CLOZAPINE SERUM LEVELS AND SIDE-EFFECTS DURING STEADY-STATE TREATMENTOF SCHIZOPHRENIC-PATIENTS - A CROSS-SECTIONAL STUDY

Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and outpat ients on a variable dose regimen. All patients were in steady state wi th respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquart ile range in parenthesis) was 350 (228-425) mg/24 h (range 100-700). T here was a weak positive correlation between doses and the BPRS total score (r = 0.44, P < 0.05). The median S-Cloza was 1076 (706-1882) nmo l/l (range 196-5581 corresponding to 64-1824 ng/ml). The S-Cloza was l inearly correlated to dose but with a high interindividual variation a t equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindiv idual variability of 20%. The S-Descloza averaged 77% of the S-Cloza a nd was highly correlated to S-Cloza (r = 0.90; P < 0.001). The S-Descl oza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), in creased liver enzyme activity (60%), orthostatic hypotension (17%), an d moderate leucocytosis (17%). Only EEG changes were correlated to S-C loza (r = 0.43; P < 0.05). The score values of the UKU Side Effect Sca le were weakly (r = 0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indi cating a correlation between doses or S-Cloza and the frequency of sid e effects. It is concluded that clozapine fulfils the criteria for the rapeutic drug monitoring. TDM may contribute to finding the lowest eff ective dose with the fewest possible side effects.