Clozapine Group Research Articles

Local and Remote Chemogenetic Suppression of Hippocampal Seizures in Rats.

Innovative treatments of refractory epilepsy are widely desired, for which chemogenetic technology can provide region- and cell-type-specific modulation with relative noninvasiveness. We aimed to explore the specific applications of chemogenetics for locally and remotely networks controlling hippocampal seizures. A virus coding for a modified human Gi-coupled M4 muscarinic receptor (hM4Di) on pyramidal cells was injected into either the right hippocampal CA3 or the bilateral anterior nucleus of the thalamus (ANT) in rats. After one month, seizures were induced by 4-aminopyridine (4-AP) injection into the right CA3. Simultaneously, clozapine-N-oxide (CNO) (2.5 mg/kg) or clozapine (0.1 mg/kg), the specific ligands acting on hM4Di, were injected intraperitoneally. We also set up hM4Di control and clozapine control groups to eliminate the influence of viral transfection and the ligand alone on the experimental results. For both local and remote controls, the mean seizure duration was significantly reduced upon ligand application in the experimental groups. Seizure frequency, on the other hand, only showed a significant decrease in local control, with a lower frequency in the clozapine group than in the CNO group. Both the effects of CNO and clozapine were time-dependent, and clozapine was faster than CNO in local seizure control. This study shows the potency of chemogenetics to attenuate hippocampal seizures locally or remotely by activating the transfected hM4Di receptor with CNO or clozapine. ANT is suggested as a potentially safe chemogenetic application target in the epileptic network for focal hippocampal seizures.

Effects of six antipsychotic drug treatment regimens on short-term heart rate variability in patients with schizophrenia.

Many antipsychotic drugs have cardiac side effects due to their pharmacological actions. Heart rate variability (HRV) analysis can be used as a potential indicator of cardiotoxicity in cases where a decrease in HRV occurs after the administration of antipsychotics such as clozapine. The purpose of this study was to explore the effects of 6 antipsychotic drug regimens on short-term HRV in patients with schizophrenia. Data from 164 patients with schizophrenia between January 2018 and June 2023 were retrospectively analysed. Based on the drug used for treatment, the patients were categorised into clozapine combination (clozapine combined with aripiprazole, risperidone or ziprasidone), clozapine alone, olanzapine, aripiprazole, ziprasidone or risperidone groups. Heart rate variability indices were calculated using time domain analysis, including the standard deviation of the RR intervals (SDNN), the root mean square of successive RR interval differences (RMSSD) and the percentage of successive RR intervals over 50ms (PNN50). Compared with the pretreatment period, the SDNN, RMSSD and PNN50 were significantly lower in the clozapine combination, clozapine, olanzapine and aripiprazole groups at the end of weeks 2 and 4 of treatment (P < 0.05). However, these indicators in ziprasidone and risperidone groups did not show this significant decrease (P > 0.05). The effects of clozapine combination and clozapine on HRV were greater than for olanzapine, aripiprazole, ziprasidone or risperidone. Attention should be paid to controlling the dosage of clozapine combination and clozapine and monitoring the patient's electrocardiogram during administration.

Clozapine Safety in Pregnancy: A Clinical Study.

Pregnant women with persistent schizophrenia and related disorders may require ongoing antipsychotic treatment, including clozapine. However, the potential risks of using clozapine during pregnancy and the postnatal period remain uncertain. We conducted a nested case-control study using the National Register of Antipsychotic Medication in Pregnancy (NRAMP) database. Our study assessed pregnancy outcomes among Australian women diagnosed with schizophrenia spectrum disorder and treated with clozapine (n = 14) during the first trimester. These women were compared to 2 subgroups: those treated with quetiapine (n = 53) and those not taking any medication (n = 24) during pregnancy. We observed higher rates of miscarriage in the clozapine group compared to the quetiapine and drug-free groups. The clozapine group had a higher early pregnancy body mass index but lower overall pregnancy weight gain than the other groups. The prevalence of gestational diabetes was significantly higher in the clozapine group. The percentage of vaginal delivery was higher in the clozapine group than in the other 2 groups. Neonatal outcomes such as gestational age, and Apgar scores were similar across groups. The birth weight was lower in the clozapine group compared to the other 2 groups. This study suggests that pregnant women taking clozapine and their babies have greater adverse outcomes compared to other groups. Clozapine appears to be associated with a greater risk of miscarriages, maternal gestational diabetes, and lower birth weight. However, the gestational age, Apgar scores, and admission to NICU/SCN were comparable between all groups.

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics.

It was reported that patients who contracted COVID-19 while taking clozapine exhibited a distinct hematological response. However, the absence of control groups made it difficult to attribute it to clozapine. The changes in absolute neutrophil counts (ANCs) during the 4 weeks after COVID-19 infection were compared between the two groups of patients with severe mental illnesses (SMIs) (49 patients using clozapine and 54 using other antipsychotics) using generalized additive modeling. Although the pattern of a transient drop in ANC followed by gradual recovery could be demonstrated in both groups, it was more pronounced in the clozapine group ( P = 0.00025). Nevertheless, overall ANC remained at a higher level in the clozapine group. The results suggested potential interaction between clozapine and COVID-19 at the level of hematological dynamics. However, it did not necessarily indicate that such interaction is inevitably harmful or dangerous. It was more of a concern that some patients using other antipsychotics exhibited decreased ANC, which did not easily recover. Traditionally, clinicians have been concerned about the worsening of hematological side effects in clozapine patients after COVID-19 infection. However, the obtained result highlighted the necessity of hematological monitoring in patients using any type of antipsychotics for SMIs.

Association of clozapine with structural and resting-state functional abnormalities of the hippocampus in chronic schizophrenia.

Abnormalities in the hippocampus have been extensively reported in schizophrenia research. However, inconsistent findings exist, and how structural and functional abnormalities of the hippocampus are associated with clinical symptoms in schizophrenia, especially concerning clozapine treatment, remains uncertain. We recruited 52 patients with schizophrenia, each with an illness duration of at least 5 years, and categorized them based on clozapine treatment. T1-weighted images and resting-state functional magnetic resonance imaging scans were obtained and analyzed to perform group comparisons of the structural and functional changes in the hippocampus. Volumes of the hippocampal subregions, as well as resting-state functional connectivity maps from these areas were compared between the groups. Associations with clinical symptoms, including the severity of psychiatric symptoms and cognitive functions, were investigated. The clozapine group (n=23) exhibited smaller volumes in several hippocampal subregions, including the CA1, CA4, granule cell and molecular layers of the dentate gyrus, compared to the non-clozapine group (n=29). Seven clusters with significant group differences in functional connectivity with these hippocampal subregions were identified, with six of these clusters showing increased functional connectivity in the clozapine group. The reduced volumes of the hippocampal subregions were moderately associated with the severity of negative symptoms, general intelligence, and executive function. Patients with schizophrenia undergoing clozapine treatment exhibited smaller volumes in the hippocampal subregions, which were moderately associated with negative symptoms and cognitive functions, compared to those without clozapine treatment.

Influence and Mechanism of Traditional Chinese Medicine Intervention on Cognitive Dysfunction in Patients with Schizophrenia

This study investigates the impact and mechanisms of traditional Chinese medicine (TCM) intervention in patients with schizophrenia. In animal experiments, a total of 48 rats were randomly divided into four groups: control group (CG), model group (MG), Albizia flower flavonoid group (AFFG), and clozapine group (CLG). Each group consisted of 12 rats. After treatment, MK-801 was administered to the MG, AFFG, and CLG to establish schizophrenia rat models, while the CG received physiological saline. Cognitive abilities, hippocampal pathology, and protein expression were evaluated, and the expression levels of c-fos, cleaved Caspase-3, Bcl-2, and Bax were determined. In clinical trials, the study included 82 patients with schizophrenia treated at our hospital from February 2022 to February 2023. They were divided into the observation group (OG) and the experimental group (EG), with 41 cases in each group. The EG received aripiprazole and self-formulated TCM decoction, while the OG received aripiprazole. The PANSS scores and quality of life levels were compared. The results revealed impaired cognition, altered protein expression, and increased pathology in the MG compared to the CG. The AFFG and CLG exhibited enhanced cognition, improved protein expression, and reduced pathology when compared to the MG. Clinical findings demonstrated significantly lower PANSS scores and improved quality of life in the EG compared to the OG. In conclusion, Albizia flower flavonoids effectively modulated protein expression, ameliorated cognitive dysfunction, and reduced pathology. Additionally, the decoction decoction enhanced cognition and quality of life in patients with schizophrenia, suggesting promising clinical applications.

Effect of taxifolin on clozapine-induced experimental oxidative and inflammatory heart damage in rats

AimClozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (3,5,7,3’,4’-pentahydroxy flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data. Material and methodThe rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin+clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-▪B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically. ResultsTroponin I, CK-MB, MDA, TNF-α, NF-▪B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin+clozapine groups (P<0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (P>0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin+clozapine group, while they were significantly lower than the clozapine group (P<0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin+clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin+clozapine group (TLC group), myofibrils generally showed a regular morphology. ConclusionWe found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury.

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection.

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. The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. 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. The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine. 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. 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.

Clozapine in Treatment-Resistant Schizophrenia and Its Augmentation with Electroconvulsive Therapy in Ultra-Treatment-Resistant Schizophrenia.

Clozapine is considered the gold standard for patients with treatment-resistant schizophrenia (TRS) who have previously tried other antipsychotics at adequate doses (two or more, with at least one being atypical). However, despite optimal treatment, a subgroup of TRS patients with what is known as ultra-treatment-resistant schizophrenia (UTRS) fails to respond to clozapine, which occurs in 40-70% of cases. The most common approach to manage UTRS involves augmenting clozapine with pharmacological or non-pharmacological interventions, with a growing body of evidence that supports the use of electroconvulsive therapy (ECT) as an augmenter. This prospective non-randomized 8-week study, which followed the TRIPP Working Group guidelines and is one of few that separate TRS from UTRS, aimed to evaluate the effectiveness of clozapine in TRS patients and the efficacy of ECT augmentation of clozapine in UTRS patients. Patients with TRS were assigned to receive clozapine alone (clozapine group), whereas UTRS patients received bilateral ECT in addition to their current medication regimen (ECT plus clozapine group). The severity of symptoms was evaluated using the Clinical Global Impression Scale (CGI) and Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of the 8-week trial. Both treatment approaches resulted in improved CGI and PANSS scores. The results suggest that both clozapine and ECT are effective treatment options for patients with TRS and UTRS, respectively, and that adherence to guidelines should provide a better frame for future clinical studies.

Akathisia rate among psychiatric patients treated with Clozapine compared to Risperidone.

Introduction Patients’ cooperation, especially in medication taking, constitutes a significant challenge in psychiatric care. Psychiatric patients are often reluctant to take a specific pharmacological treatment because of side effects. Akathisia and other extra pyramidal symptoms are side effects that could result into real danger and are thought to be the main reasons of discontinuing pharmacological treatment. Despite this, some gaps in research knowledge exist on the rate of psychiatric patients that suffer from Akathisia. For example, Clozapine treatment, despite its efficacy, is often disqualified due to side effects concern. The research literature barely refers to the development of extrapyramidal symptoms, and more specifically Akathisia. There are few reports about Akathisia when taking Clozapine. It results into a lack of objective studies and knowledge based only on subjective clinical evaluations.ObjectivesThis study aims at comparing Clozapine and Risperidone in general, with or without polypharmacy and more especially, in terms of Akathisia.MethodsThis research was carried out in Abarbanel Mental Health Center over a period of six months. The study population included 100 patients, including hospitalized and ambulatory patients. They were equally divided into two groups: 50 patients who received Clozapine, and 50 patients who received Risperidone. It should be noted that due to polypharmacy, 17 patients in the Clozapine group and 6 patients in the Risperidone group received additional anti-psychotic treatment. Akathisia was evaluated using Barnes Akathisia Scale (BAS).Results The demographic and clinical data was found identical in both groups. We found that Akathisia symptoms appeared 1.4 times more in patients who took Risperidone only, compared to those who took Clozapine only (p &lt; 0.05). This research emphasizes the irrelevance of existing data on anti-psychotics’ treatments, while 24% of the patients treated with Clozapine and 34% of the patients treated with Risperidone showed Akathisia symptoms.Conclusions Akathisia symptoms are very common in patients who take anti-psychotic treatment as Clozapine and Risperidone. Previous research revealed that Akathisia is very common for Risperidone patients, however the symptoms are often neglected in patients taking Clozapine. We show in our research that the rate of Akathisia is high in both treatments. Therefore, the importance of diagnosing akathisia should be emphasized in patients treated with Clozapine. Moreover, Akathisia should receive much more importance when choosing anti-psychotic treatment.Disclosure of InterestNone Declared

Long–term Neurodevelopment outcomes to Prenatal Antipsychotic Medication Exposure: Systemic Review

IntroductionPeak incidence for many psychiatric disorders occurs in reproductive years. We don’t have FDA-approved drugs or clinical guidelines. The main cause of pharmacological suspension in pregnancy is the lack of knowledge of their effects on the product. Gathering information on this regard becomes crucial so we can avoid relapses or exacerbationObjectivesDescribe neurodevelopmental effects in children ≥ 6 months exposed to antipsychotics prenatally.MethodsPROSPERO-CRD42020170314. Using MeSH terms in 5 databases, without language and time restriction, obtaining n=3932. After review and exclusion n=24 were obtained for qualitative review. (Figure 1).ResultsOf 20 case reports 4 had more ambivalence results (Table 1). In the cohort studies, exposure may cause short-term delay at 6 months but no significant difference at 12 months (Table 2).Table 2StudyNAntipsychoticMonthsConclusion using clinical evaluationImaz et al. Front. Pharmacol.2018; 9:2641RisperdalClozapine72Abnormal memory, attention/executive, hyperactivity1Clozapine32Normal2Clozapine18AbnormalNormalBurt et al. Am J Psychiatry 2010; 167:892-8971Olanzapine12,18,22,2918 months Abnormal motor 22 months normal 29 months normalKirchheiner et al. Pharmacopsych 2000; 33:78-801Olanzapine7,117 months Abnormal motor11 months NormalMendhekar et al. J Neuropsychiatry Clin Neurosci 2007; 19:21Clozapine65 years Abnormal languageTable 3StudyNAntipsychoticMonthsConclusion using clinimetry and clinical evaluationShao et al. Plos ONE, 2015; 10(4),1-963ClozapineRisperidoneOlanzapineQuetiapine6,12BSID-III 6 months Adaptive behavior score lower in clozapine group 12 months No differenceJohnson et al. Arch Gen Psychiatry2012; 69(8), 787-79422HaloperidolSGA*6INFANIB Lower scores with SGA then HaloperidolPeng et al. Psychopharmacology 2013; 228(4), 577-58476ClozapineRisperidoneSulpirideOlanzapineQuetiapine6,12BSID-III 6 months Lower socio-emotional and adaptive behavior scores12 months No differencePetersen et al. BMJ 2016; 5(6), 1-9290FGA+SGA**6More neurodevelopmental disorder that those who didn’t take antipsychotics.Image:ConclusionsMost are case reports, hence the importance of collecting this information, not ignoring it due to lack of methodological rigor. The intent is not to conclude that prenatal exposure to antipsychotics doesn’t have long-term neurodevelopmental effects, rather documenting the available evidence contributing to an informed clinical decision.Disclosure of InterestNone Declared

Electroconvulsive therapy or clozapine for adolescents with treatment-resistant schizophrenia: an explorative analysis on symptom dimensions

Objective This study sought to compare pre-intervention patient characteristics and post-intervention outcomes in a naturalistic sample of adolescent inpatients with treatment-resistant psychotic symptoms who received either electroconvulsive therapy (ECT) or clozapine. Methods Data of adolescents with schizophrenia/schizoaffective disorder receiving ECT or clozapine were retrospectively collected from two tertiary-care psychiatry-teaching university hospitals. Subscale scores of the Positive and Negative Symptom Scale (PANSS) factors were calculated according to the five-factor solution. Baseline demographics, illness characteristics, and post-intervention outcomes were compared. Results There was no significant difference between patients receiving ECT (n = 13) and clozapine (n = 66) in terms of age, sex, and the duration of hospital stay. The ECT group more commonly had higher overall illness and aggression severity. Smoking was less frequent in the clozapine group. Baseline resistance/excitement symptom severity was significantly higher in the ECT group, while positive, negative, affect, disorganisation, and total symptom scores were not. Both interventions provided a significant reduction in PANSS scores with large effect sizes. Conclusion Both ECT and clozapine yielded high effectiveness rates in adolescents with treatment-resistant schizophrenia/schizoaffective disorder. Youth receiving ECT were generally more activated than those who received clozapine.

Advancing Clozapine Use in a Community Health System.

Advancing Clozapine Use in a Community Health System.

Differing Prevalence and Correlates of Metabolic Syndromes Between Chlorpromazine and Clozapine: A 10-year Retrospective Study of a Male Chinese Cohort.

Antipsychotics are known to be associated with metabolic syndromes (MetS). Chlorpromazine (CPZ) and Clozapine (CLZ) are currently the most commonly used antipsychotics in low-income districts of China. However, potential differences in the long-term effects of CPZ and CLZ on MetS in schizophrenia inpatients are not well understood. Here, we aimed to identify any MetS profile differences between long-term schizophrenia patients who were prescribed either CPZ or CLZ at a primary psychiatric hospital. We recruited a total of 204 male schizophrenia patients who received either CPZ or CLZ. We measured their weight, height, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP), as well as their biochemical indicators, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). The MetS prevalence in the CPZ and CLZ groups was 31% and 37.5%, respectively. The CLZ group had significantly higher DBP levels and a higher incidence of dyslipidemia (HDL-c) but lower HDL-c and TC levels than the CPZ group. We also determined that smoking history, BMI, and duration of hospitalisation were risk factors for the development of MetS. Moreover, we found that CPZ and CLZ were correlated with the same risk for developing MetS and that BMI was a vital risk factor of MetS for both the CPZ and CLZ groups. Long-term CPZ and CLZ prescriptions were associated with similar profiles for developing MetS of schizophrenia patients.

Metabolic syndrome and cardiovascular risk between clozapine and non-clozapine antipsychotic users with schizophrenia.

Clozapine use is associated with higher risks of metabolic side effects and cardiovascular diseases (CVD). Thus, this study aims to establish and compare the cardiometabolic profiles between non-clozapine antipsychotic and clozapine users with schizophrenia. Data from 88 non-clozapine and 166 clozapine users were extracted from existing databases - demographics, medications, smoking and medical histories, anthropometric parameters, serum lipid and fasting glucose levels. Prevalence of metabolic syndrome (MetS) was established using the AHA/NHLBI criteria. Cardiovascular risk profiles were established using the Framingham risk score (FRS). The clozapine group had significantly higher proportions of diagnosed hypertension (10.8% vs. 3.4%, p=0.041), diabetes mellitus (15.7% vs. 3.4%, p=0.003) and dyslipidemia (36.7% vs. 12.5%, p<0.001). However, the non-clozapine antipsychotic group had poorer anthropometric, serum lipids and glucose levels. The prevalence rates of MetS in the clozapine and non-clozapine antipsychotic groups were not statistically significant at 42.8% and 43.2%, respectively. As for CVD risk, the non-clozapine antipsychotic group had significantly higher FRS (6.59% vs. 6.12%, p=0.001). Although clozapine users had higher rates of diagnosed metabolic conditions, other cardiometabolic parameters appeared better compared to non-clozapine antipsychotic users, which could be due to greater awareness, earlier detection and treatment. Regardless of the type of antipsychotic used, metabolic abnormalities are prevalent in individuals with schizophrenia; physical healthcare should be prioritised alongside mental healthcare in this group.

Influence of antipsychotics on metabolic syndrome risk in patients with schizophrenia.

ObjectiveMany studies so far have shown that antipsychotic therapy may have an effect on the development of metabolic syndrome in patients diagnosed with schizophrenia. Our goal was to determine whether our respondents are at risk for developing metabolic syndrome and who is more predisposed to it.MethodsIn a stable phase, 60 patients diagnosed with schizophrenia were equally divided into three groups according to the drug (risperidone, clozapine, and aripiprazole monotherapy). Control group had 20 healthy examinees. Patients were evaluated first using The Positive and Negative Syndrome Scale (PANSS). Prolactin, lipid status, glycemia, insulin, cytokine values (IL-33, TGF-β, and TNF-α) and C-reactive protein (CRP) were measured. Also, Body mass index (BMI), Homeostatic Model Assesment for Insulin Resistance (HOMA index), waist and hip circumference (WHR) and blood pressure (TA) measurement were performed in the study.ResultsPatients treated with risperidone compared to healthy control subjects and aripiprazol group of patients had statistically significant difference in prolactin levels. In clozapine group compared to healthy control group values of HDL cholesterol and glucose level were statistically significant different. In aripiprazole group compared to healthy control group value of BMI was statistically significant different. Statistically significant correlations were found in TNF-α with glucose and HOMA index in risperidone treated patients and with BMI in clozapine group of patients; IL-33 with glucose in risperidone and with BMI in clozapine group of patients and TGF-β with glucose in risperidone group, with insulin and HOMA index in clozapine group and statistically significant negative correlation with LDL cholesterol in aripiprazole group of patients.ConclusionPatients on risperidone and clozapine therapy may be at greater risk of developing metabolic syndrome than patients treated with aripiprazole. Statistically significant difference in concentration of TNF-α and TGF-β was in the group of patients treated with risperidone compared to healthy control group.

Naturalistic study on the use of clozapine in the early phases of non-affective psychosis: A 10-year follow-up study in the PAFIP-10 cohort

Clozapine is seldom prescribed in treatment-resistant schizophrenia (TRS) patients during early phases of the illness. We aimed to examine the pathway and patterns and the impact of clozapine use in patients with TRS who were followed up for 10 years after the first outbreak of the illness. Data were obtained retrospectively from an epidemiological cohort of first episode schizophrenia patients (n = 218) who had been treated in a specialized intervention program (PAFIP). Out of 218, 35 (16%) individuals were on clozapine at 10-year assessment, while 183 (84%) were taking other antipsychotics. Among those 183 psychosis subjects who were not on clozapine, 13 (7.1%) met criteria for TRS. In the clozapine group, ten (28.6%) met criteria for early-TR and twenty-five (71.4%) met criteria for late-TR. Before clozapine treatment was initiated, the median number of days under other antipsychotic treatment was 1551 days (IQR = 1715) and the median time that subjects remained on clozapine was 6.3 years (IC95%: 5.49–7.20). At 10 years, we found that those individuals taking clozapine had higher CGI total scores (F = 12.0, p = 0.001) and SANS total scores (F = 9.27, p = 0.003) than subjects taking other antipsychotics after correcting for baseline values. Interestingly, when performing these analyses at 10 years between subjects taking clozapine (n = 35) and subjects who despite meeting TRS criteria were not taking clozapine (n = 13), we found that subjects taking clozapine had significantly lower total scores on all clinical scales compared with subjects who met TRS criteria and were not taking clozapine (p values < 0.05). TRS patients who took the longest time to start clozapine (third tertile) showed significantly higher CGI scores at 10-year follow-up compared to those who initiated clozapine earlier (first tertile) (t = 2.60; p = 0.043). Our findings reinforce the need of a timely assessment of treatment-resistant criteria in early schizophrenia patients and highlight the long-term benefits of an early introduction of clozapine on those patients meeting treatment-resistant criteria.

Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study.

Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P &lt; 2.0 × 10-16) and the ND-TRS without clozapine group (54.7%; P &lt; 2.0 × 10-16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10-6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10-6). Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.

In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS. In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures. The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017). Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

Comparative effects of clozapine and risperidone monotherapy on levels of immunoglobulins in patients with schizophrenia – A 12 weeks' longitudinal study

Background: Schizophrenia is among the most puzzling yet disabling of all brain diseases. The finding of immunity-related genes seems to vindicate theories about the involvement of neuroimmunological processes in the pathogenesis of schizophrenia. Moreover, antipsychotics used in the treatment of schizophrenia have been shown to have effects on serum immunoglobulin levels. Aim: The aim of this study was to assess and compare the effect of risperidone and clozapine on the immunoglobulins at 6 weeks and 12 weeks in patients with schizophrenia and its clinical correlation. Materials and Methods: It was an open-label, randomized, comparative, and prospective study. Patients with International Classification of Diseases-11th Revision diagnosis of schizophrenia who were not on any antipsychotic drug for more than 2 weeks, were randomized to two groups, i.e., A (risperidone) and B (clozapine) after baseline assessment of sociodemographic and clinical parameters on the Positive and Negative Syndrome Scale (PANSS). Baseline blood investigations (complete hemogram, liver and renal function tests, lipid profile, and fasting blood sugar) and immunoglobulin estimation were done. Patients were followed at 6 weeks and 12 weeks and levels of immunoglobulin were reassessed at 6 weeks and 12 weeks along with PANSS and Glasgow Antipsychotic Side-Effect checklist. Results: A total of 32 patients were inducted into the study – 16 in the risperidone group and 16 in the clozapine group. There was no statistically significant difference in terms of the duration of illness or period of exacerbation between the two groups though the baseline total PANSS score was significantly higher in the clozapine group. In both the groups, there was no statistically significant difference in the baseline immunoglobulin levels at baseline and over 12 weeks in terms of the immunoglobulin G (IgG), IgM, and IgE levels. Within the clozapine group, a significant difference over 12 weeks was noted in IgG level. Conclusion: It can be concluded from the index study that the immunoglobulin levels in the patients with schizophrenia do not differ much concerning the effect of risperidone and clozapine. Clozapine is associated with a significant increase in IgG levels indicating the immunologic response of clozapine in schizophrenia.