EEG ALTERATIONS AND SEIZURES DURING TREATMENT WITH CLOZAPINE - A RETROSPECTIVE STUDY OF 283 PATIENTS

In a retrospective study, 1863 EEG recordings made during clozapine treatment of 283 patients with normal pretreatment EEG evaluations were analyzed. Furthermore, they were compared to the EEGs of the same patients without clozapine (i.e., during other neuroleptic medication). Moreover, the data of all patients who had seizures during treatment with clozapine were evaluated in case reports. Classical clinical EEG evaluation criteria for normal versus abnormal were used (including diffuse slowing and grouped alterations according to Jung 1953 and Kugler 1983). Of the 283 patients investigated, 61.5 % (174) showed at least one abnormal EEG under clozapine according to these criteria. Evaluating all recorded EEGs of these patients in order to get some longitudinal information, we found a rate of 53.4 % abnormal EEG recordings during clozapine treatment. Most of the EEG changes were evaluated as slight (22.5 %) to moderate (10.1 %) diffuse slowing and some as groups of non-paroxysmal waves (39.8 %) or sharp waves (16.2 %) rendering the EEGs abnormal according to the above criteria. Potential signs of increased bioelectrical cerebral reagibility such as paroxysmal activity (4.3 %) or severe diffuse slowing (0.2 %) were rare. A nearly linear correlation with the daily dose was found in the range up to 300 mg clozapine/day for both diffuse and grouped alterations. Possibly due to selection, adaptive mechanisms/habituation, and/or other unknown factors, the rate of alterations decreased slightly at doses above 300 mg and rose again sharply for doses over 600 mg/d. Three of the clozapine-treated patients, equivalent to 1.1 %, developed seizures. Factors, contributing to the seizures, might have been the clozapine medication between 75 mg and 400 mg daily, a preexistent cerebral injury, or the discontinuation of a diazepam treatment. There was no predictive information available in the preictal EEGs under clozapine, which shows that a clear distinction should be made between signs of increased bioelectrical cerebral reagibility under clozapine medication as measured by the EEG and an increased risk for seizures encountered clinically.