Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.

PURPOSE: Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder. METHODS: A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use. RESULTS: Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine. CONCLUSION: Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.

Clozapine-induced myocarditis: electronic health register analysis of incidence, timing, clinical markers and diagnostic accuracy.

BACKGROUND: Clozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences. AIMS: To examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects. METHOD: A retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined. RESULTS: Of 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation. CONCLUSIONS: Suspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The 'critical period' for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.

A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis.

BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored. AIMS: This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period. METHOD: Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication. RESULTS: Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14-1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11-1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling. CONCLUSIONS: Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

[THERE IS ROOM FOR IMPROVEMENT: THE RATE OF CLOZAPINE USE AMONG PATIENTS WITH SCHIZOPHRENIA IN ISRAEL].

BACKGROUND: About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment. OBJECTIVES: To assess, for the first time in Israel, the rate of clozapine use in patients with schizophrenia. METHODS: A retrospective cohort study of "Clalit Health Services" electronic records was conducted. People diagnosed with schizophrenia (F.20 ICD 10 code) who had at least one prescription filled for clozapine were followed up between 2012 and 2014. RESULTS: Of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. In addition, 60% of patients with clozapine had polytherapy with other antipsychotic compound or lithium. Polytherapy was associated with HR of 2.1 for morality during the follow-up period. CONCLUSIONS: Clozapine is underutilized in Israel, similar to reports from other countries. Moreover, the data suggests that when treatment is given it is not optimized, as reflected by high rates of polytherapy associated with increased mortality. Using therapeutic drug monitoring, now available in Israel, for clozapine might increase clozapine dosage optimization.

Attitudes of mental health clinicians toward perceived inaccuracy of a schizophrenia diagnosis in routine clinical practice.

BACKGROUND: Mental health clinicians have previously been reported to express reservations regarding the utility and accuracy of the psychiatric classification systems. In this study we aimed to examine clinicians' experiences with instances of perceived inaccuracy of a schizophrenia diagnosis. METHODS: Mental health clinicians (N = 175) participated in an online survey assessing prevalence and perceived reasons for inaccuracies of a schizophrenia diagnosis. Respondents included psychiatric ward directors (13.1%), senior psychiatrists and psychologists (40.5%), and psychiatry and clinical psychology residents (36%). RESULTS: Fifty-three percent of respondents reported encountering instances where a schizophrenia diagnosis was assigned even though clinical presentation did not match diagnostic criteria. Seventy-three percent of senior psychiatrists in a position to determine a diagnosis declared assigning schizophrenia even when controversial among clinical staff, and 15% of them declared doing so frequently. The likelihood of frequently assigning a schizophrenia diagnosis even when clearly controversial was predicted by the perception that an inaccurate diagnosis is assigned due to the presence of negative symptoms (OR 2.20, 95% CI 1.04-4.66, p = 0.039) and due to patient-related factors, such as the need to facilitate rehabilitation (OR 1.77, 95% CI 1.07-2.90, p = 0.024). CONCLUSIONS: Although a schizophrenia diagnosis is considered relatively stable and clear, our study indicates that, in clinical practice, the assignment of this diagnosis is frequently controversial. These controversies are associated with the perception that an inaccurate diagnosis is assigned due to diagnostic considerations, or due to the possibility that patients might benefit from such a diagnosis. Implications and limitations for psychiatric practice and discourse are discussed.

Listening to the Patient Perspective: Psychiatric Inpatients' Attitudes Towards Physical Restraint.

When other options fail, physical restraint is used in inpatient psychiatric units as a means to control violent behavior of agitated inpatients and to prevent them from harm. The professional and social discourse regarding the use of restrictive measures and the absence of the inpatients' attitudes towards these measures is notable. Our research therefore tries to fill this gap by interviewing inpatients about these issues. To assess the subjective experience and attitudes of inpatients who have undergone physical restraint. Forty inpatients diagnosed with psychiatric disorders were interviewed by way of a structured questionnaire. Descriptive statistics were conducted via use of SPSS statistical software. 1.Inpatients reported that physical restraint evoked an experience of loneliness (77.5%) and loss of autonomy (82.5%). 2.Staff visits during times of physical restraint were reported as beneficial according to 73.6% of the inpatients interviewed. 3.Two thirds of the inpatients viewed the use of physical restraints as justified when an inpatient was dangerous. 4.Two thirds of the inpatients regarded physical restraint as the most aversive experience of their hospitalization. Our pilot study explored the subjective experience and attitudes of psychiatric inpatients towards the use of physical restraint. Inpatients viewed physical restraint as a practice that was sometimes justified but at the same time evoked negative subjective feelings. We conclude that listening to inpatients' perspectives can help caregivers to evaluate these measures.

Author Correction: Listening to the Patient Perspective: Psychiatric Inpatients' Attitudes Towards Physical Restraint.

The original version of this article unfortunately contained a mistake in the author group section. The correct name of the second author is "Saed Maree" and the third author is "Aviv Segev."

Possible Biases of Researchers' Attitudes Toward Video Games: Publication Trends Analysis of the Medical Literature (1980-2013).

BACKGROUND: The study of video games is expanding, and so is the debate regarding their possible positive and deleterious effects. As controversies continue, several researchers have expressed their concerns about substantial biases existing in the field, which might lead to the creation of a skewed picture, both in the professional and in the lay literature. However, no study has tried to examine this issue quantitatively. OBJECTIVE: The objective of our study was to examine possible systematic biases in the literature, by analyzing the publication trends of the medical and life sciences literature regarding video games. METHODS: We performed a complete and systematic PubMed search up to December 31, 2013. We assessed all 1927 articles deemed relevant for their attitude toward video games according to the focus, hypothesis, and authors' interpretation of the study results, using a 3-category outcome (positive, negative, and neutral). We assessed the prevalence of different attitudes for possible association with year of publication, location of researchers, academic discipline, methodological research, and centrality of the publishing journals. RESULTS: The attitude toward video games presented in publications varied by year of publication, location, academic discipline, and methodological research applied (P<.001 for all). Moreover, representation of different attitudes differed according to centrality of the journals, as measured by their impact factor (P<.001). CONCLUSIONS: The results suggest that context, whether scientific or social, is related to researchers' attitudes toward video games. Readers, both lay and professional, should weigh these contextual variables when interpreting studies' results, in light of the possible bias they carry. The results also support a need for a more balanced, open-minded approach toward video games, as it is likely that this complex phenomenon carries novel opportunities as well as new hazards.

Navigating the straits of deprescribing: Psychiatrist's personal account of fears and hopes.

Deprescribing is a long-overdue concept for psychiatrists and therapists, presenting potentially more sophisticated approaches to psychiatric care. This approach is fueled by both scientific pursuits and contemporary social ideologies that underscore the pivotal role of a patient's values and their freedom of choice. Indeed, deprescribing is well woven with modern liberal and progressive values. Yet, amidst the emphasis on these aspects, it is crucial not to lose sight of the "conservative" perspective within this discourse-one that emphasizes the potential consequences of failure. While constantly addressing relapse as a looming cloud may not yield benefits for patients, overlooking these potential pitfalls could tip the balance too far, resulting in unintended harm rather than good. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Common knowledge processing patterns in networks of different systems.

Knowledge processing has patterns which can be found in biological neuron activity and artificial neural networks. The work explores whether an underlying structure exists for knowledge which crosses domains. The results show common data processing patterns in biological systems and human-made knowledge-based systems, present examples of human-generated knowledge processing systems, such as artificial neural networks and research topic knowledge networks, and explore change of system patterns over time. The work analyzes nature-based systems, which are animal connectomes, and observes neuron circuitry of knowledge processing based on complexity of the knowledge processing system. The variety of domains and similarity in processing mechanisms raise the question: if it is common in natural and artificial systems to see this pattern-based knowledge processing, how unique is knowledge processing in humans.

Multiple genes encoding mitochondrial ribosomes are downregulated in brain and blood samples of individuals with schizophrenia.

OBJECTIVES: Schizophrenia is a chronic, debilitating mental disorder whose pathophysiology is complex and not fully understood. Numerous studies suggest mitochondrial dysfunction may contribute to the development of schizophrenia. While mitochondrial ribosomes (mitoribosomes) are essential for proper mitochondrial functioning, their gene expression levels have not been studied yet in schizophrenia. METHODS: We performed a systematic meta-analysis of the expression of 81 mitoribosomes subunits encoding genes, integrating ten brain samples datasets of patients with schizophrenia compared to healthy controls (overall 422 samples, 211 schizophrenia, and 211 controls). We also performed a meta-analysis of their expression in blood, integrating two blood sample datasets (overall 90 samples, 53 schizophrenia, and 37 controls). RESULTS: Multiple mitoribosomes subunits were significantly downregulated in brain samples (18 genes) and in blood samples (11 genes) of individuals with schizophrenia, where two showed significant downregulation in both brain and blood, MRPL4 and MRPS7. CONCLUSIONS: Our results support the accumulating evidence of impaired mitochondrial activity in schizophrenia. While further research is needed to validate mitoribosomes' role as biomarkers, this direction has the potential to promote patients' stratification and personalised treatment for schizophrenia.

Up-Regulation of S100 Gene Family in Brain Samples of a Subgroup of Individuals with Schizophrenia: Meta-analysis.

The S100 proteins family is known to affect neuroinflammation and astrocyte activation, which have been suggested to be contributors to the pathogenesis of schizophrenia. We conducted a systematic meta-analysis of S100 genes differential expression in postmortem samples of patients with schizophrenia vs. healthy controls, following the commonly used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Twelve microarray datasets met the inclusion criteria (overall 511 samples, 253 schizophrenia and 258 controls were analyzed). Nine out of 21 genes were significantly up-regulated or with tendency for up-regulation. A per-sample fold change analysis indicated that the S100 genes' up-regulation was concentrated in a subgroup of the patients. None of the genes have been found to be down-regulated. ANXA3, which encodes Annexin 3 protein and was associated with neuroinflammation, was up-regulated and positively correlated with the S100 genes' expression pattern. In addition, astrocytes and endothelial cell markers were significantly correlated with S100A8 expression. S100 correlation with ANXA3 and endothelial cell markers suggests that the up-regulation we detected reflects increased inflammation. However, it might also reflect astrocytes abundance or activation. The fact that S100 proteins were shown to be up-regulated in blood samples and other body fluids of patients with schizophrenia suggests a potential role as biomarkers, which might help disease subtyping, and the development of etiological treatments for immune dysregulation in schizophrenia.

Immune-related biomarkers and suicidal behaviors: A meta-analysis.

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogenesis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or death by suicide. The study protocol was registered with PROSPERO, CRD42020212841. Standardized mean differences (SMD) were pooled with random-effects models. Heterogeneity between studies was assessed with the I2-statistic and publication bias was evaluated by the Egger test and funnel plots. Data were based on 36 studies including 2679 persons with suicidal behaviors and 6839 comparison subjects, and four immune-related biomarkers (CRP, IL-6, TNF-α and IL-1ß). Suicidal behavior was associated with higher CRP blood levels compared with: healthy controls (SMD [95%CI] = 1.42[0.85-1.98]); patients with depression alone (SMD [95%CI] = 1.23[0.20-2.26]); and patients with any psychiatric disorders (SMD [95%CI] = 0.39[0.22-0.55]). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD [95%CI] = 1.13[0.45-1.82]) and when compared with psychiatric patients without suicidal behaviors (SMD [95%CI] = 0.22 [0.11-0.33]). Meta-regression and subgroup analyses revealed that increased CRP in suicidal behavior is primarily driven by recent suicidal behavior. These results implicate the immune system and inflammatory response in suicidal behavior independent of a relationship to major psychiatric disorders, and that these biological measures are predominantly state-dependent markers. Future studies are needed to determine the cause-and-effect relationship of these immune system biomarkers with suicidal behavior, and their potential predictive properties.

Anterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration.

Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy (1H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. 1H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P < 0.02; n = 42). Overall accuracy was greatest for ACC Glx (69%) and increased to 75% when symptom severity at baseline was included in the model. Glutamate metabolites in the caudate were not associated with response, and there was no significant change in glutamate metabolites over time in either region. These results add to the evidence linking elevations in ACC glutamate metabolites to a poor antipsychotic response. They indicate that glutamate may have utility in predicting response during early treatment of first episode psychosis. Improvements in accuracy may be made by combining glutamate measures with other response biomarkers.

Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine.

BACKGROUND: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment. METHODS: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale. RESULTS: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data. CONCLUSIONS: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.

Clinical correlates of early onset antipsychotic treatment resistance.

BACKGROUND: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. AIM: This study investigates sociodemographic and clinical correlates of early onset of TRS. METHOD: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. RESULTS: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). CONCLUSION: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Cognitive function and treatment response trajectories in first-episode schizophrenia: evidence from a prospective cohort study.

OBJECTIVES: This prospective cohort study tested for associations between baseline cognitive performance in individuals early within their first episode and antipsychotic treatment of psychosis. We hypothesised that poorer cognitive functioning at the initial assessment would be associated with poorer antipsychotic response following the subsequent 6 weeks. DESIGN: Prospective cohort . SETTING: National Health Service users with a first-episode schizophrenia diagnosis, recently starting antipsychotic medication, recruited from two UK sites (King's College London, UK and University of Manchester, UK). Participants attended three study visits following screening. PARTICIPANTS: Eighty-nine participants were recruited, with 46 included in the main analysis. Participants required to be within the first 2 years of illness onset, had received minimal antipsychotic treatment, have the capacity to provide consent, and be able to read and write in English. Participants were excluded if they met remission criteria or showed mild to no symptoms. PRIMARY AND SECONDARY OUTCOME MEASURES: Antipsychotic response was determined at 6 weeks using the Positive and Negative Syndrome Scale (PANSS), with cognitive performance assessed at each visit using the Brief Assessment of Cognition in Schizophrenia (BACS). The groups identified (responders and non-responders) from trajectory analyses, as well as from >20% PANSS criteria, were compared on baseline BACS performance. RESULTS: Trajectory analyses identified 84.78% of the sample as treatment responsive, and the remaining 15.22% as treatment non-responsive. Unadjusted and adjusted logistic regressions observed no significant relationship between baseline BACS on subscale and total performance (BACS t-score: OR=0.98, p=0.620, Cohen's d=0.218) and antipsychotic response at 6 weeks. CONCLUSIONS: This investigation identified two clear trajectories of treatment response in the first 6 weeks of antipsychotic treatment. Responder and non-responder groups did not significantly differ on performance on the BACS, suggesting that larger samples may be required or that an association between cognitive performance and antipsychotic response is not observable in the first 2 years of illness onset. TRIAL REGISTRATION NUMBER: REC: 17/NI/0209.

A predictor model of treatment resistance in schizophrenia using data from electronic health records.

OBJECTIVES: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. METHODS: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. RESULTS: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. CONCLUSIONS: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

Trends of new-onset psychosis or mania in psychiatric emergency departments during the COVID19 pandemic: a longitudinal comparative study.

COVID19 infection was associated with possible psychiatric manifestations, including psychosis and mania. In addition, psychiatric disorders might be triggered by severe psychological reactions to the pandemic or the measures taken to contain it. This study aimed to assess the trends of new-onset psychosis/mania during the pandemic timeline. Psychiatric emergency department records during January-July 2019 and 2020 of two regional mental health centers were manually examined. Cases of new-onset psychosis or mania were found in 326 out of 5161 records examined. The ratio of these cases increased by 45.5% in 2020 compared to 2019 (189 out of 2367, 137 out of 2479, respectively, p = 0.001). The peak increase was in April 2020 (9.4% vs. 4.7%, p = 0.015). There was no association between the rise of new-onset psychotic or manic episodes and national incidence of COVID19 cases, as observed during Israel 2nd wave. PCR tests were negative, except a single case. In this study, an increase in new-onset psychosis/mania was identified during the initial phase of the pandemic. Though causality could not be directly inferred, lack of infection symptoms, negative PCR testing and temporal distribution incongruent with COVID19 caseload did not support a direct effect of SARS-CoV-2. Alternative explanations are discussed, such as psychological reaction to stress and preventive measures, as well as case-shifting between different mental health settings.