HIGH PLASMA CLOZAPINE LEVELS IN TARDIVE-DYSKINESIA

Studies in the literature that attempt to relate neuroleptic plasma le vels to the development of tardive dyskinesia (TD) report inconsistent findings. As part of an open, long-term study, 60 schizophrenic and s chizoaffective patients were started gradually on a b.i.d. schedule of the atypical antipsychotic drug clozapine. Blood samples were drawn w eekly for 6 weeks and analyzed for a variety of constituents including clozapine plasma levels. Patients with higher levels of TD were found to have significantly higher levels of plasma clozapine and a higher ratio of plasma/dose than those with lower levels of TD. Our data sugg ests that schizophrenics with TD may have different pharmacokinetics, drug metabolism, and elimination processes than those without TD. High er typical plasma neuroleptic levels may increase susceptibility to TD development. A second hypothesis implies that it is not the higher me an plasma level of a neuroleptic that is associated with TD but the gr eater fluctuations of plasma levels over time (i.e., a higher variance ). This hypothesis is discussed in the context of our data.