Clozapine plasma levels and dosing strategies in patients with treatment-refractory schizophrenia

Objective: To determine the effect on clinical response to clozapine of increasing the plasma levels of clozapine and its major metabolite N- desmethylclozapine in 19 patients with schizophrenia who had plasma clozapine levels ≤ 370ng/ml, a level previously determined to identify patients who were unlikely to have an adequate response to clozapine. Method: The dosage of clozapine was increased by 20% in 11 patients and left unaltered in the other eight patients. Clozapine and N-desmethylclozapine plasma levels were measured after six weeks at the higher dose. Results: Nine of the 11 patients in whom clozapine dosage was increased subsequently achieved plasma clozapine levels ≤ 370ng/ml. However, in this group of patients who already had partially responded to clozapine, increasing the dosage of clozapine did not produce additional clinical improvement. Conclusion: Clozapine plasma levels are useful in clinical practice to guide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels ≤ 370ng/ml is unlikely to produce further improvement in patients who have already achieved a partial response to clozapine at plasma levels ≤ 370ng/ml.