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.