# Predicting clozapine toxicity risk during ECT augmentation using an inflammation-based quantitative systems pharmacology framework - URL: https://alisanburak.com/en/wcp-2026-posterler/so103 - Language: en - Last updated: not specified - Page title: Predicting clozapine toxicity risk during ECT augmentation using an inflammation-based quantitative systems pharmacology framework | WCP 2026 Summary > Electroconvulsive therapy–induced cytokine surges progressively suppress CYP1A2 activity, leading to clozapine accumulation and toxicity-associated D2 receptor… This page was translated automatically from Turkish. [Read the original](https://alisanburak.com/wcp-2026-posterler/so103) This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it. SO103 Brief Oral Poster PresentationPsychopharmacologyQuantitative systems pharmacology modeling study # Predicting clozapine toxicity risk during ECT augmentation using an inflammation-based quantitative systems pharmacology framework PREDICTING CLOZAPINE TOXICITY RISK DURING ECT AUGMENTATION USING AN INFLAMMATION-BASED QSP FRAMEWORK Presenter: Archana Mishra Country: India Institution: All India Institute of Medical Sciences New Delhi, Department of Pharmacology Session: 2790 - PARALLEL SHORT ORAL POSTER SESSIONS: PSYCHOSIS & SCHIZOPHRENIA - Part II Date: Thu, 24.09.2026 Electroconvulsive therapy–induced cytokine surges progressively suppress CYP1A2 activity, leading to clozapine accumulation and toxicity-associated D2 receptor occupancy after the fourth session. The study aimed to develop and validate a quantitative systems pharmacology (QSP) model to test whether electroconvulsive therapy (ECT) increases clozapine levels by triggering inflammation. The modular model, built in Python 3.8, integrated a two-compartment physiologically based pharmacokinetic structure, the ECT-induced inflammatory response, and CYP1A2 enzyme inhibition mediated by IL-6, CRP, and TNF-alpha. Parameters were derived from published clinical and population pharmacokinetic data, in vitro cytokine–CYP1A2 data, and therapeutic drug monitoring records, including cases with more than threefold increases in concentration; successful validation was defined as a prediction error within 25% of observed concentrations. A standard six-session ECT course delivered over two weeks (Monday, Wednesday, Friday) was simulated in patients at clozapine steady state, with twice-daily dosing over 336 hours and 3,000 time points. ECT produced rapid, transient increases of more than 100-fold in IL-6, a delayed but sustained approximately 15-fold elevation in CRP, and lower-amplitude peak-and-decline patterns of approximately 10-fold in TNF-alpha; CYP1A2 activity decreased progressively to approximately 30% of baseline. Dopamine D2 receptor occupancy rose from approximately 51% before ECT to more than 83% after six sessions, exceeding the toxicity-associated threshold of 80% after the fourth session. The model predicted 3.7-fold clozapine accumulation, while retrospective assessment of fit yielded results consistent with the observed two- to sixfold increases in concentration. Sensitivity analysis identified the magnitude of the IL-6 surge and the potency of CYP1A2 inhibition as the primary determinants of toxicity risk, together accounting for approximately 70% of the variance. The model is proposed as a model-based risk prediction tool to reduce the risks of delirium, seizures, myocarditis, and neutropenia during ECT augmentation through a 25% to 50% dose reduction before ECT, monitoring stratified by metabolizer status, and individualized ECT scheduling. [View the original poster](https://cslide.ctimeetingtech.com/wcp26/attendee/eposter/file/358) How to cite this study APA 7: Mishra, A., et al. (2026, September 24). Predicting clozapine toxicity risk during ect augmentation using an inflammation-based qsp framework [Poster presentation]. 26th WPA World Congress of Psychiatry (WCP 2026), Stockholm, Sweden. https://cslide.ctimeetingtech.com/wcp26/attendee/eposter/file/358 Vancouver: Mishra A, et al. Predicting clozapine toxicity risk during ect augmentation using an inflammation-based qsp framework [poster]. 26th WPA World Congress of Psychiatry (WCP 2026); 2026 Sep 23-26; Stockholm, Sweden. Available from: https://cslide.ctimeetingtech.com/wcp26/attendee/eposter/file/358 Author names and title formatting were generated automatically from the congress system; please check them against the original poster before use. ## On the same topic - [Açığı kapatmak: erişkin DEHB ilacı başlanmadan önce EKG sevk uyumunun iyileştirilmesi, kapalı döngü klinik denetim](https://alisanburak.com/en/wcp-2026-posterler/ev0088) - [Anksiyete bozukluğu olan hastalarda psikobiyotik müdahalesi: ısıl işlem görmüş Lactobacillus paracasei PS23'ün etkilerini inceleyen çift kör randomize kontrollü çalışma](https://alisanburak.com/en/wcp-2026-posterler/ev0126) - [Otizm spektrum bozukluğunda bumetanidin tedavi edici potansiyeli: güncel kanıtlar ve gelecek yönelimleri](https://alisanburak.com/en/wcp-2026-posterler/ev0157) - [Verbaskozid ile otizm spektrum bozukluğu tedavisinin mekanizmaları: ağ farmakolojisi, moleküler yerleştirme ve moleküler dinamik temelli inceleme](https://alisanburak.com/en/wcp-2026-posterler/ev0172) - [Otizm spektrum bozukluğunun çekirdek belirtilerinin tedavisinde kannabidiol: sistematik derleme](https://alisanburak.com/en/wcp-2026-posterler/ev0186) [All WCP 2026 summaries](https://alisanburak.com/en/wcp-2026-posterler) --- Kaynak / Source: https://alisanburak.com/en/wcp-2026-posterler/so103 İletişim / Contact: Bağdat Caddesi, Veli Güneysu Apt. No:453 K:4 D:9, Suadiye / Kadıköy, İstanbul · +90 532 642 95 25 · info@alisanburak.com · https://alisanburak.com/bagdat-caddesi-psikoterapi-iletisim