Pharmacoclinical strategy in neuroleptic resistant schizophrenic patients treated by clozapine: Clinical evolution, concentration of plasma and red blood cell clozapine and desmethylclozapine, whole blood serotonin and tryptophan

1. The aim of the study was to determine if a more rational therapeutic app roach could be devised for neuroleptic resistant psychotic patients treated for months and years with clozapine. Clozapine is an atypical antipsychoti c medication, but its therapeutic benefit has been limited by a high incide nce of agranulocytosis and seizures. 2. The study has been performed in an open setting and included 12 patients . Some of them developed a secondary depression and were treated with fluox etine. 3. Pharmacokinetic analysis were conducted at the same time as clinical eva luations, grading using the BPRS, the PDS, the QLS, and determinations of p lasma and red blood cell clozapine and desmethylclozapine, plasma and RBC f luoxetine and norfluoxetine, whole blood serotonin and tryptophan. 4. A positive linear correlation was found only between RBC concentration a nd the evolution of the QLS. 5. Clozapine is efficacious both on positive and negative symptoms but its mechanism of action remains unclear. Positive symptoms disappear more quick ly, sometimes followed by a post psychotic depression, Negative symptoms im prove more slowly but regularly. They seem to be correlated with serotonine rgic mechanisms. For whole blood 5HT, an important increase was seen about 4 weeks after Cloza administration, and then a decrease. 6. Therapeutic drug monitoring (on the same sample drawn for haematological monitoring providing) could play a useful role in the management of patien ts treated by clozapine : compliance, lowest dose, possible toxicity, drug interaction, lack of efficacy, relapse predictivity.