clozapine / Generic mfg. - LARVOL DELTA

Short febrile illness with rashes and diarrhea after clozapine therapy: A case report. (PubMed, Indian J Psychiatry) - No abstract available

Journal

Clozapine Re-challenge in a Patient With Pericarditis: A Case Report. (PubMed, Cureus) - "Clozapine was successfully re-titrated without any clinical, biochemical, or radiological deterioration of pericarditis. This case highlights the safe and successful re-titration of clozapine in patients presenting with pericarditis, within weeks of initial presentation and with ongoing mild biochemical disturbances without any significant deterioration in cardiovascular status or function."

Journal • Cardiovascular • CNS Disorders • Pain • Psychiatry • Schizophrenia

Clozapine in treatment-resistant early-onset schizophrenia: A two-year follow-up retrospective observational study. (PubMed, Eur Neuropsychopharmacol) - No abstract available

Journal • Observational data • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Clozapine-induced cardiac toxicity and successful rechallenge in children and adolescents: a systematic review and new case report. (PubMed, Psychiatry Res) - "Overall, the available evidence, though limited, supports clozapine rechallenge after drug discontinuation due to cardiac toxicity in children and adolescents. Ensuring full cardiac recovery before rechallenging with clozapine, starting with a low dose (6.5-12.5 mg/d), a slow titration rate (12.5-25 mg/d per week), avoiding the co-administration of valproic acid (Depakene), and frequent monitoring of cardiac and inflammatory parameters appear critical to the success of clozapine rechallenge."

Journal • Review • Bipolar Disorder • Cardiovascular • CNS Disorders • Inflammation • Mood Disorders • Pediatrics • Psychiatry • Schizophrenia

Shared and unique therapeutic targets of KarXT and clozapine for schizophrenia treatment revealed by network pharmacology and molecular docking analyses: Implications for differential clinical responses. (PubMed, Neurotherapeutics) - "Xanomeline plus trospium (KarXT) is a combination drug targeting muscarinic receptors with demonstrated efficacy against positive, negative, and cognitive symptoms of schizophrenia, although therapeutic effects on positive and negative symptoms do not differ significantly from risperidone and olanzapine. Distinct KarXT targets such as AKT1, IGF1, KDR, and CDC42, and clozapine targets including TNF, IL6, IFNG, and CXCL8 may explain differences in therapeutic efficacy. These bioinformatics findings support recent meta-analyses and provide guidance for more appropriate drug selection."

Journal • CNS Disorders • Inflammation • Psychiatry • Schizophrenia • CASP3 • CDC42 • CXCL8 • IFNG • IGF1 • IL17A • IL6 • KDR

Comparative efficacy and safety of clozapine vs. risperidone in schizophrenia and related disorders: An updated systematic review. (PubMed, Psychiatry Res) - "These findings underscore the need for future studies to prioritize efficacy measures, patient-centered outcomes, and cardiometabolic safety, to better guide clinical decision-making. Moreover, the integration of long-term observational studies into evidence appraisal is essential, as it offers a more pragmatic understanding of antipsychotic use in real-world settings."

Clinical • Journal • Review • CNS Disorders • Epilepsy • Psychiatry • Schizophrenia

Blood-based biomarkers of neuroaxonal and astroglial injury identify ultra-treatment-resistant schizophrenia. (PubMed, Eur Neuropsychopharmacol) - "UTRS is associated with a distinct peripheral biomarker profile reflecting astroglial and neuroaxonal injury. Plasma levels of GFAP and NfL, measured via ultrasensitive assays, may serve as promising biomarkers for identifying ultra-resistant schizophrenia and guiding precision psychiatry strategies."

Biomarker • Journal • CNS Disorders • Psychiatry • Schizophrenia • Targeted Protein Degradation • GFAP • NEFL • UBC

Metabolic Clearance of Physicochemically Diverse Pharmaceuticals in Cultured Fish Hepatocytes. (PubMed, Environ Toxicol Chem) - "Here we apply the well-established rainbow trout (Oncorhynchus mykiss) primary hepatocyte monolayer model to assess the hepatic clearance of five diverse APIs, namely propranolol, quetiapine, mycophenolic acid, clozapine and olaparib. Transcript profiling and enzyme activity assay results, on the other hand, showed both differences and similarities to currently available human data, emphasising the fact that the clearance and effects of APIs on metabolic and transport systems cannot be assumed to be directly comparable between fish and humans. Our data further support the good utility and replicability of the rainbow trout hepatocyte monolayer model and, in turn, its use in hazard identification and building risk profiles for APIs with wide-ranging properties."

Journal • ABCB1

Top 10 drugs most frequently associated with adverse events of myocarditis and pericarditis. (PubMed, Sci Rep) - "The following five drugs were consistently observed with both myocarditis and pericarditis: clozapine, mesalazine, smallpox vaccine, influenza vaccine, and COVID-19 mRNA vaccine. The other leading drugs differed by condition, with nivolumab, pembrolizumab, ipilimumab, valproate, and metronidazole appearing more frequently for myocarditis, and ribavirin, sulfasalazine, methotrexate, omalizumab, and heparin for pericarditis...Although our findings did not allow for causal inference, these findings highlight the importance of monitoring for possible adverse carditis cases when prescribing these drugs. Further studies are encouraged to investigate underlying mechanisms, assess individual patient risk factors, and explore the long-term impacts associated with myocarditis and pericarditis in relation to drug."

Adverse events • Journal • Cardiovascular • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Membrane Partition and Structural Reorganization Induced by Antipsychotics with Distinct Clinical Profiles. (PubMed, ACS Chem Neurosci) - "This study investigated two major APs with different pharmacological and clinical profiles: chlorpromazine, which exerts its clinical activity mainly through a strong antagonistic action at the D2R, and clozapine, the weakest D2R antagonist of all APs. The study aims to determine how the partitioning of the two APs modifies membrane order, phase transition, thickness, elasticity, phase separation, membrane integrity, and charge. Differences have been demonstrated between these two compounds, which may further differ both over time as they accumulate, as well as depending on their pre- or postsynaptic location."

Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

Investigating the effect of exercise on clinical symptoms, cognitive performance, and quality of life in schizophrenia patients treated with clozapine. (PubMed, Int J Psychiatry Clin Pract) - "According to the intergroup change analysis, the changes in the cognitive performance and psychological health sub-parameter of quality-of-life scores were significantly higher in the PEG than in the CG (p ≤ 0.05). The demonstrated improvement in cognitive performance and psychological health in patients with schizophrenia treated with Clozapine through physical exercise strongly advocates for the inclusion of structured exercise programs in comprehensive treatment plans."

HEOR • Journal • CNS Disorders • Psychiatry • Schizophrenia

Poisoning suicide due to paroxetine overdose toxicity aided by benzodiazepine and antipsychotic drugs. (PubMed, Int J Legal Med) - "It was classified as X61 in International Classification of Diseases (10th revision). This is the first fatal case reporting the simultaneous presence of antipsychotics (quetiapine and clozapine) and benzodiazepines (alprazolam) with toxic paroxetine levels."

Journal • CNS Disorders • Psychiatry

Case Report: Third-degree atrioventricular block and respiratory failure caused by clozapine poisoning. (PubMed, Front Pharmacol) - "Clozapine poisoning mostly causes symptoms such as accelerated heart rate, but in our patient's case, third-degree atrioventricular block and rhabdomyolysis symptoms occurred unusually. For clozapine poisoning, timely and appropriate management is crucial for the recovery of patients."

Journal • CNS Disorders • Depression • Psychiatry • Respiratory Diseases

Low-dose methotrexate as a potential treatment for schizophrenia via astrocytic and neuroimmune modulation. (PubMed, Schizophr Res) - "Our findings provide mechanistic insights into the potential antipsychotic-like effects of low-dose MTX in SCZ, involving astrocytic modulation and immune regulation. Further experimental medicine studies in clinical populations stratified by astrocytic and neuroinflammatory biomarkers are warranted to validate these findings."

Journal • CNS Disorders • Immunology • Psychiatry • Schizophrenia • CD73 • FAP • GFAP • IL6 • NT5E • STAT3

Randomised controlled trial of clozapine in resistant schizophrenia and schizoaffective disorder. (PubMed, J Psychopharmacol) - P2 | "CLZ was effective in reducing psychotic and affective symptoms in patients with dual psychosis, with better outcomes in SZD compared with TRS.EudraCT protocol trial:2021-001278-44 (Comparative analysis of the effectiveness of clozapine in resistant schizophrenia and schizoaffective disorder; clinicaltrialsregister.eu/ctr-search/trial/2021-001278-44/ES)."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Schizophrenia

Analysis of functional connectivity differences in Schizophrenia groups characterized by M1 receptor polymorphism during the N-Back task with fNIRS. (PubMed, Psychiatry Res Neuroimaging) - "The results revealed that wild-type individuals exhibit higher brain activation in task related cortical regions in the prefrontal and premotor cortex, but lower functional connectivity in the fronto-temporal network compared to non-wild-types. These differences indicate the possible role of genetic variations in shaping the neural response to clozapine, with wild-type individuals displaying more efficient neural strategies, whereas non-wild-type individuals rely on broader, less efficient compensatory processes to sustain cognitive performance."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Clozapine use and risk of infections in patients with schizophrenia in Hong Kong: a population-based cohort study. (PubMed, Lancet Psychiatry) - "Clinicians should balance the therapeutic benefits of clozapine with infection control measures, including regular monitoring and preventive strategies."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Psychiatry • Respiratory Diseases • Schizophrenia

Infection, inflammation, and personalisation: time for an integrated approach to clozapine monitoring. (PubMed, Lancet Psychiatry) - No abstract available

Journal • Infectious Disease • Inflammation

Pharmacoepigenetics in schizophrenia: Predicting drug response. (PubMed, World J Psychiatry) - "Antipsychotics such as clozapine (atypical) and haloperidol (typical) directly induce epigenetic changes by altering DNA methyltransferases and histone acetyltransferases, while indirectly affecting neuroinflammatory and stress response pathways. However, ethical and technical barriers to implementing strategies based on epigenetic regulation in clinical practice are fundamental challenges that need to be carefully addressed in this field. This review examined the epigenetic mechanisms involved in the efficacy of antipsychotic drugs."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Influence of pharmacokinetics-related gene polymorphisms on plasma levels of clozapine and its metabolites in Japanese patients with schizophrenia. (PubMed, PCN Rep) - "The SLCO1B1 T521C polymorphism may strongly impact the pharmacokinetics of N-desmethylclozapine, a major metabolite of clozapine. Therefore, the SLCO1B1 polymorphisms and plasma levels of N-desmethylclozapine as well as clozapine in patients with schizophrenia should be assayed for optimizing clozapine therapy."

Journal • PK/PD data • Agranulocytosis • CNS Disorders • Granulocytopenia • Psychiatry • Schizophrenia • ABCG2 • CYP1A2 • CYP2C19 • CYP3A5

A Case Report of Clozapine-Induced Cardiomyopathy. (PubMed, Cureus) - "This report presents the case of a 42-year-old male patient admitted with recurrent falls and urinary sepsis while on clozapine. He exhibited persistent tachycardia and drowsiness and was diagnosed with cardiomyopathy, likely induced by clozapine."

Journal • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Infectious Disease • Inflammation • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • Septic Shock

Occupational therapist-guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report. (PubMed, PCN Rep) - "Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment."

Journal • CNS Disorders • Hematological Disorders • Leukopenia • Neutropenia • Psychiatry • Schizophrenia

Higher risk of gastrointestinal stenosis and obstruction in clozapine-treated individuals with schizophrenia: a pharmacovigilance study based on the FDA adverse event reporting system database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Clozapine significantly elevates GSO risk, with delayed onset and polypharmacy exacerbating toxicity. Findings underscore the need for enhanced gastrointestinal monitoring in long-term clozapine users and reevaluation of co-prescribing practices to mitigate this underprioritized ADR."

Adverse events • Journal • CNS Disorders • Psychiatry • Schizophrenia

Repurposed Antipsychotics as Potential Anticancer Agents: Clozapine Efficacy and Dopaminergic Pathways in Neuroblastoma and Glioblastoma. (PubMed, Life (Basel)) - "This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Neuroblastoma • Oncology • Solid Tumor

Clozapine and Regulatory Inertia: Revisiting Evidence, Risks, and Reform. (PubMed, Healthcare (Basel)) - "The dismantling of the REMS program in early 2025 represents a pivotal moment, yet further reforms are urgently needed to align regulatory guidance with contemporary science. Ultimately, this article is a call to rediscover the clinical value of clozapine and to translate decades of knowledge into regulatory and clinical action."

Journal • CNS Disorders • Psychiatry • Schizophrenia