Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in
Schizophrenia

Amerio, Andrea; Magnani, Luca; Arduino, Gabriele; Fesce, Fabio; de Filippis, Renato; Parise, Alberto; Costanza, Alessandra; Nguyen, Khoa D.; Saverino, Daniele; De Berardis, Domenico; Aguglia, Andrea; Escelsior, Andrea; Serafini, Gianluca; De Fazio, Pasquale; Amore, Mario

doi:10.2174/1570159x22666231128101725

Cited by 5 publications

(1 citation statement)

References 198 publications

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“…A widely accepted hypothesis formulates that inappropriate pruning contributes to the pathomechanism of schizophrenia, and it might relate to the elevated level of cytokines and inflammatory factors. Since dopamine receptors D1 and D2 are expressed by microglia as well, the dopamine-antagonist psychotropic agents can modulate microglial activity and may exert a favorable effect for patients by this mechanism as well [ 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis

Jezsó,

Kálmán,

Farkas

et al. 2024

Biomolecules

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Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action.

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Section: Introductionmentioning

confidence: 99%

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis

Jezsó,

Kálmán,

Farkas

et al. 2024

Biomolecules

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Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database

de Filippis,

Kane,

Arzenton

et al. 2024

Drug Saf

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Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. Methods We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions. Results A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9–1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1–2.5; IC 1.2, 95% CI 1.1–1.3), cyamemazine (ROR 2.3, 95% CI 1.5–3.5; IC 1.2, 95% CI 0.5–1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1–2.1; IC 0.6, 95% CI 0.1–1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases ( p = 0.03). Fatal cases were 164 (10.7%). Conclusions Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians’ awareness leading to safer prescribing of antipsychotics. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-024-01431-7.

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Impact of second-generation antipsychotics monotherapy or combined therapy in cytokine, lymphocyte subtype, and thyroid antibodies for schizophrenia: a retrospective study

Guo,

Kong,

Wen

et al. 2024

BMC Psychiatry

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Background Schizophrenia (SCZ) shares high clinical relevance with the immune system, and the potential interactions of psychopharmacological drugs with the immune system are still an overlooked area. Here, we aimed to identify whether the second-generation antipsychotics (SGA) monotherapy or combined therapy of SGA with other psychiatric medications influence the routine blood immunity biomarkers of patients with SCZ. Methods Medical records of inpatients with SCZ from January 2019 to June 2023 were retrospectively screened from June 2023 to August 2023. The demographic data and peripheral levels of cytokines (IL-2, IL-4, IL-6, TNF-α, INF-γ, and IL-17 A), lymphocyte subtype proportions (CD3+, CD4+, CD8 + T-cell, and natural killer (NK) cells), and thyroid autoimmune antibodies (thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb)) were collected and analyzed. Results 30 drug-naïve patients, 64 SGA monotherapy (20 for first-episode SCZ, 44 for recurrent SCZ) for at least one week, 39 combined therapies for recurrent SCZ (18 with antidepressant, 10 with benzodiazepine, and 11 with mood stabilizer) for at least two weeks, and 23 used to receive SGA monotherapy (had withdrawn for at least two weeks) were included despite specific medication. No difference in cytokines was found between the SGA monotherapy sub-groups ( p > 0.05). Of note, SGA monotherapy appeared to induce a down-regulation of IFN-γ in both first (mean [95% confidence interval]: 1.08 [0.14–2.01] vs. 4.60 [2.11–7.08], p = 0.020) and recurrent (1.88 [0.71–3.05] vs. 4.60 [2.11–7.08], p = 0.027) episodes compared to drug-naïve patients. However, the lymphocyte proportions and thyroid autoimmune antibodies remained unchanged after at least two weeks of SGA monotherapy ( p > 0.05). In combined therapy groups, results mainly resembled the SGA monotherapy for recurrent SCZ ( p > 0.05). Conclusion The study demonstrated that SGA monotherapy possibly achieved its comfort role via modulating IFN-γ, and SGA combined therapy showed an overall resemblance to monotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12888-024-06141-z.

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Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia

Cited by 5 publications

References 198 publications

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis

Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database

Impact of second-generation antipsychotics monotherapy or combined therapy in cytokine, lymphocyte subtype, and thyroid antibodies for schizophrenia: a retrospective study

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