Antipsychotic-treated Patients Research Articles

A miR-137–Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing

BackgroundmiR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing. MethodsUsing RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). ResultsIn 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. ConclusionsThe functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.

Extrapyramidal adverse events and anticholinergics use after the long-term treatment of patients with schizophrenia with the new long-acting antipsychotic Risperidone ISM®: results from matching-adjusted indirect comparisons versus once-monthly formulations of Paliperidone palmitate and Aripiprazole monohydrate in 52-week studies

BackgroundRisperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting.MethodsA literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints.ResultsThe analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses.ConclusionsThis MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting.

Dynamics of mental state and prolactin levels in patients with chronic schizophrenia during aripiprazole therapy

Introduction. Although scientific literature demonstrates a relationship between prolactin levels, the efficacy of aripiprazole therapy, and negative symptoms in patients with schizophrenia, many questions regarding these problems remain controversial.Objective to study dynamics of clinical and hormonal parameters in patients with chronic schizophrenia during aripiprazole therapy.Materials and methods: 60 patients with schizophrenia were studied: 42 male (70%) and 18 female (30%), aged 20 to 65 years (mean age 52.84±17.40 years) on inpatient aripiprazole treatment with the mean daily dosage of 15.33±4.52 mg. Comparative analysis of prolactin parameters was carried out taking into account the following factors: effectiveness of therapy, age, duration of the disease, severity of negative symptoms (according to the PANSS scores). Responders included patients with a reduction in total PANSS score of 20% and more.Results: the effectiveness of aripiprazole monotherapy after switching from previous antipsychotic treatment in patients with chronic schizophrenia was noted in 71.7% of patients. The effectiveness of therapy does not depend on the background values of the hormone: at high rates, prolactin levels decrease, and at low rates, they increase. Meanwhile, a certain pattern was revealed between the dynamics of scores of the negative PANSS scale and the level of prolactin: responders with high background levels showed the decrease of prolactin levels given the decline of the PANSS scores, and in responders with low values, the hormone levels increased. In non-responders, low background scores of the negative scale and their slight changes during therapy were accompanied by an increase in prolactin levels. The data obtained in relation to non-responder patients who showed negative correlations between the levels of prolactin, age, dosage of the drug and the duration of the disease require a more careful attitude to the appointment of aripiprazole due to the likelihood of a decrease in their prolactin levels to abnormally low values.

Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs-A Review.

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

Impact of adapted physical activity on hippocampal N-Acetyl Aspartate in patients with schizophrenia

IntroductionAdapted physical activity (APA) has beneficial neurobiological impact but the underlying pathophysiological mechanisms remain poorly described. APA is currently recognized as an adjuvant therapy to antipsychotic treatments in patients with schizophrenia (SCZs) to reduce the severity of negative symptoms and cognitive impairment. SCZs exhibit hippocampal N-acetylaspartate (NAA) reduction, a marker of neuronal viability and integrity whose concentrations can be assessed by proton magnetic resonance spectroscopy (1H-MRS).ObjectivesThe purpose of this study was to evaluate the impact of remote physical activity (e-APA) via the web on the NAA relative variations in the left hippocampus in SCZs compared to a patient control group benefiting from an health education program (HE). This study concerns one of the secondary objectives of the PEPsy V@SI study co-financed by the Pierre Deniker Foundation, the European Union and the Normandy Region within the framework of the FEDER/FSE 2014-2020 operational program.MethodsThirty-five SCZs were randomized in the e-APA active group or in the control group (HE). Participants received the interventions during 16 weeks, with two visioconference sessions per week. A 1H-MRS sequence positioned on the left hippocampus (MRI-3T) was acquired before and after both interventions. Absolute NAA concentrations in the left hippocampus were obtained using Osprey software after partial volume correction. After checking the quality criteria, the spectra of 6 SCZs in the e-APA group and 8 SCZs in the HE group were analyzed. To test the difference between interventions on the NAA relative variations, a Wilcoxon-Mann-Whitney test and effect size were performed. Paired Wilcoxon tests were used in each group before and after the interventions.ResultsNo significant difference was found in NAA relative variations in the left hippocampus between the e-APA group and the HE group (p = 0.18), although the effect size was 0.38 (considered as moderate). However, a trend towards an increase of NAA was observed in the e-APA group (before intervention: 12.08 International Units (I.U); after: 13.81 I.U) (p = 0.06) but not in the HE group (before intervention: 13.75 I.U ; after: 13.85 I.U) (p = 0.84).ConclusionsOur results showed a NAA significant increase in SCZs after an e-APA program, indicating a beneficial impact of e-APA on neuronal viability that might reflect an hippocampal plasticity. However, this increase did not differ significantly between active and control groups probably due to a weak statistical power.Disclosure of InterestL. Metivier: None Declared, F. Briend: None Declared, M. Tréhout: None Declared, L. Bigot: None Declared, G. Quarck: None Declared, A. Herbinet: None Declared, E. Leroux: None Declared, S. Dollfus Consultant of: Fabre,Gedeon,Roche and Takeda, inivited Conferences by Lundbeck, Otsuka, Janssen ; at contracts with Prophase MedAvances and NeuroCogTrials

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST)

Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94-1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Lundbeck and Otsuka.

High Rate of Discontinuation during Long-Acting Injectable Antipsychotic Treatment in Patients with Psychotic Disorders

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients' characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients' treatment adherence, thus preventing the long-term disability caused by psychotic disorders.

Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial

Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin, N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The “Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)” is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing. Clinical trial registration:http://www.drks.de/DRKS00029044 and https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044

Levels of Acylcarnitines and Branched-Chain Amino Acids in Antipsychotic-Treated Patients with Paranoid Schizophrenia with Metabolic Syndrome.

Several studies have shown that patients with schizophrenia are at high risk for metabolic syndrome (MetS) and bioenergetic dysfunction. Because acylcarnitines are involved in bioenergetic pathways and reflect the functioning of mitochondria, we hypothesized that these compounds are biomarkers of MetS in schizophrenia. The aim of this work was to quantify acylcarnitines and branched-chain amino acids in patients with schizophrenia comorbid with MetS. The study included 112 patients with paranoid schizophrenia treated with antipsychotics. Among them, 39 subjects met criteria of MetS. Concentrations of 30 acylcarnitines and three amino acids in dry serum spots were measured by liquid chromatography coupled with tandem mass spectrometry. MetS patients were found to have higher levels of valeryl carnitine (C5), leucine/isoleucine, and alanine as compared with patients without MetS, indicating possible participation of these compounds in the pathogenesis of metabolic disorders in schizophrenia. In patients with paranoid schizophrenia with or without MetS, lower levels of carnitines C10, C10:1, C12, and C18 were recorded as compared with the healthy individuals (n = 70), implying deterioration of energy metabolism. We believe that this finding can be explained by effects of antipsychotic medication on an enzyme called carnitine-palmitoyl transferase I.

Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia.

BackgroundPimavanserin prolongs the QT interval, with mean increases in corrected QT (QTc) of 5–8 ms, and is currently being investigated for the treatment of negative symptoms of schizophrenia.ObjectivesTo assess QT interval prolongation in 3 studies investigating once-daily pimavanserin as an adjunct to current antipsychotic treatment in patients with schizophrenia.MethodsElectrocardiograms were unblinded from trials in which pimavanserin or placebo was added to main antipsychotics over 6 weeks (ENHANCE), 26 weeks (ADVANCE), and up to 78 weeks (ongoing 52-week, open-label extension study [study 035]) of treatment. Antipsychotic treatment was permitted throughout these studies. The 3 most frequently used antipsychotic treatments were examined—aripiprazole (including long-acting injectable), risperidone (including long-acting injectable), and olanzapine. QT intervals were corrected (QTc) using Fridericia's method, with elevated risk defined as either postbaseline value maximum of >500 ms or change from baseline to postbaseline maximum of >60 ms.ResultsOf patients treated with adjunctive pimavanserin in ENHANCE, there were no postbaseline QTc values >481 ms; one patient in each of the risperidone and aripiprazole groups had change from baseline to postbaseline maximum >60 ms. More patients had change from baseline to postbaseline maximum ranging from 31 to 60 ms in the risperidone plus adjunctive placebo group (n = 5; 6.6%) than those in the risperidone plus adjunctive pimavanserin group (n = 3, 4.1%). In the pimavanserin plus antipsychotic group of ADVANCE, one patient had postbaseline QTc value >481 ms, and one patient treated with aripiprazole had change from baseline to postbaseline maximum of >60 ms. In study 035, a change from double-blind baseline to overall postbaseline maximum >60 ms occurred in one patient treated with aripiprazole and pimavanserin and in one patient treated with risperidone and pimavanserin. Similar proportions of patients had changes from double-blind baseline to post double-blind baseline maximum between 31 and 60 ms across treatments. No adverse events associated with an increase in the QTc interval were reported.ConclusionsAdjunctive pimavanserin with background antipsychotic treatment showed no evidence of QTc prolongation >500 ms postbaseline, consistent with previously reports on QT prolongation with pimavanserin.

Deprescribing of antipsychotic drugs for dementia : Recommendations for action on dose reduction and discontinuation attempts

HintergrundIn Leitlinien zur Behandlung von psychischen und Verhaltenssymptomen bei Demenz („Behavioral and Psychological Symptoms of Dementia“ [BPSD]) wird empfohlen, Antipsychotika im Falle einer notwendigen Therapie zeitlich begrenzt und in möglichst geringer Dosis einzusetzen.FragestellungUm das Bewusstsein für die Risiken einer Antipsychotikabehandlung bei Patient:innen mit Demenz und die dadurch begründete Notwendigkeit einer zeitlich begrenzten und möglichst niedrig dosierten Antipsychotikabehandlung zu schärfen, wurden Handlungsempfehlungen zum Deprescribing von Antipsychotika bei Menschen mit Demenz entwickelt.Material und MethodenDie Entwicklung der Handlungsempfehlungen erfolgte in einem mehrstufigen Prozess: 1. Literaturrecherche unter besonderer Würdigung von konsentierten Leitlinienempfehlungen und Ergebnissen einer eigenen Interventionsstudie (READY-Studie), 2. Diskussion und Konsentierung in einem Expert:innengremium, 3. Onlineumfrage von in Deutschland tätigen ärztlichen Demenzexpert:innen.ErgebnisseAus 51 im ersten Entwurf zusammengestellten Aussagen wurden nach der Diskussion im multiprofessionellen Expert:innengremium 32 Aussagen zum „Deprescribing“ (Reduktion und Ausschleichen) von Antipsychotika formuliert. 25 der 32 Aussagen wurden nach Konsentierung in einer Onlineumfrage durch ärztliche Demenzexpert:innen final übernommen.DiskussionIn Deutschland gibt es bislang keine konkreten Empfehlungen zur Vorgehensweise bei Reduktion und Absetzen von Antipsychotika, die zur Behandlung von BPSD bei Menschen mit Demenz eingesetzt werden. Die vorgelegte Arbeit soll als Handlungsempfehlung für Haus- und Fachärzt:innen dienen. Bei den Empfehlungen handelt es sich um keine Leitlinien, sie ersetzen nicht die Eigenverantwortlichkeit der Behandelnden und das individuell notwendige Vorgehen in Abhängigkeit von der Behandlungssituation.Zusatzmaterial onlineDie Onlineversion dieses Beitrags (10.1007/s00115-022-01343-w) enthält zusätzliches Material. Beitrag und Zusatzmaterial stehen Ihnen auf www.springermedizin.de zur Verfügung. Bitte geben Sie dort den Beitragstitel in die Suche ein, die Videos finden Sie beim Beitrag unter „Ergänzende Inhalte“.

The Role of Forensic Investigation in an Unusual Case of Patricide by a Schizophrenic Woman Involving Dismemberment of a Decomposed Body.

Dismemberment is characterized by the fragmentation of the body into anatomical sections. It can occur because of a murder, suicide, or accident. In the literature, there are no cases of patricide perpetrated by a daughter in which the offender performed the dismemberment. However, in this paper, we reported a case of patricide by a schizophrenic daughter that was not treated with antipsychotic therapy. Post-mortem Computed Tomography (PMCT), autopsy, and histological examinations were performed. The soft tissues were removed through maceration techniques and chemical treatment. An analysis was performed to study the bone margins and clarify the weapon and manner of death. This investigation, which used radiological and histological studies, helped to assess the vitality of the injuries. The purpose of the study is to discover the weapon used, the cause, and the manner of death, with particular interest in this case due to the dismemberment. Moreover, we emphasize the correlation between patricide, dismemberment, and a lack of antipsychotic treatment in patients with schizophrenia.

Mortality Among Parkinson's Disease Patients Treated With Pimavanserin or Atypical Antipsychotics: An Observational Study in Medicare Beneficiaries.

Pimavanserin, a serotonin 5-HT2 antagonist, is indicated for treatment of hallucinations and delusions associated with Parkinson's disease psychosis. In premarketing trials in patients with Parkinson's disease psychosis, 11% of patients died during open-label pimavanserin treatment. Antipsychotics, which are used off-label in Parkinson's disease psychosis, increase mortality in dementia patients. The authors compared mortality with pimavanserin and atypical antipsychotics in a large database. This was a retrospective new-user cohort study of Medicare beneficiaries with Parkinson's disease initiating pimavanserin (N=3,227) or atypical antipsychotics (N=18,442) from April 2016 to March 2019. All-cause mortality hazard ratios and 95% confidence intervals were estimated for pimavanserin compared with atypical antipsychotics, using segmented proportional hazards regression over 1-180 and 181+ days of treatment. Potential confounding was addressed through inverse probability of treatment weighting (IPTW). Pimavanserin users had a mean age of approximately 78 years, and 45% were female. Before IPTW, some comorbidities were more prevalent in atypical antipsychotic users; after IPTW, comorbidities were well balanced between groups. In the first 180 days of treatment, mortality was approximately 35% lower with pimavanserin than with atypical antipsychotics (hazard ratio=0.65, 95% CI=0.53, 0.79), with approximately one excess death per 30 atypical antipsychotic-treated patients; however, during treatment beyond 180 days, there was no additional mortality advantage with pimavanserin (hazard ratio=1.05, 95% CI=0.82, 1.33). Pimavanserin showed no mortality advantage in nursing home patients. Pimavanserin use was associated with lower mortality than atypical antipsychotic use during the first 180 days of treatment, but only in community-dwelling patients, not nursing home residents.

Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study

BackgroundCardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment.We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. MethodsData were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. ResultsAt the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X2 = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X2 = 16.151; p < 0.001) and high blood pressure (X2 = 10.654; p = 0.001). ConclusionsHaving a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

Prevalence of treatment resistant schizophrenia according to minima TRRIP criteria in a mental health catchment area in southern Spain

IntroductionThe response to antipsychotic treatment in patients with schizophrenia varies from 14 to 34% in first episodes, and from 45 to 61% in more chronic patients. Nevertheless, the concept of treatment resistant schizophrenia (TRS) is still a matter of great controversy. Recently, an international group of experts has developed the TRRIP criteria to define treatment resistant schizophrenia (TRS), including an ultra-resistance category for clozapine resistant patients. Up till now, there is a scarcity of epidemiological data of TRS with TRRIP criteria.ObjectivesThis study attempts to identify the population diagnosed of schizophrenia that fulfils the minima TRRIP criteria for TRS in our mental health catchment area.MethodsA descriptive and retrospective study has been developed on the patients diagnosed of schizophrenia (ICD.10, F.20) in the catchment area of the Mental Health Service at Jerez Hospital between 2018 and 2019. TRRIP criteria were applied for two independent researchers and, in case of disagreement, consensus was reached by using the LEAD procedure.ResultsThe total number of ICD-10 schizophrenic patients identified was 590, from a population of 456.752 in 2019. A group of these, 206 patients (35%) qualified as TRS according to the minima TRRIP criteria, 50% were positive subtype and the rest the negative one. 46.8% were treated with clozapine.ConclusionsConsensus criteria of TRS minimise the heterogeneity of epidemiological data in literature. Our data suggest a prevalence rate of TRS lower than that of similar studies. Accordingly, a comprehensive understanding of this population would undoubtedly contribute to improve preventive and therapeutic strategies.DisclosureNo significant relationships.

COVID-related hospitalization, intensive care treatment, and all-cause mortality in patients with psychosis and treated with clozapine

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this.

Evaluation of the Efficacy and Safety of Adding Pregabalin to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Double-blind Placebo-controlled Clinical Trial

Objectives: This study aims to evaluate the efficacy and safety of adding pregabalin to standard antipsychotic treatment in patients with chronic schizophrenia. Methods: In this randomized, double-blind, placebo-controlled clinical trial, participants were 48 male inpatients aged 18-65 years with chronic schizophrenia but with clinically stable conditions. They were randomly divided into two groups of intervention (n=24) and control (n=24). The intervention group received 75 mg of pregabalin per day for three weeks which was increased to 150 mg per day from the fourth week to the end of the study, in addition to standard antipsychotic medication for six weeks. The severity of psychotic symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), and their movement disorder symptoms were evaluated by the Barnes Akathisia Rating Scale (BARS) and Simpson-Angus Scale (SAS) at baseline and at 3th and 6th weeks of the intervention. Collected data were analyzed using repeated measures ANOVA in SPSS v.20 software, considering P&lt;0.05 as the statistically significance level. Results: No significant differences were observed in severity of disease based on the PANSS total score and its three subscales (positive scale, negative scale, and general psychopathology) and in the BARS and SAS scores at the end of 6th week in groups and between the two groups. Conclusion: Adding 150 mg of pregabalin to the standard antipsychotic treatment of patients with chronic schizophrenia is not effective in improving their psychotic symptoms, but it is well tolerated.

Distinct neuroanatomic subtypes in antipsychotic-treated patients with schizophrenia classified by the predefined classification in a never-treated sample.

Distinct neuroanatomic subtypes have been identified in never-treated patients with schizophrenia based on cerebral structural abnormalities, but whether antipsychotic-treated patients would be stratified under the guidance of such previously formed classification remains unclear. The present study aimed to investigate alterations of brain structures in antipsychotic-treated patients with schizophrenia based on a predefined morphological classification and their relationships with cognitive performance. Cortical thickness, surface area, and subcortical volume were extracted from 147 antipsychotic-treated patients with schizophrenia using structural magnetic resonance imaging for classification. The Brief Assessment of Cognition in Schizophrenia (BACS) and Positive and Negative Syndrome Scale (PANSS) were used to assess cognition and symptoms. Antipsychotic-treated patients were categorized into three subtypes with distinct patterns of brain morphological alterations. Subtypes 1 and 2 were characterized by widespread deficits in cortical thickness but relatively limited deficits in surface area. In contrast, subtype 3 demonstrated cortical thickening mainly in parietal-occipital regions and widespread deficits in surface area. All three subgroups demonstrated cognitive deficits compared with healthy controls. Significant associations between neuroanatomic and cognitive abnormalities were only observed in subtype 1, where cortical thinning in the left lingual gyrus was conversely related to symbol coding performance. Similar to drug-naïve patients, neuroanatomic heterogeneity exists in antipsychotic-treated patients, with disparate associations with cognition. These findings promote our understanding of relationships between neuroanatomic abnormalities and cognitive performance in the context of heterogeneity. Moreover, these results suggest that neurobiological heterogeneity needs to be considered in cognitive research in schizophrenia.

A Noninterventional Cohort Study Assessing Time to All-Cause Treatment Discontinuation After Initiation of Aripiprazole Once Monthly or Daily Oral Atypical Antipsychotic Treatment in Patients With Recent-Onset Schizophrenia.

Introduction: Aripiprazole once-monthly 400 mg (extended-release injectable suspension) is effective in long-term maintenance treatment of schizophrenia based on clinical studies. As study results may not reflect clinical practice, we compared treatment persistence with aripiprazole once-monthly 400 mg versus daily oral atypical antipsychotics in a naturalistic setting.Methods: This was an observational, noninterventional study of patients (aged 18-35 years) with recent-onset schizophrenia (< 5 years post diagnosis) who initiated maintenance treatment with aripiprazole once-monthly 400 mg or any daily oral atypical antipsychotic during a schizophrenia-related hospitalization or within 3 months post hospital discharge (timeframe: July 13, 2017-July 31, 2019). Data were from patient files/obtained during routine visits. Patients were followed for ≤ 12 months or until all-cause treatment discontinuation (including lost to follow-up), whichever came first. Data were analyzed using a sample constructed with inverse probability of treatment weighting (IPTW).Results: Among 357 patients (aripiprazole once-monthly 400 mg: 215, oral atypical antipsychotics: 142), all-cause treatment discontinuation occurred in 87 (41%) of aripiprazole once-monthly 400 mg, 68 (48%) of oral atypical antipsychotic patients over 52 weeks. In the IPTW sample, time to all-cause discontinuation was significantly different between both groups in favor of aripiprazole once-monthly 400 mg (hazard ratio = 1.46; 95% CI, 1.05-2.03; P = .023). Generalizability of results to the overall population with schizophrenia was limited due to incomplete overlap of patient characteristics between cohorts. The primary reason for treatment discontinuation in both groups was voluntary discontinuation by subject (aripiprazole once-monthly 400 mg: 11%; oral atypical antipsychotics: 8%).Conclusions: In a naturalistic setting, younger patients with recent-onset schizophrenia treated with aripiprazole once-monthly 400 mg after hospitalization tended to discontinue treatment later than patients treated with daily oral atypical antipsychotics.Trial Registration: ClinicalTrials.gov identifier: NCT03130465.

A nationwide study of the risk of all-cause, sudden death, and cardiovascular mortality among antipsychotic-treated patients with schizophrenia in Taiwan

IntroductionStudies have reported higher risks of mortality for patients with schizophrenia, compared to the general population. This study aimed to evaluate the risk of all-cause, sudden death, and cardiovascular mortality among patients with schizophrenia in terms of types of antipsychotics. MethodsA retrospective cohort study assessed the risk of mortality among antipsychotic-treated patients with schizophrenia. The study linked the Taiwan National Health Insurance (NHI) claims and National Register of Death databases from 2001 to 2015. Patients were hierarchically assigned to the following index antipsychotic treatment groups: atypical long acting injection (LAI), typical LAI, atypical oral, and typical oral. ResultsA total of 68,159 antipsychotic-treated patients with schizophrenia were analyzed. Under the hierarchical grouping, the largest percentages of patients were on atypical oral antipsychotic regimens (65.51%), followed by typical oral (14.00%), typical LAI (12.84%), and atypical LAI (7.65%). Typical oral patients had the highest incidence of all-cause mortality of 27.48 per 1000 patient-years and the atypical LAI group had the lowest incidence (13.95 per 1000 patient-years). Compared to typical oral users, there were lower risks of all-cause mortality for users of atypical LAI (aHR = 0.62, 95% CI: 0.47–0.81), typical LAI (aHR = 0.65, 95% CI: 0.55–0.78), and atypical orals (aHR = 0.55, 95% CI: 0.49–0.62). ConclusionCompared to typical oral users, we found a lower risk of all-cause mortality, sudden death, and cardiovascular mortality among schizophrenia users of LAIs and oral atypicals. Further research is warranted to characterize the risk of mortality among users of more recently available LAIs in the Asia Pacific region and elsewhere.