Comparative anxiolytic and hypnotic effects of 3 benzodiazepines on baboons

The ECoG and behavioural effects of administering 3 benzodiazepines (diazepam, nitrazepam, lorazepam) were tested in baboons restrained in a chair, with arms fastened (a situation which is considered 'anxiogenic'). Considering our previous data with ECoG recording of focal rhythms from area somatic I, the 3 drugs were revealed as 'anxiolytic'. Differences were noticed with respect to their hypnotic effects: no sleep was elicited under diazepam; a considerable amount of slow sleep was observed with lorazepam; nitrazepam produced a succession of short waking/sleep cycles.     

The effects of hypnotic and nonhypnotic imaginative suggestion on pain

Background: Few studies have compared placebo and suggested pain reduction.Purpose: Hypnotic and nonhypnotic imaginative analgesia suggestions were compared against a placebo in reducing experimental pain. The mediator role of response expectancies and the moderator role of hypnotic and nonhypnotic imaginative suggestibility were evaluated.Methods: Sixty participants previously assessed for hypnotic and nonhypnotic imaginative suggestibility were assigned to one of two experimental conditions or a no-treatment control condition. In the “placebo first” condition, participants received placebo, followed by imaginative and then hypnotic analgesia suggestions. In the “placebo last” condition, participants received imaginative and then hypnotic suggestions, followed by placebo.Results: Imaginative and hypnotic suggestions did not differ significantly and were more effective than no treatment in reducing pain. The placebo was no different from the analgesia suggestions and was more effective than no treatment, but only when administered after the suggestions. Pain reduction was mediated by expectancy but was not significantly related to suggestibility or hypnotizability, the latter operationalized as hypnotic suggestibility with imaginative suggestibility statistically controlled.Conclusions: In the general population, nonhypnotic imaginative suggestions may be as effective as hypnotic suggestions in reducing pain. Response expectancies would seem to be an important mechanism of placebo and suggested pain reduction. We most gratefully acknowledge the dedicated assistance of Amanda Breen, Gina Carosella, Stephanie Hays, Tracy Poppe, Catherine Sullivan, and Casey Webster in the completion of this study. We thank Mary Alice Mills-Baxter for her helpful comments on a previous version of this article.     

Residual effects of temazepam and other hypnotic compounds on cognitive function

The morning after effects of taking single doses of three hypnotic compounds were compared in a five-group design, including the three drug conditions (temazepam, flurazepam, barbiturate), placebo, and no capsule controls. Results showed a slight superiority for temazepam over barbiturate on visual-motor and reaction time tasks. On one phase of a cognitive task, the barbiturate and flurazepam groups made more errors than the control groups. Overall, the results indicate an impairment in performance for the group taking barbiturate and a smaller impairment for the flurazepam group. No detectable impairment occurred for subjects taking temazepam.     

Comparative amnestic effects of benzodiazepine hypnotic agents

The effects of triazolam 0.5 mg and temazepam 30 mg on immediate and delayed recall in normal and insomniac subjects were evaluated in three separate, randomized, placebo-controlled, parallel group studies. Neither drug caused significant impairment of immediate recall. In the tests of delayed recall, triazolam caused a consistent anterograde amnestic effect. No significant impairment of delayed recall was observed in the temazepam study. Anterograde amnesia is thought to be a dose-related effect of benzodiazepines. Compounds with high benzodiazepine receptor affinity such as triazolam are thought to cause this type of amnesia more often than the lower-affinity compounds such as temazepam.     

Explorative single-blind study on the sedative and hypnotic effects of buspirone in anxiety patients

In this single-blind study the sedative and hypnotic properties of buspirone, a nonbenzodiazepine anxiolytic, were investigated in 8 anxious outpatients. Polysomnographic recordings were gathered during baseline, at the start of active medication, after 3 weeks of treatment and one night after discontinuing treatment. Daytime alertness was measured using the Multiple Sleep Latency Test and performance tests. The effects of buspirone on sleep structure were minimal and of no clinical consequence. Subjectively, the patients reported improved sleep quality. There were no effects on daytime alertness at the beginning, after 3 weeks or at sudden discontinuation of the medication. It is concluded that buspirone does not have a sedative or hypnotic effect in anxiety patients.     

Residual effects of repeated administration of triazolam and nitrazepam in healthy volunteers.

The residual effects of hypnotics were investigated with a long-acting (nitrazepam) and a short-acting (triazolam) benzodiazepine hypnotic in 8 male volunteers. Subjects received placebo, nitrazepam 5 mg, or triazolam 0.25 mg for 7 consecutive nights in a random-order, double-blind crossover design. Daytime sleepiness, psychomotor performance, EEG activity and standing steadiness were assessed in the morning after 1, 4, and 7 days of drug treatment. Plasma concentrations of nitrazepam and triazolam were also assayed. The concentration of nitrazepam increased gradually during the course of treatment and was associated with residual sedative effects on days 4 and 7. Nitrazepam produced no apparent psychomotor impairments in these studies. On the other hand, there was no evidence of drug accumulation after triazolam administration and triazolam showed no residual sedative effects or residual impairment of psychomotor performance during the experiment. Thus, short-acting hypnotics may have an advantage over long-acting hypnotics in terms of producing less residual sedative effects during chronic treatment.     

Acute neurophysiological effects of the hypnotic zolpidem in healthy volunteers

INTRODUCTION: The imidazopyridine zolpidem is a hypnotic drug with relative selectivity for the benzodiazepine (BZP) type 1 receptor subtypes displaying a different biochemical structure to that of BZPs. Little is known of its electrophysiological effects. PURPOSE: The aim of the present study was to investigate the acute neurophysiological effects of clinical oral doses of zolpidem. METHODS: This was a double blind, independent group design study. Thirty-six young, healthy volunteers were randomly allocated to one of three groups--zolpidem (5 mg and 10 mg) and placebo. In addition to ERPs, behavioural measures were used to examine sedative effects of the drug. RESULTS: ERPs were affected in a similar way to that described after sedative/hypnotic drug ingestion: increased N2 and P3 latencies and decreased N2 and P3 amplitudes. However, contrary to what is expected of a hypnotic drug, there was no change with N1 while P2 amplitude increased after the highest dose. CONCLUSIONS: Because zolpidem showed different effects in different components, it seems to first enhance or preserve initial orienting (no change in N1), after an increase of P2 and then drastically diminish resource allocation (affecting N2 and P3 latencies and amplitudes). The study with ERPs, therefore, allows a more direct "moment to moment" investigation of finer mechanisms of changes in cerebral processes underlying the acute ingestion of the drug in question. The effects on N2 and P3 amplitudes and latencies were similar to those of other sedative/hypnotic drugs. However, zolpidem led to an unexpected increase in P2 amplitude; this effect may be related to its selective receptor binding profile and warrants further research.     

The hypnotic effects of melatonin treatment on diurnal sleep in humans

This study investigated the hypnotic effects of 10 mg melatonin and placebo, which were administered at 10.00 h, according to a single-blind crossover design, on an 8-h diurnal sleep from 11.00 to 19.00 h, following a full night of sleep. The subjects were six healthy male students, each of whom underwent polysomnography and rectal temperature monitoring. Melatonin treatment significantly increased total sleep time in diurnal sleep (403.2+/-SD 72.8 min and 258.5+/-118.3 min, P<0.001). As to changes in rectal temperature during diurnal sleep, however, there were no significant differences between the melatonin and placebo conditions. Thus, these results indicated that melatonin administered at 10.00 h had direct hypnotic effects on diurnal sleep.