Dose versus Pharmacokinetics: Although use of a shorter acting benzodiazepine hypnotic will decrease the possibility of morning hangover, dose is of equal importance. All benzodiazepines given the night before can impair next-day performance. The longer half-life drugs produce more next-day performance impairment, but dose is the most important determinant. Use of shorter half-life drugs like triazolam may cause next-day impairment if doses of 0.5 mg are given, while doses of 0.125 and 0.25 mg greatly reduce next-day effects.
Rebound Insomnia and Memory Impairment: In the late 1980s and early 1990s, clinicians became aware that the benefits of a shorter half-life drug on next-day performance were countered by the increased risk of rebound insomnia and new memory impairment (anterograde amnesia) that was not commonly seen with the longer half-life drugs. These effects are also dose-related and can be minimized by use of the minimum effective dose consistent with appropriate clinician and patient expectations. Comparison of five benzodiazepine hypnotic agents found only the shorter half-life drugs to cause significant rebound insomnia.Rebound insomnia was defined as worsening of sleep compared to baseline. Triazolam in nightly doses of 0.5 mg caused rebound insomnia in each of four studies, was greatest the first night after withdrawal, and lasted from two to four nights.
Benzodiazepines can produce an impaired ability to store new memory while short-term memory is spared. The ability to use and remember previously acquired knowledge remains intact. The impaired ability to consolidate new memory seems to be independent of sedation. Anterograde amnesia is dose-related, seen more frequently with the higher potency benzodiazepines (e.g., triazolam, alprazolam, clonazepam, lorazepam, midazolam), and not dependent on elimination half-life. In addition, the elderly are more sensitive to this effect than are younger patients. There is also evidence to suggest that some tolerance develops to the sedative and psychomotor effects of benzodiazepines, but no tolerance develops to the anxiolytic and amnestic effects.