PurposeWe describe electroencephalography (EEG) abnormalities and seizures associated with clozapine treatment in Japanese patients with schizophrenia and retrospectively compare EEG results and total Positive and Negative Syndrome Scale (PANSS [T]) scores before and after treatment.MethodsTwenty-six patients with treatment-resistant schizophrenia were enrolled in this study. EEG measurements were obtained prior to clozapine treatment and every 4 weeks thereafter. EEG measurements were also obtained at the time of seizure. After seizures or EEG abnormalities were noted, additional EEGs were performed every 2 weeks. PANSS (T) scores were used to determine clozapine treatment outcome.ResultsAll 26 patients had normal baseline EEG measurements, and ten patients (38.5%) later manifested EEG abnormalities. The mean age was significantly lower than in the abnormal EEG group. Six patients (23.1%) experienced seizures. The mean dose of clozapine at the first occurrence of seizure was 383.3 mg/day. Five of six patients who experienced seizures in this study were successfully treated with valproate or lamotrigine without discontinuation of clozapine. The one patient who continued to experience seizures was successfully treated without antiepileptic drugs. The mean baseline PANSS (T) scores were not significantly different between the normal and abnormal EEG groups, but the mean score in the abnormal EEG group was significantly lower than that in the normal EEG group at the final follow-up (P=0.02).ConclusionEEG abnormalities may appear in younger patients, and our findings indicate that there is no need to discontinue clozapine when seizures occur. EEG abnormalities that appeared after clozapine treatment were associated with a good clinical response.

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IntroductionClozapine-induced electroencephalography (EEG) abnormalities are common. It has been reported that clozapine-induced EEG abnormalities occur in a dose-dependent manner and correlate with the serum concentration of clozapine (C-CLZ). However, the oppositional results were also reported.ObjectivesThe objective of this study was to investigate the relationship between serum level of clozapine and EEG abnormalities.MethodsTwenty-eight patients were recruited in this study, but five patients were excluded because clozapine was discontinued before post-treatment EEG measurement or measurement of C-CLZ. Ultimately, 23 patients (6 males, 17 females) with an average age of 35 years were enrolled. The subjects were divided into EEG normal and abnormal group. C-CLZ and the serum concentration of metabolite of clozapine (N-CLZ) were measured. The correlation between C-CLZ and daily dose of CLZ (D-CLZ), N-CLZ and D-CLZ were evaluated in each group. C-CLZ per D-CLZ (C/D), N-CLZ per D-CLZ (N/D) and the ratio of C-CLZ to N-CLZ (C/N) were compared between the two groups.Results74 serum levels were measured. All patients had normal baseline EEGs, and 10 patients later showed EEG abnormalities. There were a significant correlation between C-CLZ and D-CLZ (EEG normal: rs 0.58, p<0.01, EEG abnormal: rs 0.56, p<0.01) and between N-CLZ and D-CLZ (EEG normal: rs 0.53, p<0.01, EEG abnormal: rs 0.57, p<0.01). There were no significant differences between the EEG normal and EEG abnormal groups in C/D, N/D, C/N.ConclusionThere was no relationship between the serum concentration of clozapine and EEG abnormalities.