Background There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. Aims We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. Methods Single-centre, randomized, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 x sprays of GTN or placebo for 3 consecutive days, and re-assessed on Days 1,2,3,7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond–Lader Visual Analog Scales). Results Nineteen patients were randomised, thirteen participants were included in the analyses. Compared to placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2x more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. Conclusions We found no indication of an effect of GTN on symptoms of psychosis or cognition. Funding Guys & St Thomas’ Charity (EFT150704)
Original languageEnglish
JournalJournal of Psychopharmacology
Publication statusAccepted/In press - 5 Apr 2020


  • Nitric oxide donor
  • sodium nitroprusside
  • Psychosis
  • schizophrenia
  • Clinical trial
  • glyceryl trinitrate


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