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A Comparative Study of the Interaction of Alcohol with Alpidem, Lorazepam and Placebo in Normal Subjects

Twelve healthy volunteers took part in a double-blind, cross-over comparison of the effects of lorazepam and alpidem on a battery of physiological, psychomotor and subjective tests before and after alcohol. Each subject received each treatment for 8 days and alcohol was given on day 8. Tests were carried out on days 1 and 4 and on day 8 before and after alcohol. Before alcohol the effects of alpidem on most tests were generally similar, but considerably less marked than those seen with lorazepam. There were some interesting differences between the two drugs in the effects on EEG and memory. In line with the effects seen with other anxiolytic drugs, lorazepam decreased the amplitude of auditory evoked potential. In contrast, alpidem was associated with an increase or a significantly smaller decrease. This suggests that there is no attenuation of input or central processing of the auditory stimuli. Both lorazepam and the higher dose of alpidem (50mg) reduced the number of words recalled but the lower dose of alpidem (25 mg) had significantly less effect on both immediate and delayed recall. These differences persisted after alcohol. On most of the tests the depressant effects of the drug before alcohol were enhanced after alcohol. However, the depressant effects of alcohol combined with active drug were in general no greater than those with alcohol with placebo, suggesting some degree of cross-tolerance.