T40. GLYCERYL TRINITRATE IN FIRST EPISODE PSYCHOSIS UNMEDICATED WITH ANTIPSYCHOTICS: A RANDOMISED CONTROLLED FEASIBILITY STUDY

Abstract 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 early phase studies of SNP in patients with psychosis have had mixed results, and the drug has to be administered intravenously. GTN is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. We explored the safety and effectiveness of GTN in unmedicated patients with a first episode of psychosis. Methods A single-centre, randomized, double-blind, placebo-controlled trial was conducted from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients with a first episode of psychosis were recruited from the South London and Maudsley NHS Trust, London, UK. Nineteen patients were randomised to receive 3 x sprays of GTN or placebo for 3 consecutive days, and re-assessed on Day 7. Thirteen participants were included in the final analyses. At each assessment point, symptom levels were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive performance was evaluated using the Jumping to Conclusions (JTC) and the Hopkins Verbal Learning (HVLT) tasks. Results Compared to placebo, GTN was well tolerated, but it was not associated with significant effects on either psychotic symptoms or cognition. Bayesian statistics indicated with moderate confidence that GTN does not have a therapeutic effect. Discussion This study indicates that nitric oxide donors are not therapeutically beneficial in psychosis. It also highlights the difficulties in recruiting unmedicated patients with psychosis. Future clinical trials would benefit from frameworks built into clinical services, to signpost patients not responding to medication and those discontinuing medication to clinical trials of alternatives.

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Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

Journal of Psychopharmacology ◽

10.1177/0269881120922967 ◽

2020 ◽

Vol 34 (8) ◽

pp. 839-847 ◽

Cited By ~ 1

Author(s):

Kate Merritt ◽

Ana Catalan ◽

Samuel Cowley ◽

Arsime Demjaha ◽

Matthew Taylor ◽

...

Keyword(s):

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Verbal Memory ◽

Alternative Hypothesis ◽

Controlled Trial ◽

Verbal Learning ◽

Nitric Oxide Donor ◽

Psychotic Symptoms ◽

First Episode ◽

Double Blind

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.

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Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial

The Lancet ◽

10.1016/s0140-6736(11)60971-9 ◽

2011 ◽

Vol 378 (9795) ◽

pp. 983-990 ◽

Cited By ~ 196

Author(s):

Heather Powell ◽

Vanessa E Murphy ◽

D Robin Taylor ◽

Michael J Hensley ◽

Kirsten McCaffery ◽

...

Keyword(s):

Nitric Oxide ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Exhaled Nitric Oxide ◽

Double Blind ◽

Randomised Controlled ◽

In Pregnancy

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A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18147239 ◽

2021 ◽

Vol 18 (14) ◽

pp. 7239

Author(s):

Itxaso González-Ortega ◽

Patricia Vega ◽

Enrique Echeburúa ◽

Susana Alberich ◽

Jessica Fernández-Sevillano ◽

...

Keyword(s):

Early Intervention ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

First Episode Psychosis ◽

Clinical Treatment ◽

Post Treatment ◽

Psychotic Symptoms ◽

First Episode ◽

Episode Psychosis ◽

Randomised Controlled

Introduction: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. Objectives: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. Patients and methods: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. Results: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. Conclusions: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.

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Quetiapinev.lithium in the maintenance phase following a first episode of mania: Randomised controlled trial

The British Journal of Psychiatry ◽

10.1192/bjp.bp.116.186833 ◽

2017 ◽

Vol 210 (6) ◽

pp. 413-421 ◽

Cited By ~ 29

Author(s):

Michael Berk ◽

Rothanthi Daglas ◽

Orwa Dandash ◽

Murat Yücel ◽

Lisa Henry ◽

...

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Lithium Treatment ◽

Controlled Trial ◽

Maintenance Phase ◽

Psychotic Symptoms ◽

First Episode ◽

General Functioning ◽

Randomised Controlled ◽

Clinical Trials Registry

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry – ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned andpost hoccomparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.

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Nitric oxide donors for patients undergoing IVF. A prospective, double-blind, randomized, placebo-controlled trial

Human Reproduction ◽

10.1093/humrep/17.10.2615 ◽

2002 ◽

Vol 17 (10) ◽

pp. 2615-2620 ◽

Cited By ~ 28

Author(s):

J. Ohl

Keyword(s):

Nitric Oxide ◽

Controlled Trial ◽

Nitric Oxide Donors ◽

Double Blind

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Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial

Journal of Psychopharmacology ◽

10.1177/0269881120985147 ◽

2021 ◽

Vol 35 (2) ◽

pp. 124-127

Author(s):

Laura Bevilacqua ◽

Alex Charney ◽

Charlotte R Pierce ◽

Samantha M Richards ◽

Manish K Jha ◽

...

Keyword(s):

Nitric Oxide ◽

Sodium Nitroprusside ◽

Mechanism Of Action ◽

Controlled Trial ◽

Nitric Oxide Donor ◽

Controlled Study ◽

Primary Role ◽

Double Blind ◽

Nitric Oxide Signaling ◽

Antidepressant Effects

Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects. Studies suggest that inhibition of nitric oxide synthesis plays a role in the mechanism of action of ketamine. This randomized, placebo-controlled study investigated whether co-administration of sodium nitroprusside, a nitric oxide donor, compared to placebo, would attenuate the antidepressant and dissociative effects of ketamine. Sixteen ketamine responders were randomized to a double-blind infusion of ketamine co-administered with placebo or sodium nitroprusside. Our findings show no difference between the two conditions suggesting that the nitric oxide pathway may not play a primary role in ketamine’s antidepressant or dissociative effects. The study is registered at clinicaltrials.gov (NCT03102736).

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