ReviewSchizophrenia bulletin2020
Normalizing the Abnormal: Do Antipsychotic Drugs Push the Cortex Into an Unsustainable Metabolic Envelope?
Review in Schizophrenia bulletin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 2 of them syntheses 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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Bioenergetic impairment in schizophrenia: role of mitochondrial signaling in synaptic dysfunction - a systematic review.Frontiers in cell and developmental biology · 2026Pooled it
- Meta-analytic evidence of elevated choline, reduced N-acetylaspartate, and normal creatine in schizophrenia and their moderation by measurement quality, echo time, and medication status.NeuroImage. Clinical · 2023Pooled it
- Antipsychotics cause reversible structural brain changes within one week.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Linking Brain Morphometry to Psychometric Measures and Energy-Metabolic Biomarkers in Adults With Autism Spectrum Disorder.Autism research : official journal of the International Society for Autism Research · 2026Article
- Longitudinal brain structural changes during clozapine treatment: associations with neuroreceptor architecture and clinical response.medRxiv : the preprint server for health sciences · 2026Article
- Zinc Sulfate Alleviates Olanzapine Induced Alteration in Hepatic Protein Patterns and Antioxidant Defense System in Rats.Biological trace element research · 2026Article
- Molecular, physiological and functional features underlying antipsychotic medication use related cortical thinning.Translational psychiatry · 2025Article
- Response to clozapine in treatment resistant schizophrenia is related to alterations in regional cerebral blood flow.Schizophrenia (Heidelberg, Germany) · 2024Article
- Oxygen and the Spark of Human Brain Evolution: Complex Interactions of Metabolism and Cortical Expansion across Development and Evolution.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Article
- Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response.Psychological medicine · 2023Article
- Altered Patterns of Brain Glucose Metabolism Involve More Extensive and Discrete Cortical Areas in Treatment-resistant Schizophrenia Patients Compared to Responder Patients and Controls: Results From a Head-to-Head 2-[18F]-FDG-PET Study.Schizophrenia bulletin · 2023Article
- A Complex Systems Perspective on Neuroimaging Studies of Behavior and Its Disorders.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Schizophrenia: a disorder of broken brain bioenergetics.Molecular psychiatry · 2022Review
- Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
- Obstructive Sleep Apnea Is Treatable With Continuous Positive Airway Pressure in People With Schizophrenia and Other Psychotic Disorders.Schizophrenia bulletin · 2022Article
- Ethical concerns in the age of an advanced psychopharmacology.Journal of medical ethics and history of medicine · 2021Article
- Article
- N-acetylcysteine prevents olanzapine-induced oxidative stress in mHypoA-59 hypothalamic neurons.Scientific reports · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model.
Indexed as
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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.