Clozapine Efficacy, Type of Titration and Therapeutic Drug Monitoring Using Chemical Methods for Serum Level Assessment

Abstract

Approximately 30% of patients are included in treatment-resistant schizophrenia and clozapine remains the only antipsychotic with proved superior efficacy in these cases. Currently, although clozapine is considered as the most effective pharmacological intervention for treatment-resistant schizophrenia in all national guidelines, its use is suboptimal due to doctors� concerns about tolerability and inappropriate adherence of patients to haematological monitoring required for early detection of severe neutropenia. Although treatment guidelines recommend the use of clozapine starting with a dose of 12.5-25 mg/day and gradual increase over a 2-week period until the therapeutic dose is reached, this recommendation was not derived from rigorous controlled studies. Slow or standard titration of clozapine increases the need for additional psychotropics and risks associated with antipsychotic polypharmacy, and can unnecessarily prolong the patient�s suffering and the length of hospitalization. A relationship between a faster titration and a higher incidence of clozapine-induced dangerous adverse effects has not been clearly demonstrated by clinical trials. Therapeutic drug monitoring is of great importance for drugs with a high inter-individual variability in serum concentration, a narrow therapeutic range or serious toxic side effects.