Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- A phase 2 randomized controlled trial of luvadaxistat in treatment of adults with cognitive impairment associated with schizophrenia: results from the ERUDITE study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder.Schizophrenia (Heidelberg, Germany) · 2026Article
- D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.Cellular and molecular neurobiology · 2026Review
- Impact of D-Amino Acids in Schizophrenia.Biomolecules · 2025Review
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- [Cognitive impairments associated with schizophrenic psychoses : Diagnostics, course and therapy].Der Nervenarzt · 2025Review
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Interpretable machine learning to evaluate relationships between DAO/DAOA (pLG72) protein data and features in clinical assessments, functional outcome, and cognitive function in schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2025Article
- Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement.Biological psychiatry · 2025Review
- Overview of Novel Antipsychotic Drugs: State of the Art, New Mechanisms, and Clinical Aspects of Promising Compounds.Biomedicines · 2025Review
- Disturbances in Auditory and Visual Perceptual Function in Schizophrenia: Patterns, Causes, and Consequences.Current topics in behavioral neurosciences · 2025Review
- Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.The international journal of neuropsychopharmacology · 2024Review
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Treatment of Cognitive Impairment Associated with Schizophrenia Spectrum Disorders: New Evidence, Challenges, and Future Perspectives.Brain sciences · 2024Review
- Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.Molecular psychiatry · 2024Article
- Review
- Decreased free D-aspartate levels in the blood serum of patients with schizophrenia.Frontiers in psychiatry · 2024Article
- New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment.Frontiers in cellular neuroscience · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.