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

Abstract

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.