Higher plasma drug concentration in clozapine-treated schizophrenic patients with side effects of obsessive/compulsive symptoms

Clozapine-induced obsessive/compulsive symptoms (OCS) have been reported by many authors. This study investigated the incidence of these side effects, together with the relation between these side effects and the plasma concentration (Cps) of clozapine and its metabolites norclozapine and clozapine-N-oxide in schizophrenic patients. One hundred and two schizophrenic patients treated with clozapine were interviewed and screened with questionnaires testing for OCS during a 1-year study period. Cps of clozapine and the metabolites were monitored using reversed-phase high-performance liquid chromatography with ultraviolet detection. Thirty-nine patients (38.2%) presented with OCS, and, of these, 29 patients (28.4%) were classified as clozapine-induced, with an average latent period of 39.8 +/- 22.5 months. The Cps of clozapine and norclozapine were significantly higher in patients with OCS than in those without (595.1 +/- 364.9 vs. 433.5 +/- 252.8 ng/mL, P = 0.001 and 266.4 +/- 144.4 vs. 203.1 +/- 119.8 ng/mL) OCS. Clozapine-induced OCS were not uncommon side effects. The authors suggest that the emergence of these side effects may be related to higher Cps of clozapine and clinicians should routinely check for and manage these side effects.