Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged 65 years and over: data from a therapeutic drug monitoring service, 1996-2010

Objective To investigate the effect of dose and other factors on plasma clozapine concentrations in patients aged 65 years and over. Method Audit of clozapine therapeutic drug monitoring data, 1996–2010. Results There were 1930 samples [778 patients, 363 men aged (median, range) 67 (65–100) years and 415 women aged 68 (65–90) years]. There was no significant difference in the mean plasma clozapine concentration between men (0.56 mg/l) and women (0.58 mg/l), although the mean dose was higher in men (323 mg/d) than women (264 mg/d). The higher proportion of men (46%) compared with women (37%) smokers could explain this finding. Overall, 32% of samples had plasma clozapine below, and 37% above, a target range of 0.35–0.60 mg/l. Overall, the median dose decreased from 300 (65–70 years) to 200 mg/d (age 85 years and over). However, prescription of >350 mg/d was associated with a 50% likelihood that the plasma clozapine would exceed 0.60 mg/l. For a subgroup of 196 patients (114 men, 82 women), mean plasma clozapine was significantly higher after age 65 despite significantly lower dosage. Conclusion Clozapine dosage in elderly patients should be reviewed regularly to minimise the risk of adverse effects. Copyright © 2012 John Wiley & Sons, Ltd.