*Department of Psychiatry, University of Milan Medical School, 20161 Milan, Italy; **Department of Pharmacology, University of Milan Medical School, 20129 Milan, Italy; + Ravizza Clinical Research Laboratories, 20053 Muggio, Italy
The administration of long- and intermediate-acting benzodiazepines for the symptomatic relief of anxiety and mixed anxious-depressive syndromes is gen­erally viewed as safe and effective. Among the most widely prescribed anxiolytics in this country are chlordesmethyldiazepam (CDDZ), a derivative of diazepam’s major active metabolite with a half-life of about 83 hr in young adults (4), and alprazolam (APZ), a triazolobenzodiazepine with a half-life ranging from 11 hr in young males to 19 hr in elderly ones (10). Both drugs show the full spectrum of clinical and side effects of the classical minor tranquilizers and have been consistently shown to be more effective than placebo in the short- and long-term treatment of anxiety (1,8). The efficacy of the two compounds, however, has never been tested by direct comparison in a psychiatric population. As interest for newer and more selective anxiolytics grows, clinicians have shifted their attention from effectiveness against so-called target symptoms to a more solid concern for the short- and long-term sequelae of benzodiazepine administration (12). One of the most debated consequences regarding benzodiazepine hypnotics is the increase in daytime sleepiness above baseline levels. This has been both subjectively reported by patients receiving intermediate- and long-acting com­pounds in clinical doses, and objectively demonstrated for at least several days after the initial dose (5). Nonetheless, many anxious and anxious-depressed subjects appear to adapt quickly to the hypnogenic effect of anxiolytics, especially if the dose is slowly increased and well titrated against the more unpleasant symptoms. The intro­duction of standardized EEG laboratory techniques for the objective assessment of sleepiness, such as the multiple sleep latency test (MSLT) (6), however, has seriously challenged the reliability and accuracy of self-rated vigilance estimates (7). Some individuals seem to grossly over- or underestimate their capacity to maintain steady vigilance levels throughout the day. The inaccuracy seems par­ticularly evident in neurotic and anxious people who claim to be hyperalert even when taking sedative anxiolytics. In fact, subgroups of chronic insomniacs have been shown to have MSLT profiles similar to those of age-matched con­trols (14). Acute administration of hypnotic benzodiazepines produces daytime carryover effects that are dependent on the dose taken at night and on the pharmacokinetic characteristics of the compounds. Thus, the MSLT has been employed partic­ularly for the quantification of daytime residual effects on vigilance (9). It has been shown, for example, that short-acting hypnotics tend to produce less daytime somnolence than long-acting drugs (5). In fact, the MSLT can also be profitably applied for assessing the daytime somnolence of anxious patients who receive benzodiazepines exclusively during the daytime for the control of anxiety. This approach may be even more informative and clinically useful than the study of carryover effects since most anxious and anxious-depressed subjects need the anxiolytic effect, but not the excessive daytime sedation that causes a dramatic drop in their already reduced mental efficiency. In order to obtain a profile of daytime sleepiness in a target population, we have adopted the MSLT procedure in two groups of anxious middle-aged patients who were undergoing anxiolytic treatment with CDDZ and APZ.

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