Importance: The currently available antipsychotic drugs do not benefit everyone and the burden of treatment-refractory schizophrenia remains an enormous personal, clinical and societal problem. However, a new approach may be considered , involving the dysregulation of the glutamate-nitric oxide (NO)- cyclic guanosine monophosphate (c-GMP) network [2-4]: sodium nitroprusside (SNP) is a drug that has been in clinical use since 1929 for severe hypertension. It is a powerful vasodilator and may facilitate glutamate release and modulate NMDA receptor activity  through the release of NO. Objective: The aim of this study is to examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside on the symptoms of a patient with treatment-refractory schizophrenia. Participant: This study is a case report on Mr S., a 45-yearold patient with a 25-year history of paranoid schizophrenia. He suffers from invasive and persistent intrapsychic hallucinations and persecutory delusions, occasionally causing fits of hostility and anger and depressive mood. His severe symptomatology is resistant to treatment (e.g. clozapine, electroconvulsive therapy, combination clozapine antipsychotics and/or mood stabilizers), resulting in his hospitalization for 25 years. Setting: This experiment has been conducted in Charles Nicolle University Hospital (Department of Anesthesiology) in Rouen, France. Intervention: SNP was administrated as an infusion of 0, 5 mg/ kg/min for 4 hours. The procedure was approved by the department of anesthesiology and a fully trained anesthetist was present during the infusion to ensure safety. Physiologic cardiovascular and pulmonary measures were recorded every 15 minutes to assess the safety of SNP. Main outcome measures: Positive and Negative Syndrome Scale (PANSS) was used to assess changes in severity of schizophrenia symptoms until 2 weeks after the infusion. The Udvalg for Kliniske Undersogelser (UKU) rating scale was used to prospectively assess the treatment adverse effects during this study. Results: After the infusion of SNP, we have observed a limited effectiveness on the psychopathologic and positive symptoms of schizophrenia in Mr S. Indeed, mean difference in PANSSpsychopathologic and positive subscale scores after and before the infusion was respectively -5% and -6% and scores went back up after 2 weeks. However, analysis of the PANNS-negative subscale scores revealed an improvement of negative symptoms in Mr S. In fact, mean PANNS-negative score after infusion has decreased by 15%, which persisted for 2 weeks. Concerning the safety, the infusion was well-tolerated, there was no significant hemodynamic change and results for the UKU did not indicate any adverse effects. Conclusion: The infusion of SNP did not reduce Mr S. hallucinations and delusions but did improve his negative symptoms for 2 weeks after the infusion, which is in accordance with recent findings. Indeed, patients with schizophrenia have been found to exhibit reduced NO metabolites, which is associated with negative symptoms of schizophrenia.
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