Differential pharmacokinetics of lithium in elderly patients

The pharmacotherapeutic use of lithium in the elderly as acute and maintena nce therapy in bipolar disorder and augmentation therapy for major depressi on is well documented. Differences in the response to lithium are explained , in part, by the effect of age-related physiological changes, comorbid con ditions, and concurrent medications on the pharmacokinetics of lithium in t he elderly. The pharmacokinetic profile of lithium has been studied for man y years, primarily in younger adult populations. Lithium pharmacokinetics m ay be influenced by a number of factors including age. It was first noted s everal years ago that elderly individuals required lower doses of lithium t o achieve serum concentrations similar to those observed in younger adults. This is due to the combination of a reduced volume of distribution and red uced renal clearance. The composition of the human body changes with aging producing an increase in body fat, a decrease in fat-free mass and a decrea se in total body water. Lithium clearance decreases as the glomerular filtr ation rate decreases with increasing age. The effects of other medical conditions in the elderly on the pharmacokinet ics of lithium are less well delineated. Reduced lithium clearance is expec ted in patients with hypertension, congestive heart failure or renal dysfun ction. Larger lithium maintenance doses are required in obese compared with non-obese patients. The most clinically significant pharmacokinetic drug interactions associate d with lithium involve drugs which are commonly used in the elderly. Thiazi de diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs can increase serum lithium concentrations. The tolerability of lithium is lower in the elderly. Neurotoxicity clearly occurs in the elderly at concentrations considered 'therapeutic' in general adult populations. There are no placebo-controlled randomised trials of li thium in old age and recommendations for clinical use are based on extrapol ations from pharmacokinetic studies, anecdotal reports from mixed age popul ations and clinical experience in old age psychiatry. Serum concentrations of lithium need to be markedly reduced in the elderly population and partic ularly so in the very old and frail elderly.