Background: The changes of theta activity (3.5-7 Hz) in the quantitative electroencephalography (QEEG) and serum clozapine levels and their correlation with clinical response, measured by the Positive and Negative Syndrome Rating Scale (PANSS) for schizophrenia, were examined prospectively in 16 patients suffering from schizophrenia during 18 weeks of clozapine (CLO) treatment. Methods: Evaluations were performed on five occasions: before the initiation of CLO treatment at baseline and after 1, 3, 10, and 18 weeks of treatment. Doses of CLO starting from 50 mg/day were determined on the basis of clinical response. In the PANSS subscales for positive and negative symptoms, a significant (P < 0.05) improvement was observed after the first week, and in the subscale for general symptoms, improvement was seen after three weeks of treatment with CLO. A significant increase in theta power (P < 0.01) was found after three weeks of CLO treatment in the electrodes over the fronto-central scalp area, most distinctly in the midline. Results: After three weeks we observed 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 10 weeks, between the theta power increase and the change in PANSS subscales for general (P < 0.05) and positive (P < 0.05) symptoms. 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. Conclusions: These findings indicate that the change in the theta frequency in QEEG and particularly in the midline electrodes over the fronto-central scalp area might be a more sensitive indicator for the evaluation of CLO treatment adequacy than the serum CLO level.
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