Development of tolerance and cross‐tolerance to the psychomotor actions of lorazepam and diazepam in man.

Abstract

1 Development of tolerance and cross‐tolerance to lorazepam and diazepam in man was assessed in a double‐blind and cross‐over trial where eight pretrained healthy students volunteered for four 1 week treatment periods started at 1 month intervals. 2 In each period acute psychomotor responses to oral lorazepam 3 mg and diazepam 15 mg were recorded on day 1, as well as on day 8 after 1 week's treatment twice daily with diazepam 5 mg, lorazepam 1 mg, and placebo. At each session several objective psychomotor tests and subjective assessments were done before the drug intake and 1, 2.5, and 4 h after it. 3 In general, the effects of lorazepam were stronger and of longer duration than those of diazepam at the doses used. When comparing the single‐dose responses on days 1 and 8, tolerance to lorazepam effects and some cross‐tolerance developed on several functions measured. Tolerance but not cross‐tolerance developed on choice reaction errors whereas the opposite was found on flicker fusion. No definite tolerance was found on subjective effects. 4 The results tally with an assumption that tolerance to benzodiazepine actions develops at different rates on various parameters measured.