuroscience, London, UK
*
*Address for correspondence: Dr J. M. Stone, King's College London, Institute of Psychiatry Psychology and Neuroscience, De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.

Method

This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.

Results

SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.

Conclusions

Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.

Keywords

Clinical trialnitric oxideschizophreniasodium nitroprussidespatial working memory
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 16 , December 2016 , pp. 3443 - 3450
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bird, DC, Bujas-Bobanovic, M, Robertson, HA, Dursun, SM (2001). Lack of phencyclidine-induced effects in mice with reduced neuronal nitric oxide synthase. Psychopharmacology 155, 299–309.Google Scholar
Bujas-Bobanovic, M, Bird, DC, Robertson, HA, Dursun, SM (2000). Blockade of phencyclidine-induced effects by a nitric oxide donor. British Journal of Pharmacology 130, 1005–1012.CrossRefGoogle ScholarPubMed
Egerton, A, Brugger, S, Raffin, M, Barker, GJ, Lythgoe, DJ, McGuire, PK, Stone, JM (2012). Anterior cingulate glutamate levels related to clinical status following treatment in first-episode schizophrenia. Neuropsychopharmacology 37, 2515–2521.CrossRefGoogle ScholarPubMed
Hallak, JE, Maia-de-Oliveira, JP, Abrao, J, Evora, PR, Zuardi, AW, Crippa, JA, Belmonte-de-Abreu, P, Baker, GB, Dursun, SM (2013). Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial. JAMA Psychiatry 70, 668–676.CrossRefGoogle ScholarPubMed
Hoyt, KR, Tang, LH, Aizenman, E, Reynolds, IJ (1992). Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons. Brain Research 592, 310–316.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Kinon, BJ, Millen, BA, Zhang, L, McKinzie, DL (2015). Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. Biological Psychiatry 78, 754–762.Google Scholar
Maia-de-Oliveira, JP, Abrao, J, Evora, PR, Zuardi, AW, Crippa, JA, Belmonte-de-Abreu, P, Baker, GB, Dursun, SM, Hallak, JE (2015). The effects of sodium nitroprusside treatment on cognitive deficits in schizophrenia: a pilot study. Journal of Clinical Psychopharmacology 35, 83–85.Google Scholar
Maia-de-Oliveira, JP, Belmonte-de-Abreu, P, Bressan, RA, Cachoeira, C, Baker, GB, Dursun, SM, Hallak, JE (2014). Sodium nitroprusside treatment of clozapine-refractory schizophrenia. Journal of Clinical Psychopharmacology 34, 761–763.Google Scholar
Manzoni, O, Prezeau, L, Desagher, S, Sahuquet, A, Sladeczek, F, Bockaert, J, Fagni, L (1992). Sodium nitroprusside blocks NMDA receptors via formation of ferrocyanide ions. Neuroreport 3, 77–80.Google Scholar
Merritt, K, Egerton, A, Kempton, MJ, Taylor, MJ, McGuire, PK (2016). Nature of glutamate alterations in Schizophrenia: a meta-analysis of proton magnetic resonance spectroscopy studies. JAMA Psychiatry 73, 665–674.Google Scholar
Oh, S, McCaslin, PP (1995). The iron component of sodium nitroprusside blocks NMDA-induced glutamate accumulation and intracellular Ca2+ elevation. Neurochemical Research 20, 779–784.CrossRefGoogle ScholarPubMed
Overall, JE, Goram, DR (1962). The brief psychiatric rating scale. Psychological Reports 10, 799–812.Google Scholar
Piskulic, D, Olver, JS, Norman, TR, Maruff, P (2007). Behavioural studies of spatial working memory dysfunction in schizophrenia: a quantitative literature review. Psychiatry Research 150, 111–121.Google Scholar
Sahakian, BJ, Morris, RG, Evenden, JL, Heald, A, Levy, R, Philpot, M, Robbins, TW (1988). A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain 111, 695–718.CrossRefGoogle ScholarPubMed
Shuto, M, Ogita, K, Minami, T, Maeda, H, Yoneda, Y (1997). Inhibition of [3H]MK-801 binding by ferrous (II) but not ferric (III) ions in a manner different from that by sodium nitroprusside (II) in rat brain synaptic membranes. Journal of Neurochemistry 69, 744–752.Google Scholar
Stone, JM (2011). Glutamatergic antipsychotic drugs: a new dawn in the treatment of schizophrenia? Therapeutic Adances in Psychopharmacology 1, 5–18.Google Scholar
Wass, C, Archer, T, Palsson, E, Fejgin, K, Alexandersson, A, Klamer, D, Engel, JA, Svensson, L (2006). Phencyclidine affects memory in a nitric oxide-dependent manner: working and reference memory. Behavioural Brain Research 174, 49–55.Google Scholar