clozapine / Generic mfg. - LARVOL DELTA

Beyond Clozapine: Addressing Broader Metabolic Burden in Treatment-Resistant Schizophrenia. (PubMed, J Clin Psychopharmacol) - No abstract available

Journal • CNS Disorders • Psychiatry • Schizophrenia

Global trends in clozapine utilisation between 2014 and 2024: a longitudinal epidemiological study with data from 75 countries. (PubMed, Lancet Reg Health Eur) - "The absence of an association between haematological monitoring stringency and rate of clozapine utilisation suggests the need for measures beyond monitoring relaxation within policy and practice to systematically increase use. Provided by St Patrick's Mental Health Services."

Journal • CNS Disorders • Hematological Disorders • Psychiatry • Schizophrenia

Quantifying improvement of psychotic symptoms in clozapine-treated schizophrenia: clinical note analysis with large language models. (PubMed, Sci Rep) - "These findings demonstrate that LLMs can extract clinically meaningful symptom information from unstructured clinical text and capture treatment-related changes in psychosis. This approach premises a low-burden method for supporting clinical judgment using routinely collected EHR data."

Journal • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

Targeting cholinergic cells in a mouse model of Alzheimer's disease: Validating a quadruple transgenic model. (PubMed, Exp Neurol) - "To test the functionality of the Cre enzyme, a stimulating DREADD virus (AAV8-hSyn-DIO-hM3Dq-mCherry) was injected unilaterally into the nucleus basalis magnocellularis, and clozapine-N-oxide-induced c-Fos activation was compared between the two hemispheres...Additionally, the animals presented the pathophysiological hallmarks of AD in specific brain areas and maintained the typical behavioral alterations previously reported in 3xTg-AD mice. Thus, this strain seems to be appropriate for further studies."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Mood Disorders • Psychiatry • FOS

Updating clozapine prescribing guidelines in Italy: a step forward modernity. (PubMed, Eur Neuropsychopharmacol) - No abstract available

Journal

Involuntary Clozapine Treatment: A Systematic Review. (PubMed, Acta Psychiatr Scand) - "Although the body of evidence supporting the use of involuntary clozapine treatment is mostly drawn from small observational studies, their findings suggest that this last-resort option may save the life and promote recovery of people for whom other treatments have failed. Access to IM clozapine is currently restricted in most countries. Whether this barrier to clozapine treatment for severely ill people with impaired decision-making capacities should be overcome in other countries needs to be further addressed."

Journal • Review • CNS Disorders • Pain • Psychiatry

Electroconvulsive Therapy in Solid Organ Transplant Recipients: A Case Illustration and Systematic Review of 18 Cases. (PubMed, J ECT) - "His psychotic symptoms-including hallucinations and delusions-were refractory to multiple antipsychotics, including clozapine, but responded substantially to bifrontal electroconvulsive therapy (ECT), with preservation of cardiac graft function...These findings suggest that ECT is an effective consideration for refractory psychiatric syndromes in transplant recipients, even when immunosuppressant regimens cannot be altered. Careful pre-ECT evaluation, interdisciplinary collaboration, and vigilant peri-procedural monitoring remain essential for optimizing outcomes in this medically fragile population."

Journal • CNS Disorders • Depression • Psychiatry • Schizophrenia • Solid Organ Transplantation • Transplant Rejection • Transplantation

Drug-induced intestinal obstruction: insights from the FDA Adverse Event Reporting System. (PubMed, Ther Adv Drug Saf) - "Humira (10,356 cases) was the most frequently reported drug, followed by Remicade (2223 cases), Avastin (1580 cases), Vedolizumab (1385 cases), Clozaril (1229 cases), and Accutane (1088 cases). Disproportionality analysis revealed that the top five drugs with the highest ROR and PRR were Accutane, Teduglutide, Lonsurf, Avastin, and Lynparza...The high volume of reports associated with certain drugs may reflect usage patterns, underlying disease conditions, or reporting behaviors. Caution should be exercised in clinical translation."

Adverse events • Journal • Gastrointestinal Disorder

Dissecting Microglial Activation and Inhibition Windows to Optimize Stroke Recovery (ISC 2026) - "Clozapine-N-oxide (CNO) enables phase-specific activation or inhibition... Το date, we have validated the viral constructs were successfully delivered to the caudoputamen of Cx3cr1-Cre mice, confirming feasibility of targeted chemogenetic manipulation, and animals have subsequently undergone tMCAO. Longitudinal testing with the open field assay showed significant gait length reductions from baseline to post-stroke, demonstrating sensitivity to functional impairments. Immunohistochemistry revealed a dynamic MG response, with phagocytic microglia increasing through day 14 and declining thereafter."

Cardiovascular • Immunology • Infectious Disease • Inflammation • Ischemic stroke • CX3CR1

Effects of Dual Orexin Receptor Antagonists on Seizure Quality in Modified Electroconvulsive Therapy: A Pilot Study. (PubMed, J ECT) - "DORA use during m-ECT did not impair seizure quality, supporting their safe concomitant use. Findings were consistent across subgroup, agent, and dose-response analyses. Larger prospective trials are warranted to confirm these results."

Journal • CNS Disorders • Epilepsy • Insomnia • Sleep Disorder

Improving Adherence and Outcomes in Early Onset Schizophrenia: A Case Series on Role of Clozapine and Long-Acting Injectables for Refractory Courses. (PubMed, Cureus) - "Across cases, clozapine alone or in combination with an LAI was associated with substantial improvement in positive symptoms, behavioral regulation, and overall clinical stability, allowing transition to the least restrictive settings.  These findings illustrate the potential usefulness of clozapine and clozapine combined with LAI medications in adolescents with treatment-resistant EOS. They highlight the importance of early consideration of clozapine within a comprehensive treatment framework and point out the need for rigorous prospective research to guide clinical practice."

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

Variables associated with clinical outcomes and switching from unilateral to bitemporal electroconvulsive therapy: a retrospective study. (PubMed, Front Psychiatry) - "Within the switched subgroup, clozapine use and ECT charge increased during BT sessions compared to the RUL course (p < 0.05). Initiating treatment with RUL ECT and transitioning to BT ECT when necessary offers a pragmatic balance between tolerability and efficacy. Certain clinical variables may guide clinicians in anticipating the need for switching from a RUL to a BT setup."

Clinical data • Journal • Retrospective data • CNS Disorders • Epilepsy • Mental Retardation • Psychiatry

RAKGEOCBT: The Combination of Pharmacotherapy and Cognitive Behavioral Psychotherapy Under the Recovery Perspective. (clinicaltrials.gov) - P1 | N=107 | Active, not recruiting | Sponsor: Rakitzi, Stavroula | Recruiting ➔ Active, not recruiting | N=40 ➔ 107

Enrollment change • Enrollment closed • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Obsessive-Compulsive Disorder • Personality Disorder • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

Risk of neutropenia-related hospitalisation among clozapine initiators. (PubMed, BMJ Ment Health) - "Despite removal of the REMS programme, it is important for prescribers to monitor patients for neutropenia after initiating clozapine."

Journal • Agranulocytosis • CNS Disorders • Granulocytopenia • Hematological Disorders • Neutropenia • Psychiatry • Schizophrenia

CLOZAPINE Response in Biotype-1 (clinicaltrials.gov) - P4 | N=524 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial primary completion date: Dec 2025 ➔ Apr 2026

Trial primary completion date • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

DREADD agonist Clozapine-N-oxide, but not Compound 21, impairs spatial memory encoding. (PubMed, bioRxiv) - "Nonetheless, we find that CNO administration impairs OLM encoding, while C21 does not. Together, these findings highlight a previously unrecognized behavioral effect of CNO administration on hippocampus-dependent memory formation-even in the absence of DREADD expression-and indicate that C21 may be a preferable ligand for chemogenetic studies examining memory and hippocampal function."

Journal • Mood Disorders • Psychiatry

The association of clozapine treatment periods with incidence of exposure to assault and head injuries - a cohort study of electronic health records. (PubMed, Front Psychiatry) - "This effect remained statistically significant after covariate adjustment (0.46 (0.29-0.74); 0.40 (0.22-0.71) in men; 0.64 (0.29-1.43) in women. Clozapine treatment was thus associated with a substantially reduced risk of exposure to assault and head injuries."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Decoding the immunopharmacological basis of ECT-induced clozapine level elevation: Insights from a Quantitative Systems Pharmacology model. (PubMed, Eur J Pharmacol) - "The QSP model provides a robust, mechanistically plausible explanation for the observed ECT-clozapine interaction, identifying the inflammatory cascade as the critical driver of impaired clozapine metabolism. The model serves as a powerful tool for simulating patient risk and provides a quantitative foundation for developing personalized, model-informed dosing strategies to enhance the safety of this crucial concomitant therapy."

Journal • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Psychiatry • Schizophrenia • CRP • CYP1A2 • DRD2 • IL6

Association Between Levels of the Acute Phase Proteins Alpha-1-Acid Glycoprotein and C-Reactive Protein and Serum Concentrations of Clozapine: A Study of 1106 Therapeutic Drug Monitoring Samples. (PubMed, Basic Clin Pharmacol Toxicol) - "Our findings support and extend previous case reports and studies, suggesting that increased AGP levels during inflammatory states may play a significant role in the rise of clozapine plasma concentrations observed during illness. We propose that in addition to the clozapine concentration, CRP levels and clinical signs of adverse effects and toxicity should be closely monitored in patients with infectious or inflammatory diseases."

Journal • Infectious Disease • Inflammation • CRP • PROS1

Disentangling violence in schizophrenia: Interactions between symptom trajectories, conduct disorder, and pharmacotherapy. (PubMed, Schizophr Res) - "These findings highlight the importance of interactions among symptoms, conduct disorder, and medication in determining violence. They also point to the multifactorial etiology of violence in patients with schizophrenia and to the need for tailored treatment strategies to effectively reduce violence, especially in high-risk population."

Journal • Behavior Disorders • CNS Disorders • Depression • Psychiatry • Schizophrenia

Aberrant motor cortical plasticity in antipsychotic-resistant schizophrenia: A cross-sectional study using transcranial direct current and magnetic stimulation. (PubMed, Schizophr Res) - "The results reaffirm the finding of impaired motor cortical plasticity in ARS. Additionally, we note that URS with a higher symptom burden, treatment resistance and poorer functioning had the poorest motor cortical plasticity. Future studies could explore the potential of cortical plasticity as a predictive, mechanistic, and theranostic biomarker."

Journal • Observational data • CNS Disorders • Psychiatry • Schizophrenia

Pharmacological rescue of social deficits in rats featuring Disrupted-in-Schizophrenia-1 (DISC1) protein aggregation. (PubMed, Schizophrenia (Heidelb)) - "Here, we tested whether continuous administration of atypical antipsychotics amisulpride or clozapine would rescue social deficits in tgDISC1 rats. Together, these findings demonstrate that amisulpride, a selective D2/D3 receptor antagonist, rescues social adaptability deficits linked to aberrant DISC1 signaling. The results also highlight the success of our precision psychiatry approach: the biological definition of a subset of schizophrenia by identifying DISC1 protein aggregates, the generation of a corresponding animal model and a successful pharmacotherapy of a clinically relevant phenotype."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Sympathetic Neurons Modulate Immune Responses to Inner Ear Bacterial Infections (ARO 2026) - "The importance of sympathetic-immune interactions was tested by ablating sympathetic axons via administration of 6-hydroxydopamine (6-OHDA) and by activating sympathetic neurons using the LSL-Gq-DREADD mouse line with chronic administration of ligand clozapine-N-oxide (CNO), followed by induction of BM, behavioral assays, and histological evaluation... Our data suggest sympathetic neurons affect the extent of inflammatory activity in the inner ear during BM infection. Current work aims to dissect molecular and cellular mechanisms of neuroimmune interactions in the inner ear, with potential implications for preserving hearing and vestibular function during infections."

Cholera • CNS Disorders • Infectious Disease • Otorhinolaryngology • Pneumonia • Vertigo

Development of a New Tinnitus Model Using Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-Based Chemogenetic Technology (ARO 2026) - "On every other day of testing, animals received intraperitoneal (i.p.) injections of clozapine-N-oxide dihydrochloride (CNO), a chemogenetic actuator, at a dose of 5 mg/kg, one hour before testing... SBAD scores suggest that selective modulation of IC excitatory neurons via chemically activated DREADDs can lead to tinnitus-associated behavior. Video tracking analyses identified 9 behavioral metrics that may be associated with tinnitus percept. Future studies will continue to build these tinnitus-associated behavioral profiles."

Otorhinolaryngology

Reply to "Beyond Clozapine: Addressing Broader Metabolic Burden in Treatment-Resistant Schizophrenia". (PubMed, J Clin Psychopharmacol) - No abstract available

Journal • CNS Disorders • Psychiatry • Schizophrenia