Study protocol for A randomized controlled trial with Rituximab for Psychotic disorder in adults (RCT-Rits) DOI Creative Commons

Susanne Bejerot,

Daniel Eklund, Hugo Hesser

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 6, 2023

Abstract Background: The role of inflammation in the aetiology schizophrenia has gained wide attention and research on association shows an exponential growth last 15 years. Autoimmune diseases severe infections are risk factors for later development schizophrenia, elevated inflammatory markers childhood or adolescence associated with a greater adulthood, individuals have increased levels pro-inflammatory cytokines compared to healthy controls, autoimmune overrepresented schizophrenia. However, treatments anti-inflammatory agents so far doubtful clinical relevance. primary objective this study is test whether monoclonal antibody rituximab, directed against B-cell antigen CD20 ameliorates psychotic symptoms adults schizoaffective disorder examine potential mechanisms. A secondary characteristics inflammation-associated psychosis identify pre-treatment biochemical rituximab responders. third interview subset patients informants their experiences trial obtain insights that rating scales may not capture. Methods: proof-of-concept employing randomised, parallel-group, double-blind, placebo-controlled design testing effect depletion psychosis. 120 participants diagnosis spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion (1000 mg) saline. Psychiatric measures blood samples be collected at baseline, week 12, 24 post-infusion. Brief assessments also made weeks 2 7. Neuroimaging lumbar puncture, both optional, performed baseline endpoints. Approximately 40 interviewed qualitative analyses perceived changes well-being emotional qualities, addition views research. Discussion: This first RCT investigating add-on treatment unselected SSD patients. If helpful, it transform disorders. It heighten awareness immune-psychiatric reduce stigma. Trial registration: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14 th October 2022.

Language: Английский

Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review DOI Creative Commons
A. Messina, Carmen Concerto, Alessandro Rodolico

et al.

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(6), P. 957 - 957

Published: June 15, 2023

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie clinical expressiveness disease, neuronal disconnections represent only an epiphenomenon. In recent years, several studies have converged on hypothesis microglia hyperactivation consequent neuroinflammatory state as pathogenic substrate schizophrenia. Prenatal, perinatal, postnatal factors can cause to switch from M2 anti-inflammatory M1 pro-inflammatory states. A continuous mild progressively leads loss, reduction dendritic spines, myelin degeneration. The augmentation drugs reduce neuroinflammation antipsychotics could be effective therapeutic modality managing This review will consider which with neuroprotective properties been used addition antipsychotic treatment patients

Language: Английский

Citations

24
Circular reasoning concerning Red flags for predicting rituximab response in OCD DOI Creative Commons
Susanne Bejerot,

A. Hietala,

Annika Söderbergh

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

0
IUPHAR review: Drug Repurposing in Schizophrenia – An Updated Review of Clinical Trials DOI Creative Commons
Jihan K. Zaki, Jakub Tomasik,

Sabine Bahn

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107633 - 107633

Published: Jan. 1, 2025

There is an urgent need for mechanistically novel and more efficacious treatments schizophrenia, especially those targeting negative cognitive symptoms with a favorable side-effect profile. Drug repurposing-the process of identifying new therapeutic uses already approved compounds-offers promising approach to overcoming the lengthy, costly, high-risk traditional CNS drug discovery. This review aims update our previous findings on clinical repurposing pipeline in schizophrenia. We examined studies conducted between 2018 2024, 61 trials evaluating 40 unique repurposed candidates. These encompassed broad range pharmacological mechanisms, including immunomodulation, enhancement, hormonal, metabolic, neurotransmitter modulation. A notable development combination muscarinic modulators xanomeline, compound antipsychotic properties, trospium, included mitigate peripheral side effects, now by FDA as first decades fundamentally mechanism action. Moving beyond dopaminergic paradigm such highlight opportunities improve treatment-resistant alleviate adverse effects. Overall, evolving landscape illustrates significant shift rationale schizophrenia development, highlighting potential silico strategies, biomarker-based patient stratification, personalized that align underlying pathophysiological processes.

Language: Английский

Citations

0
IUPHAR Review - Novel therapeutic targets for schizophrenia treatment: a translational perspective DOI Creative Commons
Veronica Begni,

Alessia Marchesin,

Marco Andrea Riva

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107690 - 107690

Published: March 1, 2025

Schizophrenia is a severe and debilitating psychiatric disorder that profoundly impacts cognitive, emotional, social functioning. Despite its devastating personal societal toll, current treatments often provide only partial relief, underscoring the urgent need for innovative therapeutic strategies. This review explores emerging approaches target complex neurobiological underpinnings of schizophrenia, moving beyond traditional dopamine-centric models. Among these, some novel drugs still employ multimodal mechanisms, simultaneously targeting dopaminergic serotonergic systems to enhance efficacy tolerability. Given well-documented excitatory/inhibitory imbalance in significant efforts have been directed toward addressing NMDA receptor hypofunctionality. However, strategies this pathway yet demonstrate consistent clinical efficacy. In contrast, therapies cholinergic system shown greater promise. For instance, xanomeline-trospium combination, which modulates muscarinic receptors, has recently gained approval, other molecules with similar mechanisms are currently under development. Beyond these approaches, being explored pathways, including neuroplasticity, neuroinflammation, mitochondrial dysfunction. These designed as part combinatorial strategy available antipsychotic drugs. progress, challenges remain translating experimental discoveries into effective applications. Future research should prioritize biomarker-driven precision medicine optimize individualized treatment outcomes. By integrating targets, schizophrenia may evolve more comprehensive personalized approach, disorder's full spectrum symptoms improving patient quality life.

Language: Английский

Citations

0
Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits) DOI Creative Commons

Susanne Bejerot,

Daniel Eklund, Hugo Hesser

et al.

BMC Psychiatry, Journal Year: 2023, Volume and Issue: 23(1)

Published: Oct. 23, 2023

The role of inflammation in the aetiology schizophrenia has gained wide attention and research on association shows an exponential growth last 15 years. Autoimmune diseases severe infections are risk factors for later development schizophrenia, elevated inflammatory markers childhood or adolescence associated with a greater adulthood, individuals have increased levels pro-inflammatory cytokines compared to healthy controls, autoimmune overrepresented schizophrenia. However, treatments anti-inflammatory agents so far doubtful clinical relevance. primary objective this study is test whether monoclonal antibody rituximab, directed against B-cell antigen CD20 ameliorates psychotic symptoms adults schizoaffective disorder examine potential mechanisms. A secondary characteristics inflammation-associated psychosis identify pre-treatment biochemical rituximab responders. third interview subset patients informants their experiences trial obtain insights that rating scales may not capture.A proof-of-concept employing randomised, parallel-group, double-blind, placebo-controlled design testing effect depletion psychosis. 120 participants diagnosis spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion (1000 mg) saline. Psychiatric measures blood samples be collected at baseline, week 12, 24 post-infusion. Brief assessments also made weeks 2 7. Neuroimaging lumbar puncture, both optional, performed baseline endpoints. Approximately 40 interviewed qualitative analyses perceived changes well-being emotional qualities, addition views research.This first RCT investigating add-on treatment unselected SSD patients. If helpful, it transform disorders. It heighten awareness immune-psychiatric reduce stigma.NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th October 2022.

Language: Английский

Citations

6
Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders DOI Creative Commons
Per Thunberg,

David Fresnais,

Paul B. Hamilton

et al.

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 41, P. 100864 - 100864

Published: Sept. 16, 2024

Language: Английский

Citations

2
Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment DOI Creative Commons
Maike Gallwitz, Isa Lindqvist, Jan Mulder

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 21, 2024

Language: Английский

Citations

1
Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings DOI Creative Commons
Khoa D. Nguyen, Andrea Amerio, Andrea Aguglia

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(16), P. 2099 - 2099

Published: Aug. 19, 2023

Schizophrenia is a complex psychiatric condition that may involve immune system dysregulation. Since most putative disease mechanisms in schizophrenia have been derived from genetic association studies and fluid-based molecular analyses, this review aims to summarize the emerging evidence on clinical correlates dysfunction disorder. We conclude by attempting develop unifying hypothesis regarding relative contributions of microglia various cell populations development schizophrenia. This provide important translational insights can become useful for addressing multifaceted presentation

Language: Английский

Citations

3
Obsessive-Compulsive Disorder during the COVID-19 Pandemic DOI Creative Commons

Federica Fiaschè,

Georgios D. Kotzalidis,

Alessandro Alcibiade

et al.

Psychiatry International, Journal Year: 2023, Volume and Issue: 4(2), P. 102 - 104

Published: April 21, 2023

The COVID-19 pandemic was followed by lifestyle changes worldwide [...]

Language: Английский

Citations

2
Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment DOI Creative Commons
Janet L. Cunningham, Maike Gallwitz, Isa Lindqvist

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Abstract Obsessive compulsive disorder (OCD) is a debilitating condition affecting about 2% of the population where half patients do not respond to standard treatment. The emerging concept an autoimmune OCD subgroup grounded on findings that suggest immunological aetiology. We here present longitudinal clinical course for three severely ill, functionally impaired complex cases with chronic treatment-resistant OCD. In all cases, off-label treatment rituximab was followed by clear and sustained gains regarding symptom burden function over several years. phenotypes red flags are described in detail. Antibodies targeting mouse brain tissue were detected cerebral spinal fluid cases. report exploratory analyses markers proteomics include elevated levels sCD27 indicative complement pathway activation CSF when compared controls. Multidisciplinary collaboration, advanced investigations feasible psychiatric setting. case histories provide proof principle newly proposed criteria biological measures may predict response provides orientation inform hypotheses design future trials.

Language: Английский

Citations

0