The pharmacokinetic imperative in late-life depression

Older patients frequently have a high burden of medical illness, are subject to extensive medication regimens, and often experience adverse drug events. In general, pharmacokinetic changes associated with aging result in higher and more variable drug concentrations in older patients. Nonetheless, available information on pharmacokinetics of antidepressants is inadequate particularly with regard to medical subgroups and potential drug interactions. Although age-associated pharmacodynamic changes appear to make older patients more sensitive to side effects of antidepressants, differences in pharmacodynamics are not interpretable in the absence of drug concentration data. Population pharmacokinetics provides a means for assessing antidepressant drug exposure with relative ease and precision in clinical trials.