Benzodiazepine hypnotics in the elderly

A review is presented of the changes that occur in the pharmacodynamics of benzodiazepines during normal ageing and as a result of disease. Controlled studies in which subjects of different ages have received single doses of diazepam, temazepam, nitrazepam and flunitrazepam have consistently shown an increase in the response to benzodiazepines in the elderly which is not explained by the effects of disease or by altered plasma concentrations. In general, healthy elderly subjects have a 2-3 fold greater response compared with the young. This change appears to be due to a change in the post-receptor mechanism of action. Cerebral diazepam concentrations are similar in young and elderly rats, though older animals also show an increased response and no consistent changes have been demonstrated in brain receptor binding. However, benzodiazepine-induced increases in GABA binding and GABA-induced increases in post-synaptic inhibition have been reported to be greater in aged animals. Regular daily dosing with most benzodiazepines leads to drug accumulation which is proportional to the elimination half-life. Regular dosing with diazepam, chlordiazepoxide, nitrazepam and flurazepam has also been found to produce more sedation in the elderly, particularly long stay patients who have a high incidence of dementia, and those with a low albumen or chronic renal failure. A controlled trial of 1 week's dosing with 5 mg of nitrazepam or 20 mg of temazepam in elderly in-patients showed that these doses produced significant impairment of psychomotor performance the morning after the last dose. Only about 50% of the patients were affected and many of these were frail patients with mild dementia on rehabilitation or long stay wards. The doses prescribed for these types of patients should not exceed 2.5 mg of nitrazepam or 10 mg temazepam.