The effects of diazepam and diazepam/alcohol challenge on the performance in tests which examine aspects of driving ability of subjects who have been sub-chronically treated with a therapeutic dose of diazepam.

Subjects were given a maintenance dose of diazepam (5 mg) or an identical placebo tablet three times a day for 7 days. Their performance on a visual test battery was monitored before drug administration on day 1 and after a challenge dose of diazepam (10 mg or 0 mg), which was either given alone or in combination with a "social" dose of alcohol (0.75 g/kg). On day 8, the subjects were again tested on the visual test battery before and after a challenge dose of diazepam (10 mg or 0 mg) or diazepam/ alcohol. Venous blood samples were withdrawn and breath alcohol measurements were carried out prior to testing and at 60 and 90 minutes post-drug on both test days. Urine samples were collected on days 2, 4, and 6 to confirm compliance. Marked cumulation of both diazepam and its less active metabolite, N-desmethyldiazepam, was found in plasma by day 8. When alcohol was included in the challenge, the biotransformation of diazepam to N-desmethyldiazepam was reduced and the diazepam levels were higher than when the same dose of diazepam was given alone. These results agree with the findings for a single acute dose of diazepam. Although a degree of tolerance to the effects of a challenge dose of diazepam occurred in the diazepam-treated subjects by day 8, impairment was still evident after the second challenge. Significant impairment of performance was found for subjects given diazepam in combination with alcohol on both day 1 and day 8. This lack of tolerance to the psychomotor effects of the diazepam/alcohol challenge should be seen in sharp contrast to the subjective estimates of impairment reported by these subjects. They reported less sedation, an improvement in cognitive and coordinative ability and an increased willingness to drive even though their performance on some tests was worse on day 8 than on day 1. These findings suggest that drivers who commence therapy with diazepam and other benzodiazepines are likely to be impaired during the first week of treatment but may well be unaware of their reduced ability. The effects of even a modest dose of alcohol are likely to be exacerbated by diazepam treatment. (A)