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

Hallak JC, Maia-de-Oliveira J, Abrao J, et al. — Wed, 08 May 2013 00:00:00 GMT

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

Nitric Oxide and Symptom Reduction in Schizophrenia

Coyle JT. — Wed, 08 May 2013 00:00:00 GMT

In this issue of the journal, Hallack et al report results from a placebo-controlled clinical trial showing that infusion of sodium nitroprusside causes a rapid and persistent reduction of symptoms in patients with schizophrenia who have been symptomatically stabilized with antipsychotic medications. The peer reviewers of the manuscript concurred that the study pointed to a potentially new avenue for pharmacologic intervention in schizophrenia, although they recognized that the small number of patients studied was a serious limitation. It is true that the field is littered with small trials with robust outcomes that ultimately are not replicated. However, the rationale for the study was tethered to an increasingly compelling body of evidence from drug challenges, postmortem analysis, and gene association studies that hypofunction of the N -methyl-D-aspartate (NMDA) receptor, a glutamate receptor subtype that mediates neural plasticity, is a core feature of schizophrenia. In particular, NMDA receptor hypofunction appears to be particularly relevant to negative symptoms and cognitive impairments in schizophrenia.

JAMA Psychiatry: Schizophrenia Topic Collection

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

Nitric Oxide and Symptom Reduction in Schizophrenia