Is chlordiazepoxide the rational choice among benzodiazepines?

Diazepam is frequently the subject of review by various agencies and institutions charged with determining whether or not to substitute another, more economical drug--in most instances, chlordiazepoxide. A review of the comparative literature has shown that, on clinical and pharmacokinetic grounds, chlordiazepoxide is not the drug of choice for all clinical indications recommended for the benzodiazepines as a class, particularly for use as an antianxiety agent. There is evidence that the antianxiety effect of chlordiazepoxide is related to the appearance of its two active metabolites, which may explain the observed delay in its onset of action. When chlordiazepoxide's reduced clearance in the elderly and in patients with liver disease is considered along with its limited range of indications, substitution of diazepam with chlordiazepoxide is clearly not reasonable. Diazepam and lorazepam are preferred choices in acute anxiety because they are themselves active anxiolytics. Oxazepam is recommended in alcoholic cirrhotics because its plasma clearance does not seem to be significantly affected by liver disease. Diazepam is recommended for chronic anxiety because of the rapid onset of action of diazepam itself and the smooth transition to the nondrug state via its longer-acting active metabolite.