Clozapine induced QEEG Changes Correlate with Clinical Response in Schizophrenic Patients – A Prospective, Longitudinal Study

The changes of theta activity (3.5–7Hz) in the quantitative electroencephalography (QEEG), serum clozapine (CLO) levels, and their correlation with clinical response, measured by the Positive and Negative Syndrome Rating Scale for schizophrenia (PANSS), were examined prospectively in 16 patients suffering from schizophrenia during 18 weeks of CLO treatment. Evaluations were performed in 5 occasions: before the initiation of CLO treatment at baseline and after one, three, ten, and eighteen weeks of treatment. Doses of CLO starting from 50mg/day were determined on the basis of clinical response. In the PANSS subscales for positive and for negative symptoms a significant (p<0.05) improvement was observed after the first week and in the subscale for general symptoms after three weeks of treatment with CLO. A significant increase in the absolute theta power (p<0.01) was found after three weeks of CLO treatment in the electrodes over fronto-central scalp area, most distinctly in the midline (FpZ, Fz, Cz). After 3 weeks there were significant inverse correlations between the theta power increase and the changes in PANSS subscales for negative (p<0.01) and positive (p<0.05) symptoms and after the 10 weeks between the absolute theta power increase and the change in PANSS subscales for general (p<0.05) and positive (p<0.05) symptoms observed. After 18 weeks a trend of inverse correlation between the PANSS subscales for general and negative symptoms and the right and midline theta power increase was observed, but not with regard to positive symptoms. There were trends but no significant correlations between CLO treatment response and serum CLO levels. These findings indicate that the change in the absolute theta power in the midline electrodes over fronto-central scalp area in QEEG might be a more sensitive and specific indicator for the evaluation of CLO treatment efficacy than the serum CLO level.