De Novo Seizures, Obsessive Compulsive Symptoms and Neutropenias in Patients on Clozapine: A Retrospective Cohort Study

Abstract

Background: Clozapine has well-documented inter-ethnic variations in pharmacokinetics. There is a paucity of data about clozapine use and associated adverse events such as seizures, obsessive compulsive symptoms, neutropenia, and agranulocytosis, from India. Methods: This retrospective cohort study followed up 228 patients initiated on clozapine in a tertiary care referral center in India for an average of 10 years. We calculated incidence rates of new-onset seizures, new-onset obsessive compulsive symptoms, agranulocytosis, and neutropenia. We collected data on doses of clozapine used and serum assays and calculated concentration-to-dose (C/D) ratios. We also collected relevant clinical details about clozapine-induced seizures. Results: In the sample, 16.8% had new-onset seizures, 12.3% had new-onset OC symptoms, 2.7% had neutropenia, and 0.9% had agranulocytosis. The mean C/D ratio was 2.09 (SD = 1.8). Almost half (46.3%) of available serum assays were in the supra-therapeutic range. Seizures were associated with a higher clozapine dose at one year (OR = 1.003; 95%CI = 1.000–1.006; P value = 0.045) and the presence of positive psychotic symptoms at one year (OR = 4.214; 95%CI = 1.894–9.373; P < 0.001). Conclusion: Compared to existing literature, Indians have a higher rate of clozapine- related seizures and need lower doses to reach therapeutic serum levels.