Relationship between Clozapine-Induced Electroencephalogram Abnormalities and Serum Concentration of Clozapine in Japanese Patients with Treatment-Resistant Schizophrenia

Abstract

Objective: The objective of this study was to investigate the relationship between the serum concentration of clozapine (C-CLZ), Ndesmethylclozapine (N-CLZ) and the daily dose of CLZ (D-CLZ), and the relationships among CLZ and electroencephalogram (EEG) abnormalities.

Methods: Twenty-eight patients were recruited to this study, but 8 patients were excluded because clozapine was discontinued before the post-treatment measurement of EEG or C-CLZ. Ultimately, 20 patients (6 men, 14 women) with an average age of 36 years were enrolled. The subjects were divided into EEG normal and abnormal groups. C-CLZ and N-CLZ were measured at 4, 12, 26, and 52 weeks after initiating CLZ administration.

Results: All patients had normal baseline EEG signals, and 8 patients showed EEG abnormalities later. There were significant correlations between C-CLZ and D-CLZ, and between N-CLZ and D-CLZ. The C-CLZ/D-CLZ, N-CLZ/D-CLZ, and C-CLZ/N-CLZ ratio were not significantly different between the EEG normal and EEG abnormal groups. The EEG abnormal group had significant higher proportion of patients with high intra-individual variability in their C-CLZ/D-CLZ ratio.

Conclusion: There is no relationship between C-CLZ and EEG abnormalities. However, patients with high intra-individual variability in their C-CLZ/D-CLZ ratio had greater possibility of exhibiting EEG abnormalities.

Keywords: Electroencephalography abnormalities; Serum clozapine concentration; Treatment-resistant schizophrenia.

Figure 1.

The time course of the C/D ratio for each patient from both groups. A: C/D ratio of the EEG normal group, B: C/D ratio of the EEG abnormal group. C/D: serum concentration of clozapine/daily dose of clozapine, EEG: electroencephalogram.