The relationship between clozapine dose and plasma level and side effects

Previous work has shown that monitoring clozapine plasma levels may help predict clinical response in treatment resistant schizophrenics, and that a threshold level exists above which clinical response rate increases. However there have been concerns that increasing the clozapine dose to achieve a higher plasma level may lead to higher rates of motor symptoms, or other side effects associated with neuroleptic use. In our study, 58 treatment resistant schizophrenic patients were entered into a fixed-dose, double blind trial. At week 4 half of the patients were treated with 400 mg and half with 800 mg. There was no difference in motor or other side effects between the two groups at week 4 and at week 12. Two patients developed seizures during the initial titration at oral doses of 200 mg a day. Furthermore, there was no relationship between side effects and clozapine plasma concentration.