Alterations in peripheral levels of cytokines and associated inflammatory markers in acute and chronic stages of schizophrenia spectrum disorders: a systematic review and network meta-analysis

Introduction It has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD). Objectives As there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network meta-analysis was performed. Methods Records from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls. Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls. Results After application of the screening process, 215 articles were included for data-analysis. One group of markers were consistently elevated (p<0·05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP). A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p<0·05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p<0·05) in chronic SSD. Conclusions These results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness. This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers. Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ). Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system. Disclosure of Interest None Declared

Introduction: Paliperidone Palmitate 3-month formulation (PP3M) has shown a significantly longer time to relapse compared to placebo, with similar efficacy and safety to Paliperidone Palmitate 1-month (PP1M) (Carpiniello et al. Drug Des. Devel. Ther. 2016;10 1731-1742).Objectives: The main objective of this study was to determine the effectiveness of PP3M in preventing hospital admissions and emergency room visits, in people with non-acute schizophrenia in a naturalistic psychiatric outpatient setting Methods: Sample: 30 people with diagnosis of schizophrenia (DSM 5 criteria), who had started treatment with PP3M, after being stabilized with PP1M (the dose was not modified in the four months prior to inclusion in the study) Quarterly basis, the following evaluations were performed during a follow-up period of 66 months: The Clinical Global Impression-Schizophrenia scale (CGI-SCH) Treatment adherence, concomitant medication and the number of hospitalizations and emergency visits Efficacy values: Percentage of patients who remained free of admissions at the end of 66 months of follow-up.
Other evaluation criteria: Percentage of patients who never visited the emergency department at the end of 66 months of follow-up.Average change from baseline visit to the final evaluation as assessed by score obtained on the following scale: GSI-SCH, percentage of patients on antipsychotic monotherapy and treatment adherence rate.Results: The mean dose of PP3M was 401.55 mg The percentage of patients who remained free of admissions at the end of the 66 months was 83.25% and the percentage of patients who never visited the emergency department at the end of 66 months was 79.92% Mean variations from baseline scores at 66 months were: (-0.36 AE0-37) on the GCI-SCH.The percentage of patients on antipsychotic monotherapy at the end of the 66 months was 76.56%The rate of adherence was 86.58% .Conclusions: In our study, we found that paliperidone palmitate 3-month formulation was effective in reducing the number of admissions and visits to the emergency department, under conditions of daily clinical practice.
Introduction: It has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD).Objectives: As there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network metaanalysis was performed.Methods: Records from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls.Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls.
Results: After application of the screening process, 215 articles were included for data-analysis.One group of markers were consistently elevated (p<0Á05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP).A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p<0Á05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p<0Á05) in chronic SSD.Conclusions: These results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness.This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers.Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ).Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system.

EPP0756
Clinical experiences with 6-monthly paliperidone palmitate after 12 months of use.A retrospective study Introduction: Long-acting injectable antipsychotics (LAIA) have provided a significant improvement in the treatment of schizophrenia.Although there is already significant clinical experience with paliperidone palmitate, it is important to evaluate the clinical response of patients to this new 6-monthly presentation, so descriptive studies based on real clinical evidence can be very useful for this purpose.Objectives: The main objective of the study is to describe the use of 6-monthly paliperidone palmitate in routine clinical practice, providing variables that objectify the evolution such as the number of admissions and visits to the emergency room.Methods: Retrospective descriptive study with a sample selected by non-probabilistic consecutive sampling, retrospective type, in a time interval of 12 months (n=40).The patients selected were all those who received 6-monthly paliperidone palmitate treatment, with a diagnosis of schizophrenia, in 12 months of use at Hospital Universitario Infanta Elena.A descriptive analysis was performed.Mean and standard deviation were calculated for quantitative variables and N and percentage for categorical variables.Results: A total of 40 administrations of 6-monthly paliperidone palmitate were performed in the study.None of the patients presented adverse reactions related to the administration of the drug, not reporting local pain or inflammation of the puncture area, except for the characteristic discomfort of an intramuscular puncture.Regarding the efficacy of 6-monthly paliperidone palmitate, none of the patients presented a psychotic decompensation after its administration, maintaining psychopathological stability after the change.The switch to 6-monthly paliperidone palmitate was made from both 1-monthly paliperidone palmitate and 3-monthly paliperidone palmitate, both showing the same efficacy.Regarding tolerability, all the patients who were administered 6-monthly paliperidone palmitate were previously treated with the monthly and quarterly presentation of the same molecule, having presented good tolerability to it, maintaining said tolerability after treatment.change to 6-monthly paliperidone palmitate, with no adverse reaction being recorded after the change.The adherence presented by the patients was very good, performing 100% of the administrations of 6-monthly paliperidone palmitate Conclusions: 6-monthly paliperidone palmitate may be an effective and well-tolerated treatment for the treatment of schizophrenia.
In the present study, the use of said LAIA in a group of 40 patients is objectified, showing excellent efficacy and tolerability.All study patients were already stable with the 1-monthly and 3-monthly paliperidone palmitate formulations, maintaining said psychopathological stability when switching to the 6-monthly paliperidone palmitate formulation, with excellent adherence and adverse effect profile .
Introduction: 6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate.Some patients do not have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitate.There is little clinical experience with these alternative initiations and through this work those that have been carried out for 12 months at the Hospital Universitario Infanta Elena are exposed.Objectives: The main objective of the study is to describe the alternative initiations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons.Methods: A retrospective selection of patients will be made through non-probabilistic consecutive sampling, including all patients who have been administered 6-monthly paliperidone palmitate with a start different from the standard during the last 4 months.To do this, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed an alternative initiation pattern.The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, and visits to the emergency room and admissions.