Abstract
Olanzapine is structurally similar to clozapine but has not been shown at routine doses to share the superiority of clozapine to traditional antipsychotics in treatmentโresistant patients. Olanzapine, however, has been increasingly used in higher doses as clinicians attempt to find a more tolerable therapy for those refractory to conventional agents. This study examined the relationship of highโdose olanzapine plasma concentrations to symptoms, adverse effects, smoking, and gender. Thirteen patients participated in a double blind 16โweek crossover study (8 weeks each arm) of olanzapine (50โmg/day) compared to clozapine (450โmg/day). Women had significantly higher plasma olanzapine levels than men at each time point in each arm (weeks 4, 6, and 8). At 8 weeks women had a steadyโstate olanzapine level of 278โยฑโ62โng/ml while men had a steadyโstate level of 127โยฑโ47โng/ml (pโ=โ0.005). At week 4, olanzapine levels tended to be higher in those who had been on clozapine previously (205โng/ml) compared to those who received olanzapine in the first arm (105โng/ml). Cigarette intake was negatively correlated to olanzapine plasma concentrations (week 8: rโ=โโ0.86, pโ<โ0.05). Plasma levels were significantly higher in those experiencing constipation (176 vs. 82โng/ml; pโ=โ0.022). Plasma levels of olanzapine were not associated with symptom response and anticholinergic effects were seen at greater frequency with higher olanzapine concentrations. In conclusion, this study reports plasma olanzapine levels at high fixed doses of olanzapine (50โmg/day) in relation to side effects, symptoms, smoking, and gender. Copyright ยฉ 2006 John Wiley & Sons, Ltd.