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.