Objective: The use of clozapine is restricted due to its serious side effects, particularly bone marrow suppression, which occurs at anaverage rate of 1%. These side effects are markedly related to blood concentrations of clozapine and its metabolite nor-clozapine.Therefore, therapeutic drug monitoring is recommended for clozapine. Currently, laboratory monitoring of bone marrow suppressionincludes neutrophil count follow-up. However, using early-changing biomarkers may be more effective in detecting and preventing this sideeffect before neutropenia develops. Therefore, we aimed to evaluate serum clozapine and nor-clozapine levels and their relationship withearly parameters reflecting bone marrow activity in complete blood count (CBC), immature granulocyte (IG) for neutrophils, mean plateletvolume (MPV) and platelet-to-large cell ratio (P-LCR) for platelets in patients with schizophrenia receiving clozapine.Methods: Fifty-one patients with schizophrenia receiving clozapine were included in the study. Of these, 49% (n=25) were on a low dose(600 mg/day) clozapine. CBCparameters—especially IG, MPV and P-LCR—and serum clozapine/nor-clozapine levels along with clozapine doses were recorded on thesame day. The relationship between serum drug concentrations and CBC parameters was evaluated separately for the total patients anddose groups.Results: There was no correlation between clozapine dose and serum clozapine or nor-clozapine concentrations. None of the patientshad neutropenia or agranulocytosis. Serum clozapine and nor-clozapine levels negatively correlated with P-LCR (r=-0.402, p=0.006 andr=-0.465, p=0.001, respectively) and MPV (r=-0.294, p=0.036 and r=-0.397, p=0.004, respectively); positively correlated with neutrophil(r=0.381, p=0.011 and r=0.387, p=0.009, respectively) and IG counts (r=0.346, p=0.018 and r=0.335, p=0.023, respectively); but notwith other CBC sub-parameters. Although the clozapine dosing differed between the two groups, the serum levels of clozapine and norclozapine were not significantly different (p=0.078 and p=0.058, respectively). Furthermore, in the middle dose group, serum clozapineand nor-clozapine levels were negatively correlated with P-LCR (rho=-0.547, p=0.007 and rho=-0.636, p=0.001, respectively), consistentwith the total group.Conclusion: Monitoring early biomarkers reflecting bone marrow activity, such as P-LCR for platelets and IG for neutrophils, alongside serumclozapine and nor-clozapine levels, is promising for predicting and preventing bone marrow suppression in patients receiving clozapine,thereby protecting against this serious side effect. However, our findings need to be supported by further research.
Kılıç et al. (Fri,) studied this question.