clozapine / Generic mfg. - LARVOL DELTA

Effects of Antiepileptic Drugs, Carbamazepine and Phenytoin, on Plasma Concentrations of Clozapine and Its N-Desmethyl and N-Oxide Metabolites in Japanese Patients With Schizophrenia. (PubMed, Neuropsychopharmacol Rep) - "However, for phenytoin, which is also known as a CYP3A4-inducer, the drug interactions with CLZ were not very clear due to the small limited data. These pharmacokinetic findings in only two cases must be confirmed by further investigations."

Journal • CNS Disorders • Psychiatry • Schizophrenia • CYP1A2 • CYP3A4

Following the Action of Atypical Antipsychotic Clozapine and Possible Prediction of Treatment Response in Schizophrenia. (PubMed, Life (Basel)) - "Clozapine is one of the most effective antipsychotics, and there is potential to improve performance by combining it with different compounds to limit adverse effects or by augmenting it with other antipsychotics (amisulpride, paliperidone), other active substances with different properties (minocycline, N-acetylcysteine, memantine), or alternative therapies (electroconvulsive therapy, repetitive transcranial magnetic stimulation). There are also significant steps in optimizing clozapine efficacy by predicting treatment response, which could be determined by testing the following: plasma levels of clozapine N-oxide and N-desmethylclozapine, serum levels of neurotrophins and glutamate, genetic testing, the polygenic risk score, morphometry, or even the identification and accurate determination of persistent negative symptoms."

Journal • Review • CNS Disorders • Depression • Psychiatry • Schizophrenia • ADRA1B • RPS6

Critical components of 'Early Intervention in Psychosis': national retrospective cohort study. (PubMed, Br J Psychiatry) - "Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery."

Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Why is Clozapine uniquely Effective in Treatment Resistant Schizophrenia? (PubMed, Biol Psychiatry) - "Clozapine's multi-receptor profile enables it to have beneficial actions on the non-psychotic symptoms common in TRS: its ability to bind to histamine H1, serotonin 5-HT1A and GABA-B receptors offers an explanation for its anxiolytic actions while effects on 5-HT1A, 5-HT2A and 5-HT7 receptors likely underly its antidepressant properties. Clozapine shares these properties with olanzapine and quetiapine but its affinity for muscarinic receptors may be the mechanism by which it is more effective in TRS."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Clinical and inflammatory markers associated with metabolic dysfunction-associated fatty liver disease in a cohort of individuals with chronic schizophrenia (FACE-SZ). (PubMed, J Psychosom Res) - "Although not generalizable to all patients with schizophrenia, this study confirms the high prevalence of MAFLD in individuals with schizophrenia. Psychiatrists should promote healthy lifestyle changes, such as weight control, improved diet, better sleep, and increased physical activity, to improve both physical health and quality of life in these patients."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Psychiatry • Schizophrenia • IL12A • TNFA

Comparative Toxicokinetics and Biomarker Responses of Typical Psychiatric Pharmaceuticals in Daphnia magna. (PubMed, Toxics) - "In this study, eight typical PDs [carbamazepine (CBZ), citalopram (CIT), sertraline (SER), venlafaxine (VLF), amitriptyline (AMT), chlorpromazine (CPM), quetiapine (QTP) and clozapine (CLZ)] were selected to study the uptake, depuration and biological effects of PDs in Daphnia magna. The Ku of PDs, oxidative stress and metabolic level of D. magna combine to affect BCF levels together. In conclusion, this study contributes to a better understanding of the toxicokinetics and biochemical responses of PDs in D. magna and potential mechanisms of action, which may allow for a better assessment of their environmental health risks to aquatic ecosystems."

Biomarker • Journal • Pain • Psychiatry

Asenapine-induced severe dystonia in a patient with schizophrenia: medication error due to sound-alike drug. (PubMed, BMJ Case Rep) - "The misinterpretation of the sound-alike drugs Azapin (clozapine) and asenapine caused an acute dystonic reaction. First, it uncovers a medication error due to a sound-alike drug and emphasises the importance of paying attention to national guidelines since first-line treatment can differ between countries. These factors combined increase the risk of medication error with potentially fatal consequences."

Journal • CNS Disorders • Dystonia • Movement Disorders • Psychiatry • Schizophrenia

Impact of the transcription factor nuclear factor 1 B T>C polymorphism on clozapine metabolism in vivo and expression of intestinal transporters in vitro. (PubMed, Drug Metab Dispos) - "In vitro experiments further indicate that NFIB may regulate the expression of intestinal efflux transporters. Both findings provide a future foundation for genotype-guided dosing of clozapine in patients suffering from treatment-resistant schizophrenia."

Journal • Preclinical • CNS Disorders • Psychiatry • Schizophrenia • ABCB1 • ABCC1 • ABCG2 • NFIB

Impact of lot-to-lot variation in absolute neutrophil count measured by a point-of-care device in patients receiving clozapine treatment. (PubMed, Clin Biochem) - "Our study combines patient-level data with method comparisons to highlight the impact of lot variation on results with potential consequences, including increased rates of repeated blood sampling. While point-of-care devices may facilitate lowering barriers for clozapine use, provider education and additional quality metrics are needed to inform testing."

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

Striatal cholinergic interneuron pause response requires Kv1 channels, is absent in dyskinetic mice, and is restored by dopamine D5 receptor inverse agonism. (PubMed, Elife) - "Remarkably, this pause is absent in parkinsonian mice rendered dyskinetic by chronic L-DOPA treatment but can be reinstated acutely by the inverse D5R agonist clozapine...This pause is mediated by delayed rectifier Kv1 channels, which are tonically blocked in dyskinetic mice by a mechanism depending on D5R ligand-independent activity. Targeting these alterations may have therapeutic value in Parkinson's disease."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • DRD2

Inhibition of the nucleus accumbens core with DREADDs after acute and repeated exposure to oxycodone reduces locomotor activity in female but not male Rattus norvegicus. (PubMed, Neurosci Lett) - "Following a 7-day drug-free period, all rats received oxycodone challenge (1 mg/kg, i.p.) with clozapine-N-oxide (CNO, 3 mg/kg) to activate DREADD-mediated inhibition...These findings reveal sex differences in NAc involvement in acute and chronic oxycodone induced locomotor activity. Our results underscore the need for sex-specific considerations in addiction research."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse

Ferroptosis as a potential molecular mechanism of bipolar disorder. (PubMed, Transl Psychiatry) - "Moreover, some BD treatments, such as lithium, haloperidol, olanzapine, clozapine, valproic acid, and electroconvulsive therapy, show anti-ferroptosis action in other contexts...In addition, we call for studies on different BD models to assess the expression of ferroptosis markers. Our hypothesis has substantial implications if validated, including the use of ferroptosis-related genes and ferroptosis markers as a prognostic marker for BD and a potential therapeutic target based on ferroptosis inhibitors."

Journal • Review • Addiction (Opioid and Alcohol) • Autism Spectrum Disorder • Bipolar Disorder • CNS Disorders • Depression • Genetic Disorders • Inflammation • Major Depressive Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

Relationship between regional prescriptions of lithium and clozapine and suicide mortality in children and adolescents in France between 2014 and 2019. (PubMed, J Affect Disord) - "Keeping in mind the limitations inherent to spatial study design, these preliminary findings are consistent with a possible antisuicide effect of clozapine in the pediatric population, while the effect of lithium is less clear. Even in the context of the French free-of-charge healthcare system, major spatial inequities exist in access to these medications for youths, partly underlaid by social disparities and medical demography."

Journal • Behavior Disorders • Bipolar Disorder • CNS Disorders • Mental Retardation • Pediatrics • Psychiatry • Schizophrenia

In vivo assessment of GABAergic inhibition and glutamate facilitation in treatment-resistant schizophrenia: a TMS study integrating clinical, cognitive, and neurophysiological evaluations. (PubMed, Schizophrenia (Heidelb)) - "Clozapine treatment is often delayed, underscoring the urgent need for an early potential signature of TRS...SICI deficits significantly correlated with negative (r = 0.524, padj = 0.03) and autistic (r = 0.517, padj = 0.03) symptom severity as assessed by the PANSS negative score and Positive and Negative Syndrome Scale Autism Severity Score (PAUSS). Our findings point to a neurophysiological continuum in schizophrenia, with TRS patients demonstrating the most pronounced cortical hyperexcitability and impaired plasticity, and non-TRS patients showing intermediate deficits."

Journal • Preclinical • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Psychiatry • Schizophrenia

Efficacy and tolerability of pharmacological interventions for schizophrenia non-responsive to prior treatment: a systematic review and network meta-analysis. (PubMed, EClinicalMedicine) - "Clozapine showed superior efficacy for overall symptoms compared to haloperidol, chlorpromazine, quetiapine, and sulpiride (SMDs 0.35 to 1.00). It slightly outperformed olanzapine for positive symptoms (SMD 0.19; 95% CI 0.00 to 0.37) and risperidone for response rates (OR 0.64; 95% CI 0.41 to 1.01). Clozapine combinations with amisulpride, duloxetine, memantine, mirtazapine, topiramate, and ziprasidone improved overall symptoms more than clozapine monotherapy (SMDs -1.53 to -0.51)...These results emphasise the need for personalised treatment, further research comparing non-clozapine antipsychotic combinations to high-dose clozapine monotherapy, and studies on long-term outcomes. None."

Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Exploring the pathophysiology underlying clozapine-induced enhancement of glutamatergic transmission through L-glutamate and D-serine release associated with pannexin1 hemichannels. (PubMed, Br J Pharmacol) - "Enhanced glutamatergic transmission by chronic administration of therapeutically relevant concentrations of clozapine involves increased L-BAIBA signalling, which activates Src signalling via III-mGluR agonistic action, without affecting pannexin1 expression. Activation of pannexin1-hemichannel activity induced by Src signalling and III-mGluR may play an important role in the effectiveness of clozapine in TRS."

Journal • CNS Disorders • Psychiatry • Schizophrenia

A psychiatric medication, clozapine, induces autophagy and apoptosis in breast cancer cells through reactive oxygen species. (PubMed, PLoS One) - "Additionally, inhibition of autophagy using chloroquine enhances clozapine-induced apoptosis and further reduces cell viability. The addition of α-Tocopherol similarly rescued these cells from clozapine-induced cell death. Overall, our study demonstrates that clozapine suppresses the growth of both MCF-7 and MDA-MB-231 breast cancer cells by inducing cytotoxicity via ROS and autophagy, highlighting its potential as a therapeutic agent, especially in combination with autophagy inhibitors."

Journal • Breast Cancer • CNS Disorders • Hormone Receptor Negative Breast Cancer • Oncology • Psychiatry • Solid Tumor • CCND1 • CDK4 • CDK6 • CDKN1A • ER

Gi-DREADD activation decreases Epithelial Na+ channel activity in renal principal cells. (PubMed, Physiol Rep) - "We demonstrated that pharmacogenetic activation of Gq (Gq-DREADD) exclusively in principal cells by Clozapine-N-oxide (CNO) reduced ENaC activity in renal tubules, promoting natriuresis that lowered elevated blood pressure in the DOCA-salt model of hypertension...Our results showed that Gi-DREADD, expressed exclusively in renal principal cells, activated by CNO reduced ENaC activity and significantly increased urinary Na+ excretion compared to CNO-treated littermates. These findings provide for the first time that target activation of Gi signaling exclusively in PCs is sufficient to decrease ENaC activity and increase dependent urinary Na+ excretion in live animals."

Journal • Cardiovascular • Hypertension

Clozapine Withdrawal Catatonia Successfully Treated with Olanzapine: A Case Report. (PubMed, J Acad Consult Liaison Psychiatry) - No abstract available

Journal

FDA Officially Eliminates Clozapine REMS (Psychiatric Times) - "On June 13, 2025, the US Food and Drug Administration (FDA) officially eliminated the clozapine REMS, and all REMS operations ceased...Although clozapine still carries a risk of severe neutropenia, the FDA has determined that the clozapine REMS is no longer necessary, and by eliminating the REMS, they expect to improve access to clozapine. Notably, the FDA still recommends monitoring patients’ ANC and information about severe neutropenia remains in the prescribing information for all clozapine medicines. From here on out, determination of the appropriateness of clozapine for a patient remains solely with the prescriber."

FDA event • Schizophrenia

Higher clozapine concentration-to-dose ratios at week 1 after initiation are associated with increased risk of clozapine-associated fever in Japanese patients with schizophrenia. (PubMed, Front Psychiatry) - "Patients with fever had significantly higher C/D ratios on day 8 than those without fever (2.33 vs. 1.47; P < 0.005). Measuring blood clozapine levels on day 8 may help to better estimate the risk of clozapine-associated fever in patients with schizophrenia."

Journal • Cardiovascular • CNS Disorders • Infectious Disease • Inflammation • Pneumonia • Psychiatry • Schizophrenia

Multilevel Neuroimaging Insights Into Electroconvulsive Therapy Mechanisms in Clozapine-Refractory Schizophrenia: A Comparative Perspective With Depression. (PubMed, Biol Psychiatry Glob Open Sci) - No abstract available

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

A Randomized Controlled Trial of an Extension for Community Healthcare Outcomes (ECHO) Tele-mentoring Program to Increase Clozapine Utilization. (PubMed, Schizophr Bull) - "A statewide tele-mentoring program increased prescriber knowledge and competence in clozapine prescribing among those attending most ECHO sessions. Median time to clozapine discontinuation was double in the ECHO group, however, neither this nor rates of prescribing were statistically significantly different from control. Additional support is needed to motivate clozapine prescribing beyond providing education and increasing confidence in clozapine management."

Journal • Hematological Disorders

Clozapine for older adults with severe mental illness: a systematic review and expert recommendations for clinical practice. (PubMed, Expert Rev Clin Pharmacol) - "The single controlled study in a small sample did not find clozapine superior to chlorpromazine. Further studies are required to document how to adapt clozapine treatment to physiological aging or incident comorbidities and co-prescriptions. www.crd.york.ac.uk/prospero identifier is CRD420251038600."

Journal • Review • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hypotension • Infectious Disease • Pneumonia • Respiratory Diseases

Polymorphisms of the HTR2C Gene as Predictors of Metabolic Disturbances During Clozapine Therapy: A Systematic Review and Meta-Analysis. (PubMed, J Clin Med) - " These results highlight the need for large-scale, prospective studies across diverse populations to validate associations and optimize personalized monitoring strategies. Implementing genetic screening could enhance early intervention, improving long-term outcomes for clozapine-treated patients."

Journal • Retrospective data • Review • CNS Disorders • Genetic Disorders • Metabolic Disorders • Psychiatry • Schizophrenia