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

Tatiana M N Rezende, J. P. Maia-De-Oliveira, Ludmyla Kandratavicius, João P. Machado‐de‐Sousa, João Abrão, D. A. Prado, Rodrigo A. Bressan, Acioly L T Lacerda, A. Zuardi, Glen B. Baker, Serdar Dursun, J. Hallak

December 1, 2017 DOI: 10.1590/0101-60830000000141 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind
Sample size 38
Population Healthy human subjects
Interventions Sodium nitroprusside ketamine
Dose SNP: 0.15, 0.25, and 0.5 mcg/kg/min; ketamine: 0.26 mg/kg bolus then 0.25 mg/kg/h for 50 minutes
Duration SNP infusion over 75 minutes; ketamine maintenance for 50 minutes
Measures Brief Psychiatric Rating Scale, Clinician-Administered Dissociative States Scale, facial emotion and identity recognition tasks
Topics Esketamine Ketamine
Key findings Sodium nitroprusside reduced ketamine-induced psychopathological alterations and dissociative symptoms in healthy subjects, and protected against ketamine-induced impairments in facial emotion and identity recognition, suggesting preventative properties against psychotic manifestations.

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. Rezende TMN et al. / Arch Clin Psychiatry. 2017;44(6):149-53

Comparable studies

Other randomized controlled trials on ketamine, most cited first.

Study Year Design Participants
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community 1994 Randomized controlled trial n = 19
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery 2005 Randomized controlled trial n = 75
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers 2000 Single-blind placebo-controlled study n = 20

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