NCMD Research Seminar Series 21st November 2025

Presenter: Dr Georgios Schoretsanitis, Senior Physician, Psychiatry University Hospital, Zurich, Chief Director, Professor Dr. Med. E. Seifritz.

'Therapeutic Drug Monitoring in dose titration of clozapine '

Clozapine remains the gold standard for treatment-resistant schizophrenia, offering superior efficacy compared to other antipsychotics. However, its use is complicated by the risk (as well as concerns) of serious adverse effects, including agranulocytosis, myocarditis, and seizures. Therapeutic Drug Monitoring (TDM) is an essential tool in optimizing clozapine therapy, ensuring both efficacy and safety during dose titration.

TDM involves measuring plasma clozapine and its active metabolite, norclozapine, to guide individualized dosing. The therapeutic reference range for clozapine is generally considered to be 350–600 ng/mL, though optimal levels may vary depending on clinical response and tolerability. During dose titration, TDM helps clinicians navigate the balance between achieving therapeutic concentrations and minimizing toxicity, particularly in patients with polypharmacy, physical comorbid conditions including inflammation, which can alter clozapine metabolism.

The process of dose titration with TDM allows for a more precise and patient-tailored approach. Initial dosing is typically conservative, with gradual increases based on clinical response and plasma levels. Regular monitoring can also detect non-adherence, which is common in schizophrenia, and
guide interventions to improve treatment outcomes.

The presentation will review the principles of TDM in clozapine therapy, discuss practical considerations for implementation, and highlight its role in improving patient outcomes in treatment-resistant schizophrenia.

Having worked across multiple therapeutic areas and international collaborations, including earning a PhD in genetic epidemiology and leading projects with the European Commission and WHO, he brings a unique perspective to transforming real-world data into meaningful evidence that supports clinical decision-making and product development across all stages of the healthcare continuum.