Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial

Clozapine is a drug with many side effects, some of them with potentially h azardous outcome (e.g. seizures, agranulocytosis), if not carefully monitor ed. It has been shown that the metabolism of clozapine may be affected by c oncomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatolo gy of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum co ncentrations of clozapine and its metabolites and the effect of this combin ation treatment on psychopathological outcome was evaluated. A total of 14 patients suffering from schizophrenia or schizodepressive disorder with pre dominant negative symptomatology were included. The duration of the study w as at least 6 weeks for each patient. Initial treatment was a monotherapy w ith clozapine at a daily dose of 2.5 mg/kg weight. After two measurements o f serum concentrations of clozapine and metabolites during steady state con ditions, an add-on therapy with 20 mg paroxetine was initiated. No concomit ant medication was allowed. The main finding of our prospective study was t hat addition of paroxetine to a monotherapy with clozapine was a well toler ated medication that did not give rise to new clinically relevant side effe cts. After addition of paroxetine the serum concentrations of clozapine and its major metabolites remained virtually constant. The results of the psyc hopathological measurements indicated a further clinical improvement, altho ugh the small open study could not test for efficacy. (C) 1998 Elsevier Sci ence B.V./ECNP. All rights reserved.