Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders – A comprehensive systematic review and meta-analysis

Jeppesen, Rose; Christensen, Rune Haubo Bojesen; Pedersen, Emilie M.J.; Nordentoft, Merete; Hjorthøj, Carsten; Köhler‐Forsberg, Ole; Benros, Michael E.

doi:10.1016/j.bbi.2020.08.028

Cited by 82 publications

(53 citation statements)

References 142 publications

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“…Anti-inflammatory agents have shown some benefits as adds-ons to antipsychotic treatment in schizophrenia, as reported by two recent meta-analyses[ 100 , 101 ]. A meta-analysis of 62 double-blind randomized clinical trials studying aspirin, celecoxib, omega-3 fatty acids, estrogens, pregnenolone, minocycline, N-acetyl cysteine, and erythropoietin in 2914 patients found an overall significant effect of a decrease in the PANSS score[ 100 ].…”

Section: Neuroinflammationmentioning

confidence: 99%

“…Another meta-analysis of 70 randomized clinical trials including 4104 subjects investigated either primarily non-steroidal anti-inflammatory drugs (NSAIDs), minocycline and monoclonal antibodies, or drugs with potential anti-inflammatory properties (N-acetyl cysteine, melatonin, neurosteroids, estrogens, fatty acids, statins, and glitazones) as adjunctive therapies to antipsychotics. The analysis also found a decrease in the PANSS score[ 101 ]. Small but significant effect sizes were observed on both negative and positive symptoms, general psychopathology and working memory.…”

Section: Neuroinflammationmentioning

confidence: 99%

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Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Ľupták¹,

Michaličková²,

Fišar³

et al. 2021

WJP

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Schizophrenia is a severe psychiatric disorder characterized by emotional, behavioral and cognitive disturbances, and the treatment of schizophrenia is often complicated by noncompliance and pharmacoresistance. The search for the pathophysiological mechanisms underlying schizophrenia has resulted in the proposal of several hypotheses to explain the impacts of environmental, genetic, neurodevelopmental, immune and inflammatory factors on disease onset and progression. This review discusses the newest insights into the pathophysiology of and risk factors for schizophrenia and notes novel approaches in antipsychotic treatment and potential diagnostic and theranostic biomarkers. The current hypotheses focusing on neuromediators (dopamine, glutamate, and serotonin), neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, and oxidative stress are summarized. Key genetic features, including small nucleotide polymorphisms, copy number variations, microdeletions, mutations and epigenetic changes, are highlighted. Current pharmacotherapy of schizophrenia relies mostly on dopaminergic and serotonergic antagonists/partial agonists, but new findings in the pathophysiology of schizophrenia have allowed the expansion of novel approaches in pharmacotherapy and the establishment of more reliable biomarkers. Substances with promising results in preclinical and clinical studies include lumateperone, pimavanserin, xanomeline, roluperidone, agonists of trace amine-associated receptor 1, inhibitors of glycine transporters, AMPA allosteric modulators, mGLUR 2-3 agonists, D-amino acid oxidase inhibitors and cannabidiol. The use of anti-inflammatory agents as an add-on therapy is mentioned.

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Section: Neuroinflammationmentioning

confidence: 99%

Section: Neuroinflammationmentioning

confidence: 99%

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Ľupták¹,

Michaličková²,

Fišar³

et al. 2021

WJP

View full text Add to dashboard Cite

show abstract

“…Immunopsychiatry is an emerging research area investigating immune dysregulation in the pathogenesis of mental disorders, with specific regard to depression [24,25]. Recently, several meta-analyses documented clinical depression as a pro-inflammatory state [26,27], and anti-inflammatory added on standard treatment showed improvement of psychotic disorders [28]. The two dimensions, the psychological and the biological, must always be kept together; only in this way can we explain why inflammation can, for example, make a person less available to novelties (by altering the hippocampus and substantia nigra) [29] and more willing to see dangers rather than opportunities (by altering the ventral striatum) [30], as experimental studies on healthy volunteers showed, who were subjected to inflammatory stimuli while their brain was in the functional magnetic resonance scanner.…”

Section: Inflamed Mindmentioning

confidence: 99%

Nutrition, Exercise, and Stress Management for Treatment and Prevention of Psychiatric Disorders. A Narrative Review Psychoneuroendocrineimmunology-Based

Bottaccioli

Marzola

et al. 2021

Endocrines

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Psychoneuroendocrineimmunology (PNEI) brings together knowledge acquired since the 1930s from endocrinology, immunology, neuroscience, and psychology. With PNEI, a model of research and interpretation of health and disease is emerging, which sees the human body as a structured and interconnected unit, where the psychological and biological systems are mutually coordinated. In the PNEI view, many factors could influence mental health, with the endocrine system involved in mediating the effects of environmental stress on mental health and inflammation in the onset and course of psychiatric disorders as a result of individual and collective conditions and behaviors. Among these, nutrition is one way by which the environment impacts physiology: indeed, many pieces of research showed that several elements (e.g., probiotics, fish oil, zinc) have a positive effect on mental disorders thus being potentially augmentation agents in treatment. Still, physical activity can moderate depressive symptoms, while prolonged stress increases the risk of psychopathology. Taken together, the PNEI-based approach may inform prevention and treatment strategies, also in the field of mental health care.

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“…The study of immune-modulating treatments for psychiatric disorders has definitely gained traction in the last two decades, and meta-analyses demonstrating the benefit of celecoxib and/or minocycline are now available for schizophrenia, bipolar disorder and major depressive disorder ( Bavaresco et al., 2019 ; Cakici et al., 2019 ; Jeppesen et al., 2020 ; Na et al., 2014 ; Rosenblat et al., 2016 ; Rosenblat and McIntyre, 2018 ; Xiang et al., 2017 ). Yet none of these treatment options have been included in official clinical guidelines.…”

Section: Science-to-policy Transformationmentioning

confidence: 99%

The future of immunopsychiatry: Three milestones to clinical innovation

Picker

2021

Brain, Behavior, & Immunity - Health

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Psychoneuroimmunology, the area of research dedicated to understanding the fundamental interactions between the central nervous system and the immune system, has given rise to the development of Immunopsychiatry, a new discipline which harnesses the immune system to produce beneficial outcomes for mental health problems. Immunopsychiatry has the potential to become a clinically relevant specialty area in psychiatric practice, but has not yet been adopted by the wider mental health community. This paper aims to map out the future trajectory of Immunopsychiatry on its road towards science-to-policy knowledge translation and clinical implementation. Three critical milestones which will need to be reached in order for Immunopsychiatry to fulfil its promise for clinical innovation are discussed: a clear definition of patients who fall within the immunopsychiatric continuum; demonstration of well-defined clinical benefit and incorporation in clinical guidelines; and convergence with other paradigms in biological psychiatry.

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Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders – A comprehensive systematic review and meta-analysis

Cited by 82 publications

References 142 publications

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Nutrition, Exercise, and Stress Management for Treatment and Prevention of Psychiatric Disorders. A Narrative Review Psychoneuroendocrineimmunology-Based

The future of immunopsychiatry: Three milestones to clinical innovation

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