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The results of the study of hypnotic states on the basis of subjective reflections of their perceptions by patients are presented. The factor map of the features of hypnotic states formation is obtained and some variants of the course of hypnotic states are determined in light of domination of the certain factors.
In the present study, a hypnotic relaxation technique was compared to stimulus control and placebo conditions as a means of reducing sleep onset latency (SOL). Forty-five subjects (Ss) were matched on their baseline SOL as measured through sleep diaries. They were randomly assigned to one of three groups: hypnotic relaxation; stimulus control; and placebo. These groups experienced four weekly sessions of 30-minutes duration with demand effects being controlled through the use of counter-demand instructions. Data generated by the study suggested that the particular hypnotic relaxation treatment used was effective in helping Ss go to sleep more quickly. Neither stimulus control nor placebo groups recorded similar improvement.
Three experiments were conducted to determine the relationship between hypnotic susceptibility level and the susceptibility to several perceptual phenomena. Experiment I required subjects to observe an induced afterimage in a light-proofed environment and to report the frequency of direction and color changes. In addition, subjects reported the persistence of the afterimage. Experiment II involved the observation of a black dot against a white background, with frequency of observed movement being the dependent measure. Experiment III was similar to the second experiment except that the stimulus was encompassed by a frame. In Experiments I and II, subjects judged high in hypnotic susceptibility reported perceiving the strongest effect. This phenomenon was virtually eliminated in the third experiment. These results were interpreted as supporting a process whereby subjects judged high in hypnotic susceptibility are better able to selectively attend to relevant cues in a stimulus array during conditions of perceptual impoverishment.
The kinetic properties of three benzodiazepine hypnotics are reviewed. Flurazepam serves as a precursor for at least two rapidly appearing and rapidly cleared metabolites that may contribute to sleep induction and are nonaccumulating. The final metabolite of flurazepam (N-desalkylflurazepam), however, has a long half-life and accumulates during repeated dosage. Temazepam has a relatively slow rate of absorption and an intermediate half-life in the range of 10 to 20 hours. Triazolam has an intermediate rate of absorption; due to its ultrashort half-life (1.5 to 5 hours), triazolam is a non-accumulating hypnotic. Taken together with sleep laboratory studies and clinical trials, knowledge of the kinetic profile of benzodiazepine hypnotics can assist in evaluating their clinical benefits and disadvantages.
On the basis of his "cognitive behavioural alternative" view-point Barber has attempted to deny the hypnotic state as a psychophysical dimension necessary for the creation of recognised hypnotic behaviour. After an analysis of the definitions presented by those who believe hypnosis to be a "psychophysical state" and the contrary views of Barber, it is pointed out that both agree on its function, namely (hypnotic behaviour) = f (ideoplastic monoideism). The concept of hypnosis as "a special participatory state" (as defined in 1975), as a psychophysical state of being and acting in which focalised mental activity permits behaviour and experiences impossible in other conditions is therefore thought to be valuable.
The effect of anxiety-reducing hypnotic training on learning and reading-comprehension tasks was examined. Fifteen college students who reported having test-taking anxiety were randomly assigned to an experimental or a control group. The experimental group received hypnotic training to reduce anxiety prior to taking a learning and reading-comprehension test. No significant difference was found between the experimental and the control group on the simple-recall task. However, on the reading-comprehension test the experimental group scored significantly higher than the control group. Further examination of the total score revealed that the experimental group difference was due to superior performance on the inference items. There was no difference between groups on items that required the recall of information from the passage. These findings support the notion that hypnotic training may be useful to reduce anxiety and improve test performance.
Three experiments assessed the hypothesis that suggested amnesia for a previously learned word list is a function of subjects' interpretations of the ambigous aspects of the amnesia testing situation. By manipulating preliminary instructions concerning interpretations of this situation, subjects who were unselected with respect to hypnotic susceptibility were induced to show either substantial increments or decrements in amnesia. However, subjects high on hypnotic susceptibility ignored preliminary instructions and therefore could not be induced to show decrements in amnesia. Previous findings of more amnesia in hypnotic than in task-motivated subjects were both replicated and reversed by varying subjects' interpretations of the amnesia task. Analyses on the combined data from the three experiments confirmed earlier findings that partial amnesics tend to recall list items in a relatively disorganized fashion. All of these findings are consistent with an inattention hypothesis of suggested amnesia. Theoretical implications for hypnosis research are discussed.
Sedation is often justified in patients requiring colonoscopy. We investigated the potential usefulness of hypnotic relaxation in 13 women and 11 men (median age, 43 years; range, 22-67) for whom other forms of anesthesia were not available. Hypnotic relaxation resulted in moderate or deep sedation in 12 patients (nine women; p < 0.05). In the patients in whom hypnosis was successful, pain was less intense than in patients in whom hypnosis was unsuccessful (p < 0.001). In addition, all colonoscopies were completed in the successful group, versus 50% in the unsuccessful group (p < 0.05). The patients in the successful group all agreed to another examination under the same conditions, whereas only 2% in the unsuccessful group agreed (p < 0.001). Our study suggests that, in a subgroup of hypnotizable patients, hypnotic relaxation may be a safe alternative to drug sedation and merits further study.
In a double-blind controlled study, an oral dose of diphenhydramine hydrochloride (12.5, 25, or 50 mg), methapyrilene fumarate (36, 72, or 144 mg), or placebo was administered to 1295 post-partum patients if they complained of, or anticipated, a sleep problem. Hypnotic activity was assessed clinically by subjective and objective techniques. Methapyrilene and diphenhydramine, at all doses, were found to be effective hypnotics in comparison to placebo, based on sleep latency, sleep duration, awakening in the night, global evaluation, and morning alertness. Increasing the dose of these drugs, in the range studied, produced a minimal increase in effectiveness.
The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly assess and quantify a drug's side effects, whereas sleep laboratory studies are very limited in all of these areas. Sleep laboratory studies however provide a rigorous, precise, and comprehensive profile of a drug's activity since there is more control over experimental variables and measurements are objective as well as continuous throughout the night. These benefits offset the shortcomings of clinical trials, which include a lack of objective measurements, less control over experimental variables, failure to evaluate a drug's effectiveness with continued use, and inattention to drug interaction and withdrawal effect. Several basic principles derived from sleep laboratory findings have been incorporated into both the clinical trials and sleep laboratory evaluations recommended in the new FDA Guidelines for the Clinical Evaluation of Hypnotic Drugs. These principles include provision for adequate baseline and withdrawal periods, use of multiple consecutive drug nights to assess a drug's effectiveness with continued use, and inclusion of an adequate washout period when a cross-over design is used. The guidelines do not emphasize either clinical trials or sleep laboratory studies at the expense of each other, but rather stress their complementary utilization.
Salicylamide (SAM) can produce sedation and sleep in humans and animals. To explore the potential utility of the drug as a research tool for assessing disease effects on the response of the central nervous system to depressant drugs, and to obtain a better understanding of the clinically evident sedative action of SAM, studies were performed to characterize the relationship between the concentrations and hypnotic effect of this drug in rats. Female Lewis rats weighing 170-200 g received SAM by intravenous infusion at a rate of 0.49, 1.22, or 2.47 mg/min until the onset of loss of the righting reflex. This well-defined pharmacological endpoint occurred from 16.7 +/- 2.3 min (fastest infusion rate) to 110 +/- 27 min (slowest infusion rate) after the start of the infusion. SAM concentrations at that time in serum, serum water, brain, and cerebrospinal fluid (CSF) were similar in animals that had received the 1.22- or 2.47-mg/min infusion and lower in animals that were infused at a rate of 0.49 mg/min. The slowest infusion rate group also exhibited increased serum protein binding of the drug. The SAM concentration ratio, CSF-serum water, was essentially unity in all three groups, indicative of rapid equilibration of the drug across the blood-CSF barrier. Gentisamide, the hydroxylated metabolite of SAM, was found in serum, CSF, and brain, but in low concentrations at which this metabolite alone had no hypnotic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Over the last 20 years standardized techniques have been employed for the investigation of intravenous hypnotics, psychotropic and neuroleptic drugs. Sleep has been studied with the help of EEG measures and side-effects have been evaluated by psychometric tests. The EEG is a proven parameter with regard to dosage determination and as objective means to find sleep-inducing quantities of drugs. By means of vigilosomnograms we have established dose-effect curves and have made comparisons between related drugs in the form of equivalence studies. From an anaesthesiological point of view controllability of a substance is determined by duration of effect (short- or long-acting) and by depth of sleep (light or deep states) achieved. By these criteria midazolam displays good controllability with regard to duration, but not in terms of depth of sleep, since it follows the "all-or-nothing" rule, even with 0.1 mg/kg following both intravenous or intramuscular injection. Lormetazepam, on the other hand, shows good controllability of depth of sleep from tranquillity via sedation to hypnosis, but duration of effect is less well controllable in that patients remain lightly asleep even after 2 h. According to the vigilosomnograms the lormetazepam/oxygen/nitrous oxide combination produced a super-added increase in the depth of the hypnotic effect. After droperidol the specific nitrous oxide component of the depth of sleep at Bo stage was not exceeded. The development of benzodiazepine antagonists, which immediately counteract the benzodiazepine induced sleep and respiratory obstruction is a milestone in the area of CNS research.
Sleep can be measured by subjective ratings, electrophysiological recordings and by the physiological and biochemical changes occurring with sleep. Using these methods, we can select those who rate their sleep as unsatisfactory and those who feel fully satisfied by their sleep. Electrophysiological recordings of sleep show that there are relatively small differences between these good and poor sleepers: poor sleepers sleep less than good sleepers, but not as little as they think. However, the complaints of poor sleepers that they feel unrestored by their sleep should not be dismissed, for investigations employing the tools of physiology and biochemistry have revealed differences between good and poor sleepers that suggest that the sleep of poor sleepers may indeed be less restorative. The actions of hypnotic drugs on sleep can be similarly investigated. Preliminary findings suggest that hypnotic drugs may reverse some of the detrimental metabolic concomitants of poor sleep.
Drug plasma levels of N-desmethyldiazepam (10 and 20 mg/day given at night) and amylobarbitone sodium (200 mg/day given at night) were determined in 45 patients after 1 and 7 days of treatment together with estimates of hypnotic and residual effects. No relationships were found between clinical rati ngs of hypnotic effect and drug plasma levels, while significant correlations were observed between some performance taska and drug plasma concentrations of amylobarbitone sodium, and of the higher dose of N-desmethyldiazepam.
Data on subjective estimates and polygraphic measures of total sleep time and sleep latency were collected from the literature and analyzed for accordance or discrepancy between subjective and objective (EEG-based) mean values in experiments on acute treatment of insomnia by benzodiazepine hypnotics. In baseline placebo conditions there was a tendency to overestimate the disturbance of sleep. After drug administration, sleeping was overestimated. Within both subjective and objective measures, the magnitude of drug effects was correlated with poor initial sleep. If discrepancies between subjective and objective measures per se were analyzed, a number of correlational factors led to the hypothesis that psychological characteristics of a given population play a primary role: populations overestimating their sleep disturbances also tended to overestimate hypnotic drug effects. However, overestimations of drug effects were not correlated with type of drug or objective measures of sleep disturbance before treatment.
Benzodiazepine (BZP) hypnotics are now classified into four groups according to their plasma elimination rates: ultrashort-, short-, intermediate-, and long-acting drugs. Since the specific binding affinities for the BZP receptor vary widely among the BZPs and their active metabolites, it may be more reasonable to correlate their pharmacological activities with the BZP receptor occupancy rather than with their plasma concentrations. The time courses of total plasma concentrations of BZPs and their active metabolites after a single oral administration were obtained from the literature, and their unbound concentrations (Cu) were calculated from the reported values of their plasma unbound fractions. The data of the receptor binding affinities of the BZPs, reported as dissociation constants (Kd) determined by in vitro binding experiments, were also obtained from the literature. Using these values, the time courses of receptor occupancies [Cu/(Kd + Cu) x 100%] were calculated for the various BZPs. A mutual competitive inhibition was considered in the case of the drugs that had active metabolites. Although plasma total and unbound concentration time profiles of the BZPs showed a wide variation, similar patterns were obtained for the time courses of the receptor occupancy among the BZPs in each group, indicating that the BZP hypnotics can be classified more conveniently based on receptor occupancy theory.
Guaiacol Glyceryl Ether (GGE) is well known as an expectorant in a large number of cough syrups etc. More recently it was used in surgery because of its activity as a muscle relaxant and its additive effect on narcotics. Today many of the sedatives and hypnotics in the BRD, which are available without prescription, contain GGE in doses of 50 mg to 250 mg partially combined with other sedative acting substances. With regard to the abuse of sedatives and hypnotics GGE therefore will be more important in future. The analytical data of GGE (for details see key words), extraction behavior and identification of TLC combined with quantitative determination by HPLC are described.
The sedative, amnestic, and performance disruptive effects of benzodiazepine (Bz) receptor selective and non-selective hypnotics were studied in 23 healthy, normal subjects, aged 26.8 +/- 1.0 years. Triazolam (0.25 and 0.50 mg), zolpidem (10 and 20 mg) and placebo were administered, double-blind, at bedtime in a repeated measures design. During an awakening 90 min later (at approximate peak concentration of each drug) a 30-min performance battery which included memory, vigilance, and psychomotor tasks was completed. Each drug and dose impaired memory (both immediate and delayed), vigilance, and psychomotor performance relative to placebo. Among active drugs impairment was greatest with zolpidem 20 mg, next triazolam 0.50 mg, then zolpidem 10 mg, and finally triazolam 0.25 mg. Next morning delayed recall was also impaired by all drugs and doses (i.e. anterograde amnesia). The amnestic and performance-disruptive effects paralleled the relative hypnotic effects of the drugs and doses. No receptor selectivity in these pharmacodynamic effects was observed.