The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial

Psychol Med. 2016 Dec;46(16):3443-3450. doi: 10.1017/S0033291716002245. Epub 2016 Sep 22.


Background: Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.

Method: This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 ( identifier: NCT02176044). Twenty patients with schizophrenia aged 18-60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.

Results: SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.

Conclusions: Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.

Keywords: Clinical trial; nitric oxide; schizophrenia; sodium nitroprusside; spatial working memory.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Memory, Short-Term*
  • Middle Aged
  • Nitroprusside / therapeutic use*
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / physiopathology
  • Psychotic Disorders / psychology
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Spatial Memory*
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use*
  • Young Adult


  • Vasodilator Agents
  • Nitroprusside

Associated data