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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

Andreea Teodorescu,1 Petru Ifteni,1 Ana Dragan,2 Marius Alexandru Moga,1 Ana Aliana Miron,1 Lorena Dima1 1Transilvania University of Brasov, Faculty of Medicine, Brasov, Romania; 2Clinical Hospital of Psychiatry and Neurology of Brasov, 3rd Department of Clinical Psychiatry, Brasov, RomaniaCorrespondence: Petru IfteniTransilvania University of Brasov, Faculty of Medicine, 29th Eroilor Bvd, Brasov, RomaniaTel +40724993329Email petru_ifteni@yahoo.comBackground: The postpartum period is a difficult time for mother and family. Unfortunately, in some cases, two psychiatric complications may occur: postpartum psychoses (PPP) with a prevalence of 0.2% and a very low incidence of 0.25– 0.50 per 1000 deliveries, and post-natal depressions with an incidence of 10 to 20% per 1000 deliveries. The onset of postpartum psychosis is in the first 4 weeks after childbirth with symptoms such as emotional lability, cognitive disorganization, delusional beliefs and hallucinations. It requires hospitalization due to the high risk of suicide and infanticide. The studies reveal that the treatment can include FGAs (first-generation antipsychotics), such as haloperidol, and SGAs (second-generation antipsychotics), such as olanzapine, quetiapine and risperidone. The literature is scarce in what resistant PPP is concerned and no such cases treated with clozapine have been reported, according to our knowledge. The present case report focuses on a female diagnosed with PPP who was treated with clozapine due to the lack of response to adequate dosage of 2 second-generation antipsychotics.Case Presentation: We present the case of a 30-year-old primiparous woman on her 3rd day after delivery, admitted in the psychiatric emergency unit for agitation, intrusive thoughts with a content frequently related to the infant, ideas of reference, disorganized speech, bizarre behavior, verbal stereotypes, insomnia and anxiety. Due to lack of response to adequate dosage of 2 second-generation antipsychotics, clozapine was initiated up to 250 mg/day. The symptoms remitted in the next 5 days and the patient was discharged. After discharge, at the patient’s request, clozapine was replaced by olanzapine. Visit at 1 year revealed full remission of symptoms.Conclusion: Although data is extremely limited, clozapine has been shown to be effective and safe in a severe case of treatment-resistant PPP.Keywords: postpartum psychosis, antipsychotics, clozapine, suicide, treatment-resistant

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.

Background: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19., Areas of Uncertainty: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection?, Data Sources: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis., Therapeutic Advances: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients., Results: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia., Conclusions: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Emergency psychiatry has the main role of resolving suicidal behavior and aggression. These severe psychiatric symptoms can be found in many psychiatric disorders such as schizophrenia, bipolar disorder, major depression, personality disorders, cognitive disorders, intellectual disability and substance abuse. Although indications for the use of antipsychotics are limited to a specific group of diseases, they are frequently used as rescue medication in high-risk or nonresponsive cases. Clozapine, the gold standard for TRS (treatment resistant schizophrenia) is effective in controlling aggression. The aim of the research was to identify the use of clozapine for treatment-refractory aggressive behavior in psychiatric emergency. A retrospective study based on the paper files of patients admitted between 2010 and 2019 in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania. Were included all the patients admitted as a psychiatric emergency and treated with clozapine for aggressive behavior. The hospital is an academic institution with 150 beds for acute patients, serving an area of over 600,000 inhabitants. It is the main public institution where patients with psychiatric emergencies are hospitalized. Off 19,000 patients admitted during the study period, 504 patients (2,4%) with a diagnosis other than schizophrenia or schizoaffective disorder received clozapine for aggressiveness (89.5%). The first four diagnoses identified were bipolar disorder (n = 172), intellectual disability (n = 128), cognitive impairment (n = 112), and personality disorder (n = 92). Other disorders identified but with a smaller number of cases were major depressive disorder (n = 3), adjustment disorders (n = 2), delusional disorder (n = 2), obsessive compulsive disorder (n = 2) and postpartum psychosis (n = 1). Clozapine was used as 3rd or 4th choice. The dose was greater for manic patients (350.29 ± 98.01 mg/day) compared with all the other diagnoses. Clozapine was effective and safe in cases of patients with treatment-refractory aggressive behavior.