Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.

Clozapine-Induced Eosinophilia: a Case Report

Introduction: Clozapine is an atypical antipsychotic drug eligible for treatment-resistant schizophrenia. It frequently represents the best and the only choice in resistant schizophrenia. However, its use is feared by many professionals due to its possible adverse effects, such as eosinophilia. Case report: We report a case of a young white male suffering from treatment-resistant schizophrenia who rapidly developed eosinophilia after starting clozapine. Discussion: We present a case of a 26-year-old white man diagnosed with schizophrenia with poor clinical response to several antipsychotics owing to which clozapine was started. Psychotic symptoms improved dramatically but a progressively ascendant eosinophilia was reported during serial haematological analyses. The patient remained physically asymptomatic. An exhaustive assessment with ancillary diagnostic tests revealed no cause for eosinophilia. Thus, a diagnosis of clozapine-induced eosinophilia was made. The drug was discontinued and eosinophil count progressively returned to normal but psychotic symptoms worsened. Conclusions: Clozapine treatment is frequently feared due to its possible side effects and complications, delaying its use in refractory schizophrenia. Also, to our knowledge, there are no specific guidelines on how to manage haematological side effects such as eosinophilia. This is problematic as, in some cases, it may lead to an unnecessary withdrawal of clozapine with a worsening of psychotic symptoms. We present a brief discussion of the recent literature on the subject.

Introducción: La clozapina es un fármaco antipsicótico atípico eligible para la esquizofrenia resistente al tratamiento. Con frecuencia representa la mejor y la única opción para la esquizofrenia resistente. Sin embargo, muchos profesionales temen utilizarla por sus posibles efectos adversos, como la eosinofilia. Reporte de caso: Se expone el caso de un joven blanco que sufre esquizofrenia resistente al tratamiento y desarrolló eosinofilia rápidamente tras comenzar el tratamiento con clozapina. Discusión: Varón de 26 años con diagnóstico de esquizofrenia y mala respuesta clínica a varios antipsicóticos, por lo que se inició clozapina. Los síntomas psicóticos mejoraron drásticamente, pero los análisis hematológicos seriados informaron una eosinofilia en ascenso progresivo. El paciente permaneció físicamente asintomático. Una evaluación exhaustiva con pruebas de diagnóstico complementarias no reveló ninguna causa de eosinofilia. Por lo tanto, se diagnosticó eosinofilia inducida por clozapina. Se suspendió el fármaco, el recuento de eosinófilos volvió progresivamente a la normalidad, pero los síntomas psicóticos empeoraron. Conclusiones: A menudo se teme tratar con clozapina por sus posibles efectos secundarios y sus complicaciones, lo cual retrasa su uso en la esquizofrenia refractaria. Además, hasta donde sabemos, no existen pautas específicas sobre cómo tratar los efectos secundarios hematológicos como la eosinofilia. Esto es problemático porque, en algunos casos, puede conducir a suspender innecesariamente la clozapina y que empeoren los síntomas psicóticos. Se presenta una breve discusión de la literatura reciente sobre el tema.

Guía práctica para el uso de clozapina en niños/as y adolescentes / Practical guidelines for the use of clozapine in children and adolescents

El uso de clozapina (CZP) en niños/as y adolescentes ha estado históricamente limitado, debido a los efectos adversos y riesgos médicos asociados al fármaco, a pesar de ser una herramienta farmacológica de gran efectividad en la psiquiatría general. A continuación, se presenta una guía clínica con los siguientes objetivos: 1) identificar los criterios de indicación de CZP en niños, niñas y adolescentes (NNA) según la evidencia disponible; 2) entregar algunas directrices a los clínicos y profesionales de salud respecto a la prescripción de CZP y precauciones a tener en consideración en esta población y; 3) entregar algunos datos comparativos del uso de CZP entre población infantojuvenil y población adulta. Todo lo anterior tiene como finalidad poder entregar la información necesaria para que los clínicos no limiten el uso de este fármaco y puedan prescribirlo de acuerdo con la evidencia científica disponible.

The use of clozapine (CZP) in children and adolescents has historically been limited due to the adverse effects and medical risks commonly associated with the drug, despite being a highly effective pharmacological tool in general psychiatry. Below we developed a clinical guideline with the following objectives: 1) identify the indication criteria for CZP in children and adolescents (NNA) according to the available evidence; 2) provide some guidelines to clinicians and health professionals regarding the prescription of CZP and precautions to be taken into account in this population and; 3) provide some comparative data on the use of CZP between the pediatric and adult population. The purpose of the guideline is to provide the necessary information so that clinicians do not limit the use of CLZ when needed and can prescribe it safely and according to the available scientific evidence.

Monitoring results and influencing factors of clozapine plasma concentration in patients with mental disorders / 中国医师杂志

Objective:To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration, so as to provide reference for individualized treatment.Methods:Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory (TDM) of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021, and information such as patient gender, age, body mass index (BMI), smoking history, clozapine dose, combined drug use and blood concentration monitoring results were collected; Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results:Among 221 monitoring reports, 74 cases (normal concentration group) had clozapine plasma concentration within the effective plasma concentration range (350-600 ng/ml), 103 cases (low concentration group) were lower than the effective plasma concentration range (<350 ng/ml), and 44 cases (high concentration group) were higher than the effective plasma concentration range (>600 ng/ml). The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine, standard dose, smoking history, course of disease, and abnormal liver function of patients in different blood concentration groups of clozapine (all P<0.05). The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate, amisulpride, aripiprazole and lithium carbonate in turn. The proportion of clozapine combined with ≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and ≥ two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration (350-600 ng/ml), and the combination of two drugs was more beneficial [ OR(95% CI): 1.795(0.753-4.282)], with a statistically significant difference ( P<0.05). Conclusions:Clozapine plasma concentration varies greatly among individuals, and the therapeutic window is narrow. It is necessary to adjust the dosage in combination with the basic information and clinical information of patients, and regularly monitor the plasma concentration, so as to achieve the safety and effectiveness of individualized drug use.

A bioequivalence study of generic and brand clozapine in schizophrenic patients / 中国临床药理学与治疗学

AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril

Effects of long-term oral administration of antipsychotic clozapine on the ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effects of long-term use of clozapine on tear film stability and ocular surface tissue structure.METHODS: Case-control study was conducted on 45 patients(group 1)who were diagnosed with schizophrenia and treated with clozapine for 3.45±0.72a between March 2021 and December 2021. Another 45 healthy subjects(group 2)served as controls, whose demographic characteristics were similar to those of group 1. Patients' dry eye symptoms were investigated using OSDI questionnaire, tear secretion was detected by the Schirmer I test, ocular surface damage was assessed by the ocular surface staining score, and comprehensive ophthalmic examination was performed on all patients through LipiView ocular surface interferometer, ocular surface integrated analyzer, corneal confocal microscope and slit lamp photographic system.RESULTS: Slit-lamp photography showed diffuse grayish-white spot-like opacification in the corneal stroma of group 1, accompanied by brown star-like opacification in the center of the anterior capsule of the lens. OSDI scores were 38.00(31.50, 48.50)and 15.00(9.00, 19.50)in the two groups respectively. Schirmer test showed that the group 1 was 5.27±2.18mm/5min, while group 2 was 15.62±3.05mm/5min. Corneal fluorescein staining score: 4.00(2.50, 5.00)for group 1 and 1.00(0.00, 1.50)for group 2. The lissamine green staining score for the conjunctiva was 9.00(6.50, 10.00)and 3.00(2.00, 3.50)for the two groups, respectively. LipiView detected lipid layer thickness(LLT), suggesting that the results of group 1 and group 2 were similar, respectively 75.91±15.51 and 77.24±12.11nm; and the results were similar for the lid gland deficiency score, with 1.37±0.26 and 1.29±0.31 points, respectively. The mean tear meniscus height in group 1 was 0.13±0.06mm, which was lower than 0.23±0.04mm of group 2. Non-invasive breakup time(NIBUT)was 6.04±2.62 and 11.4±2.74s in group 1 and group 2 respectively. OSDI score, Schirmer Ⅰ test, ocular surface staining score, tear meniscus height and NIBUT were significantly different between the two groups(P&#x003C;0.05). Confocal corneal microscopy suggested decreased corneal nerve fiber density with stromal layer inflammatory cell infiltration and pigmentation in group 1.CONCLUSION: The antipsychotic drug clozapine can induce dry eye with a range of ocular surface injuries such as corneal pigmentation, and patients who taking such drugs should be routinely examined by an ophthalmologist.

Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Abstract Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 µM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 µM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 µM) and CLO (0.01 and 1 µM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 µM. HAL and CLO present cytotoxicity at 0.1 µM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Perceived Awareness of Clozapine associated with Socio- Demographic status, clinical, and side effect profile among patients from Mental Health Hospital, Taif, Saudi Arabia

Background: The main objective was to investigate the Socio-demographic, clinical, and side effect profile of patients on clozapine from Mental Health Hospital, Taif, Saudi Arabia. This article reports on an observational study. Clozapine is a second-generation atypical antipsychotic used as the drug of choice for the treatment resistant psychosis. It is supposed to be a baseline study from which we will get and understand rate of clinical, and side effect profile of the clozapine taking patients. Physicians, particularly psychiatrists are not only ignoring but also not aware, alert, so they always need to be watchful to the fatality of the drug, and take appropriate therapeutic measures. The aim was to study the socio-demographic status, clinical profile, comorbidity, side effects and outcome of patients treated with clozapine. Methodology: We reviewed all the indoor psychiatric patients of Mental Health Hospital, Taif, Saudi Arabia, from the period of one year between January 2021 to January 2022 (N=29). Our study design focused on prospective and observational studies. Descriptive statistical analysis was explored, and presented as frequencies, and percentages. We also determined crude rates for all adverse outcomes of clozapine. Results: We did a nearly mean follow-up of one year. The majority of patients were male (n=26; 89.65%), with a maximum being unmarried (n=16; 55.17%). Most patients belong to nuclear families due to cultural restrictions in this country (n=23; 79.31%). Among the literacy rate illiterate were (n=2; 6.89%, and unemployed (n=23; 79.31%). Among the study populations, the majority of respondents were found to have treatment-resistant schizophrenia (n=18; 62.06%), and around 79.31% of patients took more than two antipsychotics in adequate doses. Among side effect profiles most of the patients suffered hyper-salivation (n=19; 65.51%), sedation (n=12; 41.37%), and rarely suffered from agranulocytosis. Conclusion: Socio-demographic, clinical, and side effect profiles were the significant indicators of clozapine. Clozapine has been used for treatment-resistant psychosis, but due to fatal side effect profile we used it cautiously. In our study, we found that myocarditis, hematemesis, and leukocytosis, and neutropenia are fatal side effects of clozapine. We also found hyponatremia-induced seizure. The prevalence of blood dyscrasias in our study is rarely seen. Hyper-salivation is the most common side effect reported. Majority of the patients in our study were male, and treatment resistant Schizophrenia was the most common diagnosis. Myocarditis is life-threatening side effect seen in our study

Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Risk of neutropenia among clozapine users and non-users: results from 5,847 patients

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Oculogyric crisis caused by clozapine： a case report / 四川精神卫生

This paper reported a case of a 14-year-old female patient with schizophrenia of more than 2 years who had poor efficacy on atypical antipsychotics such as aripiprazole， risperidone and olanzapine， and who developed acute dystonia adverse effects during administration. Subsequently， the treatment was changed to clozapine therapy， and during this treatment， the patient's psychotic symptoms improved， but developed salivation and adverse effects such as clozapine-induced oculogyric crisis， slurred speech and dysphagia. This paper discussed this case with a view to providing a reference for clinicians in the recognition and management of oculogyric crisis caused by clozapine.

Pharmaceutical care for patient with schizophrenia combined with pulmonary tuberculosis： a case report / 四川精神卫生

This paper reported a case of schizophrenia combined with pulmonary tuberculosis treated with clozapine in combination with rifampicin. Due to the induction of hepatic drug enzyme of rifampicin， plasma concentration of clozapine could not reach the effective concentration and the patient still had psychotic symptoms such as persecutory delusion. After discontinuation of rifampicin， plasma concentration of clozapine were in the effective concentration range and the patient's psychiatric symptoms improved. By analysing the therapeutic regimen for the patient with schizophrenia combined with pulmonary tuberculosis， this case suggested a possible interaction between clozapine and rifampin， and provided a reference for the treatment of this type of patients.

Optimization of process parameters of 3D printed clozapine dispersive tablets and establishment of personalized dose model / 药学学报

This study aims to establish the design space of the key processes for drop-on-powder 3D printing based on design of experiment (DoE). By utilizing Minitab, an experimental scheme with three factors, two levels and three center points was designed to analyze the factors that significantly affected the tablet quality attributes. Furthermore, the factor interactions were analyzed using Minitab. subsequently, the computer aided drafting (CAD) software was used to adjust the model volume with fixed radius/height ratio (r/h = 1.25) and establish a linear regression equation between model volume and dose. As a result, the drug dose could be controlled in a flexible manner. The finally determined process parameters were: ink-jet level is 12, layer thickness is 150 μm, and the X-axis printing head speed of 635 mm·s-1. Regression equation between drug content (y) and model volume (x) was y = 0.062 x - 0.582 7 (R2 = 0.999 9) showing good linear relationship. This indicated that robust and feasible process parameters were obtained through DoE, and the preparation of personalized-dose tablets was realized with good reproducibility.

General considerations for bioequivalence studies with pharmacokinetic methods for anti-schizophrenic drugs / 中国临床药理学与治疗学

On account of the characteristics of anti-schizophrenic drugs, combined with the technical guidelines for bioequivalence studies of anti-schizophrenic generic drugs in different regulatory institutions at home and abroad, taking some drugs as examples, this paper discusses the key points to be considered in carrying out bioequivalence studies from the perspective of experimental design, so as to provide certain reference for the research and development and evaluation of related products.

Treatment progress of weight gain and abnormal lipid metabolism in patients with schizophrenia caused by clozapine and olanzapine / 四川精神卫生

To address the issue of weight gain and abnormal lipid metabolism caused by clozapine and olanzapine administration in patients with schizophrenia， a qualitative and systematic review was carried out， thus providing references for clinical treatment and future research. This review embraces the aspects of pharmacotherapy， traditional Chinese medicine treatment and so on.

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS. (AU)

Agranulocitosis inducida por clozapina / Clozapine-induced agranulocytosis

RESUMEN Clozapina, actualmente, sigue siendo el gold standard para la esquizofrenia resistente al tratamiento, pero solo bajo un adecuado monitoreo hematológico, porque está asociada a agranulocitosis. Clozapina se metaboliza produciendo N-desmetilclozapina (farmacológicamente activa), el N-óxido de clozapina (inactivo) y especies reactivas de oxígeno (ion nitrenio). El recuento de neutrófilos <1000 células/mm3 corresponde a un estado de neutropenia. La agranulocitosis es un estado grave de neutropenia con un recuento absoluto de neutrófilos <500 células/mm3. Clozapina se asocia con la agranulocitosis en aproximadamente el 0,8 % de los pacientes, y el riesgo aumenta con la edad y en mujeres. Existen dos mecanismos que explican la agranulocitosis inducida por clozapina: inmunológico (respuesta mediada por el sistema inmunitario contra neutrófilos haptenizados) y tóxico (por acción de los metabolitos N-desmetilclozapina y ion nitrenio). La farmacogenética es una herramienta valiosa para conseguir la referida medicina personalizada, al adaptar e individualizar el tratamiento basado en los marcadores genéticos de cada paciente. Numerosos estudios han demostrado una asociación potencial de la agranulocitosis inducida por clozapina con ciertos haplotipos HLA (HLA-B38, DR4, DQw3, DQB1). Luego que un paciente ha presentado agranulocitosis, se conocen tres mecanismos de reexposición a clozapina: simple, con litio y con factores estimuladores de colonias de granulocitos. Debido al riesgo de agranulocitosis, las formulaciones de clozapina están disponibles solo a través de una distribución controlada, con un registro detallado de los pacientes y con una farmacovigilancia sistematizada y obligatoria.

ABSTRACT Clozapine currently remains the gold standard for treatment-resistant schizophrenia, but only under an adequate hematological monitoring, because it is associated with agranulocytosis. Clozapine is metabolized to produce pharmacologically active N-desmethylclozapine, inactive clozapine N-oxide and reactive oxygen species (nitrenium ion). A neutrophil count < 1000 cells/mm3 corresponds to a state of neutropenia. Agranulocytosis is a severe state of neutropenia with an absolute neutrophil count < 500 cells/mm3. Clozapine is associated with agranulocytosis in approximately 0.8 % of the patients, with an increased risk in older people and women. There are two mechanisms that explain the clozapine- induced agranulocytosis: immunological (response mediated by the immune system against haptenized neutrophils) and toxic (by the action of the metabolites N-desmethylclozapine and nitrenium ion). Pharmacogenetics represents a valuable tool to achieve the so-called personalized medicine by adapting and individualizing the treatment based on the genetic markers of each patient. Several studies have shown a potential association of clozapine-induced agranulocytosis with certain HLA haplotypes (HLA-B38, DR4, DQw3 and DQB1). After a patient has presented agranulocytosis, three mechanisms of clozapine rechallenge are known: simple, with lithium and with factors that stimulate granulocyte colonies. Due to the risk of agranulocytosis, clozapine formulations are available only through a controlled distribution, with a detailed record of the patients, and with a mandatory and systematized pharmacovigilance.

Esquizofrenia resistente: Definiciones e Implicancias del concepto de Esquizofrenia Resistente a tratamiento / Treatment resistant schizophrenia: definitions and implications of the Treatment Resistant Schizophrenia concept

Resumen La esquizofrenia (EQZ) es una entidad clínica altamente heterogénea. Determina un severo impacto en la calidad de vida de los pacientes y un alto costo para la sociedad. Los antipsicóticos son la primera línea de tratamiento, sin embargo, hasta un tercio de los pacientes presentaran una esquizofrenia resistente a tratamiento (ERT). Se ha propuesto que la ERT podría corresponder a un grupo neurobiológicamente distinto de la enfermedad con una arquitectura genética particular y no solo al extremo del espectro de severidad de la misma. A pesar de ello, actualmente no existe consenso en la literatura en torno a la definición de ERT. En este trabajo presentamos una revisión de diferentes definiciones de ERT centrándonos principalmente en las guías clínicas publicadas. Además se discuten las alternativas terapéuticas en ERT y, finalmente, se proponen perspectivas futuras en torno a la necesidad de desarrollar predictores de respuesta a antipsicóticos de primera y segunda línea, así como también la posibilidad de comprender la neurobiología de la ERT.

Schizophrenia (SZ) is a highly heterogeneous clinical entity. It causes a severe disruption in quality of life, and it imposes a significant burden to society. Antipsychotics are the first line treatment, however up to a 30% of the patients will present resistance to treatment. Treatment resistant schizophrenia (TRS) could be a neurobiologically distinct disorder and not merely an extremely severe form of SZ. However, there is no consensus in the literature as to the definition of TRS. In the present work we review different definitions of TRS, mainly from clinical guidelines. Furthermore, we discuss therapeutic alternatives for TRS and suggest future perspectives regarding the identification of response predictors and understanding the neurobiology of TRS.

Rapid-onset supraventricular tachycardia following clozapine initiation and its management with verapamil: a case report

Clozapine is the drug of choice for treatment-resistant schizophrenia. However, the use of clozapine is limited by its serious adverse effects, which often underlie its discontinuation. The cardiovascular side effects that raise safety concerns include tachycardia, myocarditis and cardiomyopathy. The development of clozapine-induced tachycardia is usually observed on higher dosage especially at early stages of treatment. Here, author presented the case of a patient with treatment-resistant schizophrenia who developed asymptotic supraventricular tachycardia despite low dose of clozapine at the second day of treatment. Additionally, author explored the possibility of clozapine re-challenge in combination with verapamil treatment.

Correlation analysis of serum clozapine concentration with serum homocysteine level in schizophrenic patients / 中国神经精神疾病杂志

Objective To analysis the correlation of serum clozapine concentration with serum homocysteine (Hcy) level and biochemical index in schizophrenic patients. Methods Two hundred and forty one schizophrenic patients treated with clozapine in Beijing Anding Hospital from January 1st 2017 to January 31st 2018 were enrolled in the study. Serum clozapine concentration, Hcy levels and biochemical index were measured. Patients were divided into high concentration group (n=41), normal concentration group (n=86) and low concentration group (n=114) according to serum clozapine concentration. The correlation of serum clozapine concentration with Hcy level and biochemical index was analyzed. Results The levels of Hcy, TG and LDL were higher in high clozazapine concentration group than in low concentration group and in normal concentration group (P<0.05). There was no significant difference between normal group and low concentration group in Hcy, TG and LDL levels (P>0.05). High serum clozapine concentration was positively correlated with serum Hcy (r=0.221, P=0.013), TG (r=0.193, P=0.003) and LDL level (r=0.148, P=0.021). Conclusion Serum levels of Hcy, TG and LDL in schizophrenic patients treated with clozapine are correlated with drug concentration, suggesting that patients with abnormally elevated levels of Hcy, TG and LDL should be monitored.