Methodology required to show clinical differences between benzodiazepines

Abstract

Clinical differences exist between the benzodiazepines but demonstration of such differences requires a more specialized methodology than that normally used in comparative trials. It is recommended that double-blind studies should be carried out in hospitalized patients with severe and chronic anxiety, selected according to precise criteria, and that the trials should be designed as crossover rather than as parallel group studies, with randomization of the stages and flexible dosage. A simple graphic method of representing the clinical profile of individual benzodiazepines is described and it is suggested that this could help clinicians adapt their prescribing to each patient's symptoms.

Self-Reports of Anxiety Level and EEG Changes after a Single Dose of Benzodiazepines

“…46. and 17 mm (on a total of 1,000) on the visual analogue scales, corresponding to a Pearson corre lation coefficient of 0.96 (p < 0.005) for Hamilton Anx iety Scale and 0.998 (p < 0.001) for the visual analogue scales. The use of crossover design decreases the coeffi cient of variation and allows a direct comparison of the clinical and EEG effects of the two compounds [Kellner ex al., 1978;Ansseau et al, 1984], This methodology per mits one to obtain significant conclusions with a limited number of subjects, as shown in this study.…”

Sedative premedication before surgery – A multicentre randomized study versus placebo

“…When patients were asked if they had perceived any sizeable effect after taking the two capsules, the effect of premedication (median 2, IQR [1]) was rated significantly greater than that of the placebo (median 1, IQR [1]) (p < 0.001), and the effect of the hypnotic (median 2, IQR [1]) was perceived to be greater than the placebo (p < 0.01). Interestingly, 28 patients (38%) in the placebo group felt relaxed by these non-active capsules.…”

“…Hence, oral premedication the day of surgery requires alternative drugs. We chose Alprazolam which has a high anxioselective activity and an acceptable 10 h half-life [1]. It compares well with midazolam for this purpose [2] and has gradually imposed itself for premedication among anaesthetists.…”

Premedication with Oral Alprazolam and Melatonin Combination: A Comparison with Either Alone—A Randomized Controlled Factorial Trial

“…Benzodiazepines are reported to be paradoxically associated with the increased episodes of arousal during sleep, restlessness, and hangover effects [2]. Alprazolam, a benzodiazepine class of antipsychotic drugs, is more anxioselective than the other premedicants of this group like midazolam, lorazepam, or diazepam [3]. It has also been reported to show arousal episodes [2].…”