To the Editor.—Dr Ray's1
Editorial that accompanies the article by Dr Hemmelgarn and colleagues2suggests that the common use of many of the short-elimination
half-life benzodiazepines as hypnotics in the elderly may account for the
lack of an association between these drugs and risk of injurious motor vehicle
crashes. After bedtime administration, peak plasma-drug concentrations would
occur at night. Thus, sleeping patients avoid the drug-associated cognitive
and psychomotor impairments. Rapid drug elimination would result in minimal
next-day effects. Ray1cautioned that daytime
use of these drugs as anxiolytics, as with longer half-life drugs, would result
in peak pharmacological actions during the day and possible increased risk
of injurious motor vehicle crashes. Hemmelgarn et al2
did not indicate whether benzodiazepines with relatively short half-life were
preferentially used as hypnotics rather than anxiolytics. Thus, lack of observed
association between these drugs and driving-crash risk remains unexplained.
Although next-day impairment associated with long half-life benzodiazepines
such as diazepam is well established,3few
studies have examined shorter half-life drugs.
Changes from baseline for the standardized mean-of-all-tests (Buschke
Selective Reminding Test Total Recall, Delayed Recall, and Intrusion Errors;
Discriminant Reaction Time; Critical Flicker Fusion) for the 5 parallel treatment
groups. A shows the effects of acute single doses at initial challenge; B,
the next-day effects after 1, 2, and 3 weeks of long-term, twice-daily treatment;
C, the effects of acute single doses at rechallenge after 3 weeks of long-term,
twice-daily treatment. Asterisk indicates P<.05;
dagger, P<.001; and double dagger, P<.01, for comparison of drug vs placebo.
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