Side-effect 'tolerance' in elderly long-term recipients of benzodiazepine hypnotics

The outcome of long-term benzodiazepine hypnotic therapy has been investigated in a group of elderly patients in the community; 220 receiving nitrazepam and 33 flurazepam. The estimated duration of therapy was as long as 15 years in some cases. More than half were taking doses greater than 5 mg and 15 mg, respectively, the majority on a regular nightly basis in accordance with the instructions on containers. The plasma concentrations of nitrazepam and the active desalkyl metabolite of flurazepam correlated positively with weight-related dose. In the case of desalkyl-flurazepam, but not nitrazepam, the levels were substantially higher than those previously reported in young individuals. There was sustained patient satisfaction with the effectiveness of the hypnotics and, despite the high plasma levels, little subjective or objective evidence of unwanted sedation, confusion or unsteadiness. The findings of the survey suggest the development of both pharmacodynamic tolerance to the unwanted sedative effects of these drugs and a degree of dependence in long-term recipients.