ArticleFrontiers in psychiatry2022
Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.
Article in Frontiers in psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04789915 (AMEND - Add-on MEmaNtine to Dopamine Modulation to Improve Negative Symptoms at First Psychosis), which is not on this map. Cited by 7 papers.
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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.
AMEND - Add-on MEmaNtine to Dopamine Modulation to Improve Negative Symptoms at First Psychosis
Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
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- Longitudinal metabolome profiling from pregnancy through childhood and risk of neurodevelopmental disorders at age 10.Nature communications · 2026Article
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Pharmacological Treatments of Negative Symptoms in Schizophrenia-An Update.Journal of clinical medicine · 2024Review
- Mechanisms of Ferritinophagy and Ferroptosis in Diseases.Molecular neurobiology · 2024Review
- Multinuclear Magnetic Resonance Spectroscopy at Ultra-High-Field: Assessing Human Cerebral Metabolism in Healthy and Diseased States.Metabolites · 2023Review
- Polypharmacy in Older Adults with Alzheimer's Disease.Medicina (Kaunas, Lithuania) · 2022Review
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Antipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis. Aims: This investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine. Materials and Equipment: Antipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment. Outcome Measures: The primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes. Anticipated Results: We hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning. Perspectives: By combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04789915].
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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.