Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interactions.

Ethanol and benzodiazepines interact both pharmacokinetically and pharmacodynamically. However, the importance of these effects has been exaggerated. Kinetically, acute doses of ethanol impair the disposition of benzodiazepines that are metabolized by demethylation or hydroxylation, but not those that undergo glucuronide conjugation. On the other hand, chronic ethanol administration increases the clearance of benzodiazepines that are demethylated or hydroxylated. The pharmacodynamics of the ethanol-benzodiazepine combination is less clear. The sedative and psychomotor effects of the combination appear to be enhanced, compared to the effects of the drugs given alone. However, it is difficult to assess the proportion of the observed effects that is due to benzodiazepines, as ethanol appears to be the dominant partner in this combination. Studies attempting to control for this imbalance have been so hampered by methodological problems that no firm conclusions can be drawn. Moreover, a number of benzodiazepines have not been studied in combination with ethanol. We suggest, however, that the ethanol-benzodiazepine interaction is probably less important than those involving ethanol and other psychotropic drugs, such as cannabinoids, neuroleptics, stimulants, and antidepressants.