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Original Investigation |

Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside:  A Randomized, Double-blind, Placebo-Controlled Trial

Jaime E. C. Hallak, MD, PhD1,2; Joao Paulo Maia-de-Oliveira, MD1; Joao Abrao, MD, PhD1; Paulo R. Evora, MD, PhD1; Antonio W. Zuardi, MD, PhD1,2; Jose A. S. Crippa, MD, PhD1,2; Paulo Belmonte-de-Abreu, MD2,3; Glen B. Baker, PhD, DSc2,4,5; Serdar M. Dursun, MD, PhD, FRCPC2,4,5
[+] Author Affiliations
1Neuroscience and Behavior Department, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil
2National Institute of Science and Technology in Translational Medicine, Ribeirao Preto, Brazil
3Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
4Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada
5Centre for Psychiatric Assessment and Therapeutics, Alberta Health Services, Alberta Hospital Edmonton, Edmonton, Alberta, Canada
JAMA Psychiatry. 2013;70(7):668-676. doi:10.1001/jamapsychiatry.2013.1292.
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Importance  The treatment of schizophrenia remains a challenge, and the currently available antipsychotic drugs are slow acting and produce a number of adverse effects.

Objective  To examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside (0.5 μg/kg/min for 4 hours) on the positive, negative, anxiety, and depressive symptoms in patients with schizophrenia.

Design  Single-center, randomized, double-blind, placebo-controlled trial performed from March 9, 2007, to March 12, 2009.

Setting  University teaching hospital in São Paulo, Brazil.

Participants  Twenty inpatients aged 19 to 40 years with a diagnosis of schizophrenia who were in the first 5 years of the disease who are taking antipsychotics.

Intervention  Sodium nitroprusside administration.

Main Outcome Measures  The 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale.

Results  After the infusion of sodium nitroprusside, a rapid (within 4 hours) improvement of symptoms was observed. The placebo and experimental groups had significant differences in the 18-item Brief Psychiatric Rating Scale total score and subscale scores, which persisted for 4 weeks after infusion.

Conclusions  The results clearly show a therapeutic effect of sodium nitroprusside. If this drug is approved for routine clinical use in patients with schizophrenia, this discovery will be an important advance in the pharmacologic treatment of this devastating disorder.

Trial Registration  clinicaltrials.gov Identifier: NCT01548612

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Figures

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Figure 1.
Flowchart

Progress of the study participants throughout the study.

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Figure 2.
Mean Total 18-Item Brief Psychiatric Rating Scale Scores

A, Scores during the first 12 hours; B, scores at 4 weeks. Asterisks indicate statistically significant P values as given in the text; error bars, SEMs.

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Figure 3.
Individual Total 18-Item Brief Psychiatric Rating Scale Scores

Individual 18-item Brief Psychiatric Rating Scale (BPRS-18) total scores during the first 48 hours. A, Sodium nitroprusside group; B, placebo group.

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Figure 4.
Mean 18-Item Brief Psychiatric Rating Scale Subscale Scores

Mean 18-item Brief Psychiatric Rating Scale (BPRS-18) subscale scores during the first 48 hours and at 4 weeks. A, Thinking disorder scores; B, withdrawal-retardation scores; C, anxiety-depression scores; and D, activation scores. Asterisks indicate statistically significant P values as given in the text; error bars, SEMs.

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Figure 5.
Mean Positive and Negative Syndrome Scale Negative Subscale Scores

A, Scores during the first 12 hours; B, scores at 4 weeks. Asterisks indicate statistically significant P values as given in the text; error bars, SEMs.

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Figure 6.
Physiologic Cardiovascular and Pulmonary Measures During the Infusion

No significant changes were determined that would require clinical intervention, including systolic blood pressure (A), diastolic blood pressure (B), blood oxygen saturation (C), or heart rate (D). Error bars indicate SEMs.

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