Plasma clozapine levels correlate with EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation, but not QTc or myocarditis.
Systematic Review
Do plasma clozapine levels correlate with the occurrence of adverse drug reactions in patients with treatment-resistant schizophrenia?
Certain adverse effects of clozapine, such as metabolic syndrome and constipation, correlate with plasma levels, while others like myocarditis and neutropenia do not, highlighting the nuanced role of therapeutic drug monitoring.
Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
Σκώκου et al. (Fri,) conducted a systematic review in Treatment-resistant schizophrenia. Plasma clozapine levels was evaluated on Correlation of adverse effects to plasma clozapine levels. Plasma clozapine levels correlate with EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation, but not QTc or myocarditis.