Effects of sodium nitroprusside in the prevention of schizophrenia-like symptoms induced by ketamine – A translational double-blind study

Abstract

Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

An Overview of Animal Models Related to Schizophrenia

“…In healthy subjects, SNP was able to prevent psychogenic symptoms induced by ketamine. 111 Other studies by the same group in rats showed that a single dose of SNP prevented psychosis-like behaviour produced by ketamine 112 and that SNP treatment more consistently decreased ketamine-induced behaviours than other NO-related compounds. 113 Thus, in these SNP studies, basic science research findings in animal models were translated to the clinical situation, then reverse translated back to animal models to further investigate mechanisms of action and other potential therapies.…”

Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial

“…Improvement in psychotic symptoms was observed in patients with schizophrenia treated with SNP (Hallak et al, 2013) although other studies failed to replicate this finding (Brown et al, 2019; Stone et al, 2016). Recently Rezende et al (Rezende et al, 2017) found that SNP may prevent some psychiatric symptoms, measured with the Brief Psychiatric Rating Scale (BPRS), induced by ketamine administration in healthy controls.…”