A STUDY OF THE EFFECTS OF LONG-TERM USE ON INDIVIDUAL SENSITIVITY TO TEMAZEPAM AND LORAZEPAM IN A CLINICAL POPULATION

Aims The central effects of benzodiazepines may be attenuated after ch ronic use by changes in pharmacokinetics, pharmacodynamics or both. Th is attenuation may be influenced by the dosing pattern and the charact eristics of the user population. The objectives of this study were to evaluate drug sensitivity in long-term users of temazepam and lorazepa m in a clinical population. Methods The sensitivity to benzodiazepine effects in chronic users (1-20 years) of lorazepam (n=14) or temazepam (n=13) was evaluated in comparison with age and sex matched controls. Drug sensitivity was evaluated by plasma concentration in relation to saccadic eye movement parameters, postural stability and visual analo gue scales. Results Pharmacokinetics of lorazepam and temazepam did no t differ between patients and control subjects. Chronic users of loraz epam showed clear evidence of reduced sensitivity, indicated by lack o f ally pharmacodynamic difference between patients and controls at bas eline, when drug concentrations were similar to the peak values attain ed in the control subjects after administration of 1-2.5 mg of lorazep am. In addition, there was a two-to four fold reduction in the slopes of concentration-effect plots for measures of saccadic eye movements a nd body sway (all; P less than or equal to 0.01). By contrast, sensiti vity in chronic users of temazepam was not different from controls. Th e difference between the temazepam and the lorazepam group appears to be associated with a more anxious personality traits that were observe d in the chronic users of lorazepam. Conclusions Chronic users of lora zepam show evidence of tolerance to sedative effects in comparison wit h healthy controls. Tolerance does not occur in chronic users of temaz epam. The difference may be related to pharmacological properties, in addition to different patterns of use, associated with psychological f actors.