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The "revolution" in pharmacologic treatment of insomnia began in 1970 with the availability of flurazepam, the first of the benzodiazepine hypnotics. Flurazepam largely replaced all other hypnotics during the decade of the 1970s. The second revolution began in the early 1980s as shorter half-life hypnotics, triazolam and temazepam, became available and began to replace flurazepam. The decade of the 1990s will probably see a more balanced pattern of benzodiazepine hypnotic use, as well as use of newer nonbenzodiazepine hypnotics. Among available benzodiazepines, all have the capacity to produce dose- and concentration-dependent sedation, drowsiness, performance impairment, and amnesia. Benzodiazepine-induced amnestic effects are characterized by either impairment of information acquisition, impairment of consolidation and storage, or both. In general, apparent clinical differences among benzodiazepine hypnotics are explained by differences in pharmacokinetic properties of absorption, distribution, elimination, and clearance.

Insomnia is common in the elderly population. Difficulty in initiating and maintaining sleep affects nearly half of all patients over the age of 65, representing an increased prevalence in older versus younger patients. Nocturnal sleep time is decreased, frequent awakenings occur, and daytime napping is common. Age-related changes in sleep physiology correlate with the subjective complaints of disturbed sleep. Multiple etiologies for insomnia in the elderly have been described. Management strategies must include attention to both nonpharmacologic and pharmacologic aspects of care, especially with respect to the altered pharmacokinetics and pharmacodynamics associated with advanced age. Reassessing therapy is essential to promote the end goal of improvement of the elderly patient's quality of life.

Daytime residual drowsiness and psychomotor performance were assessed for two long half-life benzodiazepines, quazepam and flurazepam, in two randomized, parallel, and double-blind studies in insomniacs. Seventeen middle-aged patients took quazepam 15 mg or 30 mg, or flurazepam 30 mg; the 47-night study included 4 placebo baseline nights, 28 consecutive treatment nights, and 15 posttreatment nights. Forty-eight geriatric patients took either flurazepam 15 mg, quazepam 15 mg, or placebo; the 15-night study included 1 placebo baseline night, 7 treatment nights, and 7 posttreatment nights. The Multiple Sleep Latency Test (MSLT), an objective test for measuring daytime sleepiness, and performance tests were administered. In the first study, flurazepam patients were significantly (p less than .05) sleepier after the 7th and 14th treatment nights when compared to baseline, whereas quazepam patients were not. In the second study, flurazepam patients were sleepier at midday (p less than .10) and late afternoon (p less than .05) after 1 treatment week than were quazepam and placebo patients. Performance test results suggested quazepam has a relatively low potential for daytime impairment. Thus, quazepam 15 mg produces less daytime somnolence and fewer psychomotor performance decrements than does flurazepam.

Findings from a four-city study of the beneficial and adverse effects of hypnotics are reported. The study employed a new volunteer call-in method for monitoring drug effects outside of the clinical setting. Respondents were recruited through newspaper advertisements. They were invited to complete a short telephone interview if, during the past 12 months, they (1) had significant trouble with insomnia or (2) had taken a medication to induce sleep. Comparison groups were flurazepam, temazepam, triazolam, and over-the-counter (OTC) sleep medications. An untreated insomnia group also was included. Results indicate that most users of prescription hypnotics attributed positive effects to their sleep medications and that adverse effects were infrequent. OTC hypnotics were less effective and more likely to produce negative effects. The untreated insomnia group was more symptomatic than any of the medication groups.

There has been a paucity of research in the use of high-dose benzodiazepines in the treatment of severe neurotic anxiety. The author presents five cases, three with excellent and two with poor outcomes. The English and Fench language literature is reviewed and reveals evidence that high-dose benzodiazepines may be useful in the treatment of certain neurotic patients. However, the lack of controlled studies is noted. The author poses several questions important to the future of research on benzodiazepines.

The efficacy and safety of estazolam, an investigational triazolobenzodiazepine, and flurazepam were compared in 65 insomniac outpatients. Patients completed sleep questionnaires each morning. Global evaluations demonstrated that both treatments were significantly superior to placebo. However, estazolam was preferred over flurazepam in a global rating that reflected how well rested and refreshed the subjects felt on arising. Improvement in complaints of difficulty in going to sleep showed only a trend toward significance favoring estazolam and flurazepam over placebo. Residual daytime drowsiness and fatigue accounted for approximately 70% of all side effects with both active treatments. Significantly more side effects occurred with flurazepam than with estazolam. Flurazepam-treated patients had a significantly more severe rating of adverse reactions than did placebo-treated patients.

Insomnia and the use of long-acting hypnotic drugs are prevalent in geriatric populations. These drugs have been shown in the laboratory to adversely affect motor performance in the elderly. To examine the clinical significance of these findings, comparisons were made between patients who experienced a fall during their hospital stay and those who did not fall. It was found that patients over 70 years of age who experienced a fall in the hospital were more likely to be receiving flurazepam than the patients who did not fall.