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Silvia Moga,1,2 Andreea Teodorescu,1,2 Petru Ifteni,1,2 Paula-Simina Petric,1,2 Ana-Aliana Miron1,2 1Transilvania University of Brasov, Brasov, Romania; 2Spitalul Clinic de Psihiatrie si Neurologie Brasov, Brasov, RomaniaCorrespondence: Petru Ifteni, Transilvania University of Brasov, Brasov, Romania, Tel +40 (724) 993329, Email petru_ifteni@yahoo.com Paula-Simina Petric, Spitalul Clinic de Psihiatrie si Neurologie Brasov, Brasov, Romania, Tel +40 (747) 629883, Email paula_petric@yahoo.comBackground: Clozapine (CLZ) is used for treatment-resistant schizophrenia (TRS). Adverse reactions to clozapine include neutropenia. In March 2020, WHO declared the COVID-19 pandemic and after, psychiatrists raised concerns regarding continuation of clozapine, due to multiple restrictions. We aimed to provide a study on the association between neutropenia and clozapine in patients with schizophrenia and COVID-19.Aim: To assess the neutrophil count in patients with schizophrenia treated with clozapine and infected with COVID-19.Methods: The study patients with schizophrenia, according to DSM-5, admitted to the Clinical Hospital of Psychiatry and Neurology Brasov, Romania, between April 2020 and October 2021. The inclusion criteria included positive RT-PCR (real-time PCR) test for COVID-19 and treatment with clozapine. We assessed three values of ANC (absolute neutrophil count): before COVID-19 infection (last ANC obtained at mandatory check), during infection and 1 month after resolution (first negative PCR test).Results: Of the 105 cases, 95 did not have neutropenia. Fifty-nine patients were males (62.1%), mean age was 43.5 years (SD = 12.1) with an average of clozapine treatment of 52.4 months (SD = 11.9). At baseline, they had a small reduction in the ANC mean value (4.41 × 109/l; SD = 2.22) which did not constitute a statistically significant decline from the prior to COVID-19 mean value of 4.66 × 109/l (SD = 2.34; p = 0.45). Values were also normal in the first month after negative PCR testing (4.45 × 109/l; SD = 2.35; p = 0.91). A total of 10 patients (9.5%) had neutropenia. The age, dose of clozapine and duration of treatment were not statistically different compared to the group without neutropenia.Conclusion: Psychiatrists and other health professionals should keep in mind that neutrophil count may decrease during COVID-19 infection in patients taking clozapine and in some cases, neutropenia may even occur. We assumed that neutropenia could be caused by COVID-19 and clozapine interaction.Keywords: clozapine, SARS-CoV-2, schizophrenia, agranulocytosis, neutropenia

Silvia Moga, Andreea Teodorescu, Petru Ifteni, Claudia Gavris, Paula-Simina Petric Faculty of Medicine, Transilvania University of Brasov, Brasov, RomaniaCorrespondence: Petru IfteniFaculty of Medicine, Transilvania University of Brasov, Romania, 29th Eroilor Boulevard, Brasov, 500036, RomaniaTel +40 724 993329Email petru_ifteni@yahoo.comBackground: Schizophrenia patients are a population at particular risk of poor outcomes in COVID-19 infection. They have multiple comorbidities that have been identified as risk factors for severe COVID-19: diabetes, hypertension, chronic obstructive respiratory disease, and end-stage renal disease.Aim: The aim of this research was to evaluate the inflammatory response and in-hospital mortality in schizophrenia patients compared to a control group without mental illness.Methods: A total of 101 consecutive individuals with schizophrenia tested positive for COVID-19 was compared with 101 individuals without schizophrenia admitted in the same hospital. The number of severe cases and the number of deaths caused by SARS-CoV-2 were evaluated between April 2020 and April 2021.Results: There were no deaths in the group of patients with schizophrenia. Although the group had a higher number of cases with pulmonary and metabolic comorbidities, in the group with SCZ there were fewer severe cases compared to the control group. The values of some markers of inflammation (CRP and fibrinogen) were significantly lower in SCZ patients. The duration from infection to diagnosis and the start of symptomatic treatment was shorter for the group with SCZ (4.2± 3.2 vs 5.3± 4.6, p < 0.05).Conclusion: The main findings of the study were that vulnerable schizophrenia individuals on antipsychotic treatment showed a lower risk of SARS-CoV-2 severe infection and a likely better COVID-19 prognosis in a protective environment. Rapid access to specialists in case of need are factors that have determined the favorable evolution in a group considered high risk. It could be speculated that antipsychotics could play an important role in preventing SARS-CoV-2 severe manifestation and may exert protective effects against detrimental courses of COVID-19.Keywords: schizophrenia, COVID-19, inflammation, antipsychotics

Antipsychotic medications are essential for managing severe mental illnesses like schizophrenia, which impacts about 1% of the global population. Despite efficacy, in some cases, they can induce hyperprolactinemia, affecting roughly half of the patients. The prevalence of this condition varies with the specific medication used. Although prolactinomas are rare among schizophrenia patients, treating them with dopamine agonists poses conflicts with antipsychotic medication, necessitating careful monitoring and adjustments. The aim of this study was to explore the presence of brain tumors, prolactinomas, and other structural brain changes in schizophrenia patients treated with second-generation antipsychotics using cerebral computed tomography (CT) scans. We conducted a cross-sectional study involving 152 hospitalized patients diagnosed between 1 January 2020 and 31 March 2024. Evaluations included cerebral CT scans, prolactin level assessments, and the monitoring of side effects. Patients, with an average age of 42.79 years and an illness duration of 17.89 years, predominantly received olanzapine (46.05%) and risperidone (36.84%). Side effects, reported by 61.78% of patients, included tremors, dizziness, and weight gain. Abnormal prolactin levels were observed in 53.95% of patients, more prevalent in females on risperidone and in both genders on olanzapine. No prolactinomas were detected on CT scans. Managing hyperprolactinemia in schizophrenia patients undergoing antipsychotic therapy is essential to prevent long-term complications and to ensure treatment compliance.

Background: Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes., Study Question: Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs)., Study Design: We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS)., Measures and Outcomes: The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment., Results: Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes., Conclusions: The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives : Neuroimaging reveals a link between psychiatric conditions and brain structural-functional changes, prompting a paradigm shift in viewing schizophrenia as a neurodevelopmental disorder. This study aims to identify and compare structural brain changes found during the first schizophrenia episode with those found after more than 5 years of illness. Materials and Methods : This prospective study involved 149 participants enrolled between 1 January 2019 and 31 December 2021. The participants were categorized into three groups: the first comprises 51 individuals with an initial psychotic episode, the second consists of 49 patients diagnosed with schizophrenia for over 5 years, and a control group comprising 50 individuals without a diagnosis of schizophrenia or any other psychotic disorder. All participants underwent brain CT examinations. Results : The study examined all three groups: first-episode schizophrenia (FES), schizophrenia (SCZ), and the control group. The FES group had a mean age of 26.35 years and a mean duration of illness of 1.2 years. The SCZ group, with a mean age of 40.08 years, had been diagnosed with schizophrenia for an average of 15.12 years. The control group, with a mean age of 34.60 years, had no schizophrenia diagnosis. Structural measurements revealed widening of frontal horns and lateral ventricles in the SCZ group compared to FES and the FES group compared to the control group. Differences in the dimensions of the third ventricle were noted between SCZ and FES, while no distinction was observed between FES and the control group. The fourth ventricle had similar measurements in FES and SCZ groups, both exceeding those of the control group. Our results showed higher densities in the frontal lobe in schizophrenia patients compared to FES and the control group, with the control group consistently displaying the lowest densities. Conclusions : In summary, our comparative imaging analysis of schizophrenia patients, first-episode schizophrenia, and control patients revealed distinct ventricular patterns, with SCZ showing greater widening than FES and FES wider than the control group. Frontal lobe density, assessed via cerebral CT scans, indicated a higher density in the SCZ group in both anterior and posterior cortex portions compared to FES and the control group, while the left posterior cortex in FES had the highest density. These findings highlight unique neuroanatomical features across groups, shedding light on structural differences associated with different stages of schizophrenia.

Background: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 (COVID-19). Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients., Study Question: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters., Study Design: We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics., Measures and Outcomes: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine., Results: This study included 100 patients. White blood cell count changes were limited to a few cases of mild granulocytopenia (8.16% in the clozapine group and 3.92% in the nonclozapine group, P = 0.37) with no cases of severe granulocytopenia or agranulocytosis., Conclusions: As far as leukocyte counts are concerned, mRNA COVID-19 vaccination seems to be safe in patients treated with clozapine who previously had SARS-CoV-2 infection. Leukocyte changes had no clinical implications., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends.

Long acting injectable antipsychotics (LAIs) are considered the ideal treatment for schizophrenia, especially for young patients with high rates of non-adherence. In the current COVID-19 pandemic, it has been reported that the administration of LAIs decreased in some areas. The aim of this study was to evaluate the impact of COVID-19 pandemic on the initiation of LAIs. This is a retrospective mirror- image study covering a total period of 24 months: 12 months before and 12 months after the declaration of COVID-19 pandemic on March 11, 2020. During the study period, out of 218 patients admitted with schizophrenia, only 15 (1.3%) received LAIs at discharge. There was a 48.3% reduction in LAIs initiation compared to the pre-pandemic period (29 LAIs initiations in 2019 from 224 admissions). Despite the 27% reduction in the total number of admissions (1500 in 2019 vs. 1100 in 2020), the number of admissions with schizophrenia remained almost the same (224 in 2019 vs. 218 in 2020). COVID-19 pandemic brought an important challenge in the treatment of patients with schizophrenia, especially in the initiation of LAIs. This could have an important impact on the relapse rate in the next period.

Schizophrenia is a psychiatric condition with chronic evolution, one of the most disabling diseases. The main cause for the disease's progression is considered to be the lack of compliance with the treatment. Long-acting injectable antipsychotics (LAIs) are an important treatment option for patients with schizophrenia. Olanzapine long-acting injection (OLZ-LAI) is a pamoate monohydrate salt of olanzapine that is administered by deep intramuscular gluteal injection. The aim of this paper is to report the effects of a sudden and unplanned switch from olanzapine long-acting injectable to oral olanzapine in remitted patients with schizophrenia due to restrictions caused by the COVID-19 pandemic. An observational study conducted in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania between April 2020 and March 2021. 27 patients with OLZ-LAI were entered into the study. Of 27 cases, 21 patients preferred to be switched to oral olanzapine (77.77%). Only 6 patients continued with the long-acting formulation. The main reason for the initiation of olanzapine pamoate in all the patients was non-adherence to oral medication (80.95%), and the mean age of starting LAI olanzapine was 36.42 years (SD ± 10.09). Within the following 12 months after switching from olanzapine LAI to OA, 15 patients (71.42%) relapsed, and 12 were admitted to the emergency psychiatric unit. The COVID-19 pandemic has brought multiple disservices to current medical practice. Sudden and unplanned switch from olanzapine long-acting formulation to oral olanzapine was followed by the high rate of relapse in remitted schizophrenia., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Schizophrenia is a severe psychiatric condition with devastating consequences for the individual's functionality and leading to severe disability. Lack of insight and non-adherence to treatment remain the most important factors in the progression of the disease to chronicity. Despite their proven effectiveness in preventing relapses, reducing morbidity and mortality, long-acting injectable antipsychotics (LAIs) are still underused. One of the causes invoked is the lack of guidelines or protocols for initiating LAIs. Objective: The aim of this article is to present Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN), a clinician-rated index that rates the important factors of the disorder across seven items: age, duration of illness, relapses, antipsychotic treatment response, family support, antipsychotic existing formulation and adherence. Method: A retrospective study in which all patients with schizophrenia discharged on oral antipsychotics without LAIs treatment lifetime were evaluated with ROLIN for opportunity for LAIs initiation. Results: Of 225 consecutive patients, 126 patients (56%) had a strong indication for initiating LAI (score between 25 and 35). Kolmogorov-Smirnov test was used for checking the normal distribution of values (95% CI for the mean = 9.5781 to 20.4219; 95% CI for the median = 6.5920 to 24.8161; SD = 9.7907; Coefficient of Skewness = 0.0743; Coefficient of Kurtosis = -1.1377). Conclusion: This paper proposed an instrument designed to improve treatment in schizophrenia using a simple conceptual model which integrates important predictors of good or poor outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ifteni, Petric and Teodorescu.)