Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study.
Adolescent
Adult
Cognitive Dysfunction
/ drug therapy
Double-Blind Method
Feasibility Studies
Female
Humans
Male
Nitric Oxide Donors
/ administration & dosage
Nitroglycerin
/ administration & dosage
Oral Sprays
Outcome Assessment, Health Care
Pilot Projects
Psychotic Disorders
/ complications
Young Adult
Clinical trial
glyceryl trinitrate
psychosis
schizophrenia
sodium nitroprusside
Journal
Journal of psychopharmacology (Oxford, England)
ISSN: 1461-7285
Titre abrégé: J Psychopharmacol
Pays: United States
ID NLM: 8907828
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
22
5
2020
medline:
5
11
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
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. We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 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 Analogue Scales). Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. We found no indication of an effect of GTN on symptoms of psychosis or cognition.
Sections du résumé
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
This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 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 Analogue Scales).
RESULTS
Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× 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.
Identifiants
pubmed: 32436761
doi: 10.1177/0269881120922967
pmc: PMC7376621
doi:
Substances chimiques
Nitric Oxide Donors
0
Oral Sprays
0
Nitroglycerin
G59M7S0WS3
Banques de données
ClinicalTrials.gov
['NCT02906553']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
839-847Références
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