CLOZAPINE PLASMA-LEVELS AND DOSING STRATEGIES IN PATIENTS WITH TREATMENT-REFRACTORY SCHIZOPHRENIA

Objective: To determine the effect on clinical response to clozapine o f increasing the plasma levels of clozapine and its major metabolite N -desmethylclozapine in 19 patients with schizophrenia who had plasma c lozapine levels less than or equal to 370ng/ml, a level previously det ermined to identify patients who were unlikely to have an adequate res ponse to clozapine. Method: The dosage of clozapine was increased by 2 0% in 11 patients and left unaltered in the other eight patients, Cloz apine and N-desmethylclozapine plasma levels were measured after six w eeks at the higher dose. Results: Nine of the 11 patients in whom cloz apine dosage was increased subsequently achieved plasma clozapine leve ls greater than or equal to 370ng/ml. However, in this group of patien ts who already had partially responded to clozapine, increasing the do sage of clozapine did not produce additional clinical improvement. Con clusion: Clozapine plasma levels are useful in clinical practice to gu ide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels greater than or equal to 370ng/ml is unlikely to produce further improvement in patients wh o have already achieved a partial response to clozapine at plasma leve ls less than or equal to 370ng/ml.