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Biomedical subjects

W B Mendelson

Publications and source records attributed to W B Mendelson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of parenterally administered triazolam on sleep in rats with lesions of the preoptic area.

In previous work we have reported that microinjections of triazolam or pentobarbital into the medial preoptic area of the anterior hypothalamus produce a hypnotic effect. This finding raised the possibility that the sleep-enhancing actions after systemic administration of these compounds might be mediated by hypnogenic mechanisms in the preoptic area. The current study examined whether sleep enhancement by triazolam requires the anatomic integrity of the preoptic area. Nine rats with histologically confirmed lesions of the preoptic area induced by ibotenic acid (2.5 microg/microl in 0.4 microl), and 10 rats that had undergone a sham lesion procedure, had 2-h sleep studies that confirmed that by day 5 measures of total sleep time and sleep latency had returned to preintervention values. Rats were then given triazolam 0.8 mg/kg or vehicle intraperitoneally in counterbalanced order, on days 7 and 9 postlesion, in an environment with an ambient temperature of 25 degrees C. Following injections at 1000 h, in conditions in which lights were on from 0800-2000 h, 2-h sleep studies were performed. In the lesioned rats, triazolam significantly decreased sleep latency and increased total sleep time, primarily by increasing NREM sleep, whereas injections of vehicle did not. In summary, parenterally administered triazolam was found to have hypnotic effects in rats who were 1 week post-preoptic area lesion. These data are interpreted in light of previous evidence of redundancy of sleep-regulating mechanisms in the nervous system.

Animals↗
PubMed1998

Insomnia, health-related quality of life and healthcare resource consumption. A study of managed-care organisation enrollees.

OBJECTIVE: Insomnia is a prevalent sleep complaint which has been reported to be greatly associated with reduced health-related quality of life (HR-QOL) and increased healthcare resource use. This study documents the prevalence of insomnia, and its impact on patients' HR-QOL and healthcare resource use in managed-care settings in the US. DESIGN AND SETTING: A multi-site survey of 5 American Medical Group Association (AMGA) clinics was conducted. Each clinic mailed questionnaires to 1100 randomly selected individuals enrolled in its healthcare system and distributed questionnaires to 400 individuals during a clinic visit and prior to seeing a physician. The questionnaire was a form of the Health Status Questionnaire with the well-validated Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, a 3-question depression screen, a sleep questionnaire, demographic variables, and questions about medical encounters and prescription and over-the-counter (OTC) drug use. MAIN OUTCOME MEASURES AND RESULTS: Approximately one-third of managed-care enrollees in this study reported insomnia with daytime dysfunction. Individuals with insomnia reported lower HR-QOL scores and increased healthcare resource use compared with individuals with no insomnia. After controlling for demographic variable and comorbid conditions, the negative association of insomnia remained significant on all HR-QOL scores, emergency room visits, calls to the physician and OTC drug use. CONCLUSIONS: Insomnia is significantly associated with reduced HR-QOL and increased healthcare resource use in enrollees of managed-care organisations.

Health Care Surveys↗
PubMed1998

Prevalence of insomnia: a survey of the enrollees at five managed care organizations.

The purpose of the study was to assess the prevalence of and factors associated with insomnia among enrollees of managed care organizations (MCOs). A survey was distributed either by mail or during a clinic visit to 7,500 enrollees of five MCOs in the United States. The survey included a sleep questionnaire, demographic questions, and questions about medical encounters and prescription drug use. Three levels of insomnia (none; level I--difficulty initiating or maintaining sleep; level II--insomnia with daytime dysfunction) were defined from the responses. Comorbidities were determined by proxy from prescription drug use reported by respondents. A total of 3,447 survey responses were received, yielding a response rate of 46%. Level I and level II insomnia was reported by 13.5% and 32.5% of the respondents, respectively. Level II insomnia increased with decreasing education, income, and age and was more prevalent in women and non-Caucasians. Insomnia was significantly correlated with all daytime sleepiness and most nighttime disturbances factors. Fifty-two percent of all respondents reported at least one comorbid condition. Respondents with multiple comorbidities reported level II insomnia more frequently than those with no comorbidities. Only 0.9% of clinic visitors were seeing a physician specifically for sleep problems. Of those with level I and level II insomnia, only 5.5% and 11.6%, respectively, were taking prescription medications specifically for sleep problems; 11.2% and 21.4%, respectively, were taking over-the-counter medications for sleep. Insomnia occurs in MCO enrollees at rates comparable to those found in the general population. However, few patients with insomnia are actually being treated for their condition. Proper evaluation, diagnosis, and treatment of insomnia are warranted.

Adult↗
PubMed1997

Disordered sleep and noncompliance in a patient with end-stage renal disease.

Sleep disorders are relatively common in patients with end-stage renal disease, but the diagnosis may be difficult to establish because of the similarity of uremic symptoms to those of the sleep apnea syndrome. After excluding anatomic and metabolic disorders associated with excessive sleepiness and disordered breathing in sleep and after ensuring that the patient is receiving adequate dialysis, the sleep disorder should be diagnosed using polysomnography. Continuous positive pressure airway breathing is an effective treatment for hemodialysis patients with obstructive sleep apnea syndrome, but the use of this machinery requires patient compliance, as does the delivery of an adequate amount of dialysis. The difficulties adjusting to end-stage renal disease requiring dialysis can be multiplied by the coexistence of a sleep disorder that requires some ventilatory assistance at night; the case presented in this article characterizes precisely that circumstance.

Attitude to Health↗
PubMed1997

Psychophysiological insomnia: the behavioural model and a neurocognitive perspective.

A number of paradoxes are apparent in the assessment and treatment of psychophysiological insomnia and sleep state misperception. Three of these paradoxes exist as discrepancies between polysomnographic (PSG) measures and the subjective impressions regarding sleep quality and quantity. The remaining incongruity exists largely within the objective domain. In the case of subjective-objective discrepancies, patients with insomnia: (1) frequently identify themselves as having been awake when awakened from PSG defined sleep; (2) tend to overestimate sleep latency and underestimate total sleep time as compared with PSG measures; (3) appear to derive more benefit from pharmacotherapy that can be explained by objective gains. The remaining paradox pertains to the observation that hypnotic medications, by and large, do not normalize sleep architecture or produce a more 'sleep-like' EEG. In this paper, we review possible explanations for these various paradoxes, introduce a new perspective and suggest possible research avenues. The model introduced is based on the observation that beta and/or gamma activity (which have been found to be associated with cognitive processes) is enhanced in insomnia at or around sleep onset. We propose that this kind of high frequency EEG activity may interfere with the normal establishment of sleep onset-related mesograde amnesia. As a result, the patient with insomnia maintains a level of information and/or memory processing that blurs the phenomenological distinction between sleep and wakefulness and influences retrospective judgments about sleep initiation and duration.

Adaptation, Psychological↗
PubMed1997

A critical evaluation of the hypnotic efficacy of melatonin.

This paper reviews the available literature on the use of melatonin as a hypnotic in normal volunteers and in patients with noncircadian insomnias. Data are ordered in terms of studies of subject self-reports and polygraphic data and are seen in the context of generally accepted criteria for assessment of clinically used hypnotics. It is concluded that, at the present time, there is very little systematic evidence to suggest that melatonin has significant hypnotic efficacy in these populations.

Adult↗
PubMed1997

Efficacy of melatonin as a hypnotic agent.

The seemingly contradictory literature on the use of melatonin in insomnia is best understood by considering issues of time of administration (day or night), dose range (physiological or pharmacological), subject selection (normals or insomniacs), choice of dependent variable (self-report or electroencephalogram), and comprehensiveness of the reported variables (sleep onset or sleep maintenance). Available data on nighttime administration to normals and insomniacs are reviewed. It is concluded that there is not yet a convincing body of evidence, using generally accepted measures, that melatonin administration improves sleep in insomniacs with noncircadian sleep disturbance.

Humans↗
PubMed1997

Experiences of a sleep disorders center: 1700 patients later.

Sleep studies reveal many patients to have specific sleep abnormalities different from what might be suspected from the clinical history. For example, in our experience, patients who were later found to have central sleep apnea presented with chief complaints of excessive sleepiness or insomnia. In patients requesting evaluation for sleep apnea, screening studies that detect only sleep-disturbed breathing (ie, oximetry) may miss other diagnoses in one fourth of cases.

Adolescent↗
PubMed1996

Sleep induction by microinjection of pentobarbital into the medial preoptic area in rats.

In a previous study we have shown that microinjection of the benzodiazepine hypnotic triazolam into the medial preoptic area increases sleep in rats. In order to determine whether this effect is specific to benzodiazepines, or whether it occurs with hypnotic medications from other pharmacologic classes, we have microinjected pentobarbital (1 and 100 micrograms) and vehicle in random sequence into rats and performed two hour sleep studies in the daytime with the lights on. Both doses significantly decreased sleep latency and increased nonREM and total sleep. The amount of REM sleep, REM latency, and intermittent waking time were not significantly altered. These data are consistent with the hypothesis that the medial preoptic area may be involved in sleep induction by both benzodiazepine and barbiturate hypnotic medications.

Animals↗
PubMed1996

Are periodic leg movements associated with clinical sleep disturbance?

We examined 67 patients with periodic leg movement (PLM) disorder who were seen in a university-based sleep center. The most common reasons for coming to the sleep center were insomnia, sleepiness and a request for an evaluation for possible sleep apnea. There was a significant positive correlation between PLM arousal index and age but no association with gender. Approximately one-quarter of patients were under age 30. The multiple sleep latency test (MSLT) revealed borderline normal wakefulness in the group as a whole (sleep latency of 10.2 +/- 0.9 minutes), and there was no significant correlation between the PLM arousal index and either the MSLT mean sleep latency or a measure of subjective sleepiness. Similarly, the PLM arousal index did not differentiate those who entered with chief complaints of insomnia or sleepiness. There was no significant difference in the PLM arousal index in those who reported that they did or did not awaken refreshed in the morning. In summary, in this clinical population we found no significant association between the PLM arousal index and the subjective complaint of disturbed sleep, an objective measure of daytime sleepiness or a sense of awakening refreshed in the morning. Other interesting observations included the relatively high frequency of a PLM index > 5 in patients under 30 years old and a relatively high rate of past treatment for depression.

Adolescent↗
PubMed1996

Adverse reactions to sedative/hypnotics: three years' experience.

Reported adverse reactions to orally administered sedative/hypnotics were systematically recorded during a 3-year period in a 1,000-bed teaching hospital. Reported cases were reviewed by a multidisciplinary committee and then by a pharmacist, and judgments were made as to type, severity, and outcome of adverse reactions. Probability that the reaction was caused by the medication was recorded in terms of both a global judgment and a systematic scale. The frequency of adverse reactions was calculated as a percentage of total doses of each agent dispensed by the pharmacy during the same time period. The assessment of benzodiazepine sedative/hypnotics indicated that adverse reactions were rare, ranging from frequencies of 0.05% of doses administered (lorazepam) to none (chlorazepate). The median frequency of reported adverse reactions was 0.01%, or 1 in 10,000 doses. The vast majority of reactions could be viewed as extensions of the therapeutic effect, were considered mild, and were without sequelae. All adverse reactions occurred in patients over 55 years old except for four patients under age 50 who received lorazepam. There were no reported cases of violent behavior or global amnesia.

Accidental Falls↗
PubMed1996

The multiple sleep latency test: comparison of sleep onset criteria.

Determining sleep latency is one of the cornerstones of the interpretation of the multiple sleep latency test (MSLT). The purpose of this study was to compare various criteria used to determine sleep onset. We prospectively analyzed 100 consecutive MSLTs that were performed according to a standardized protocol. We scored each test using three separate sets of criteria for sleep onset: 1) one epoch of stage 1 sleep, 2) two consecutive epochs of stage 1 sleep, and 3) three consecutive epochs of stage 1 sleep. Each method yielded a mean sleep latency and a categorical classification of the record as normal if > 10 minutes, moderate if > or = 5 and < or = 10 minutes, and severe sleepiness if < 5 minutes. The ages of participants ranged from 4 to 78 years (mean 45.5). The averages of the mean sleep latencies across all three methods were: 6.2 minutes [standard deviation (SD) = 4.3] using one epoch, 7.2 minutes (SD = 4.7) using two epochs, and 7.5 minutes (SD = 4.9) using three epochs. Using the three categories of sleepiness, the implementation of the three-epoch criterion vs. the one-epoch criterion produced a change in category in 16 patients (16%). Five went from severe to moderate, 10 from moderate to normal, and 1 from severe to normal. As compared to using one epoch, using three produced an increase in mean sleep latency of at least 50% in 13 patients. The use of various criteria for sleep onset, especially criteria 1 and 3 above, produces differences in interpretation that are neither rare nor quantitatively negligible. Standardization of the methodology across centers would be desirable in clinical practice as well as for research protocols.

Adolescent↗
PubMed1996

The use of sedative/hypnotic medication and its correlation with falling down in the hospital.

The relationship between reports of falling down and the administration of sedative/hypnotics or other psychotropic drugs was examined during a 1-year period in a 1,000-bed teaching hospital. It was found that patients who fell were approximately 2.7 times as likely to have received a psychotropic drug compared to control subjects matched for age, gender, and medical service. Orally administered benzodiazepines that were significantly associated with falls included temazepam, alprazolam, diazepam, and lorazepam, but not triazolam, chlordiazepoxide, or chlorazepate. When viewed as the frequency of falls per dose dispensed by the pharmacy, the highest rates were with lorazepam (0.0012 falls/dose) and alprazolam (0.0010 falls/dose), whereas the lowest rate was for diazepam (0.00052 falls/dose). Falls with antidepressants were comparable to the higher rates with benzodiazepines; frequencies for nortriptyline and sertraline were 0.0021 and 0.0012 falls/dose, respectively. Patients receiving two or three psychotropic drugs concomitantly were 3.7 and 9.5 times, respectively, more likely to fall compared to control subjects. Patients under 21 years old who fell were also significantly more likely to have received a psychotropic medication compared to control subjects. Although these data are associational and do not necessarily imply causality, prudence indicates that the risk of falls be considered in making benefit/risk decisions about prescribing sedative/hypnotics.

Accidental Falls↗
PubMed1995

Effects of flurazepam and zolpidem on the perception of sleep in normal volunteers.

In previous studies we have reported that the benzodiazepine hypnotic triazolam and the nonbenzodiazepine zolpidem increase the likelihood that insomniacs will report having been asleep when awakened by an electronic tone of progressive intensity. It has not been known, however, whether this occurs with normal sleepers. In the present study we have administered placebo, flurazepam 30 mg and zolpidem 10 mg to 15 normal sleepers and awakened them with an electronic tone at five points across the night. In contrast to previous reports with insomniacs, both compounds made only modest improvements in sleep. When all time points were combined, subjects reported having been asleep in 40.3, 42.9 and 47.9% of the trials on placebo, flurazepam and zolpidem, respectively (ns). Subjects were accurate in their estimate of total time asleep, and this accuracy was not influenced by the drugs. Similarly, there were no effects on a variety of questions related to dreaming and other cognitive activity during sleep. These results suggest that the effects of these hypnotics, which have been described previously in insomniacs, are not found in normals. Further studies will be necessary to clarify whether such effects in insomniacs are related to the clinical efficacy of hypnotics.

Adult↗
PubMed1995

Effects of flurazepam and zolpidem on the perception of sleep in insomniacs.

We have shown previously that the benzodiazepine hypnotic triazolam alters the perception of being awake or asleep in insomniacs, making it more likely that they will report having been asleep when awakened by an electronic tone at various times of the night. In the present study, we examined the question as to whether this is also true for other benzodiazepines as well as for nonbenzodiazepine hypnotics. Ten insomniacs were given placebo, flurazepam 30 mg and zolpidem 10 mg and were awakened at five times during subsequent sleep in a random-sequence repeated-measures study. Across all five awakenings following placebo, insomniacs reported being asleep with a frequency of 30.9%. This rose to 40.4% (ns) and 54.7% (p < 0.03) on flurazepam and zolpidem, respectively. Subjects were also more likely to report having been dreaming during the awakening 5 minutes after "lights out" after receiving zolpidem. A number of polygraphic measures of sleep, including sleep latency, total sleep and sleep efficiency, improved significantly on both drugs, and there was similar improvement in some global measures of quality of sleep. Neither drug altered the subjective sense of duration of time. These findings suggest that drug-induced alterations in the perception of being awake or asleep are not unique to benzodiazepines, but occur with the nonbenzodiazepine zolpidem as well.

Adult↗
PubMed1995

Long-term follow-up of chronic insomnia.

In order to assess the long-term outcome of sleep disturbance, 28 well-characterized patients with psychophysiological insomnia or sleep state misperception were given structured interviews 40 months and 64 months after initial assessment. Most patients still reported sleep disturbance, albeit with some improvement. The number of nights per week of disturbed sleep decreased, subjective total sleep time increased, daytime sleepiness declined, there was an increase in feeling refreshed in the morning and there was a trend toward decreased global complaints of poor sleep. Subjective sleep latency was unchanged, and the only parameter that worsened was difficulty falling asleep. Only a minority of the patients (18%) were taking prescription hypnotics at follow-up, but these patients believed that they were of benefit. There was a significant rate of increase in the use of over-the-counter hypnotics at the time of the second follow-up, although there was a low rate of satisfaction associated with them.

Adult↗