Neurocognitive evaluation and plasma clozapine concentrations in Chinese patients with treatment-refractory schizophrenia

Abstract

Clozapine has been shown to be effective in treatment-refractory schizophrenia for positive and negative symptoms as well as some neurocognitive dysfunction. Nineteen patients with treatment-refractory schizophrenia were recruited for a 3-month trial of clozapine. Clozapine was titrated against clinical response to a maximum daily dosage of 200mg, 400mg and 600mg in the first, second and third month respectively. Steady-state blood concentrations of clozapine, clozapine-Noxide and N-desmethylclozapine were determined at the end of each month. At baseline and the end of each month, patients were assessed by using Positive and Negative Syndrome Scales, High Royds Evaluation of Negativity, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression(severity & change) for their clinical symptoms and Abnormal Involuntary Movement Scale, Simpson-Angus Scale and Barnes Akathisia Rating Scale for the extra-pyramidal side effects. Neurocognitive function was assessed by applying Wisconsin card sorting, verbal fluency, digit spans, logical memory, visual memory, Stroop test, continuous performance test and Cambridge neurological inventory at baseline and at the end of the third month. Our results showed that 55.6% of the subjects responded at the end of the 3-month trial. The responders showed significant improvement in immediate and delayed logical memory and a trend of better performance in Stroop test at the end of the trial. The mean daily dosage for responder was 442.5mg (sd: 40.8) with blood concentration at 786.1 ng/ml (sd:118.2), 104.7 ng/ml (sd:12.0) and 570.1 ng/ml (sd:95.0) for clozapine, clozapine-N-oxide and N-desmethylclozapine respectively. The blood concentrations did not predicit clinical response. In conclusions, our study provides evidence for clinical efficacy of clozapine not only on psychopathology but also on memory and selective attention.