Predisposition to and development and persistence of chronic insomnia: importance of psychobehavioral factors.
Explore the source record for details and available documents.
Behavior↗
Biomedical subjects
A Kales
Publications and source records attributed to A Kales.
Next-day memory impairment with triazolam use.
The prevalence, rate, and degree of memory impairment for next-day activities during a short, intermittent course of bedtime doses of triazolam, temazepam, and placebo were assessed in a double-blind parallel-group study. 5 of the 6 subjects in the triazolam group reported at least one episode of next-day memory impairment/amnesia, with a total of 12 episodes being reported for the 30 subject-drug nights (a rate of 40%). In the temazepam group there were no such episodes of memory impairment. Immediate and delayed recall were also tested and related to whether active drug or placebo had been taken the night before. Impairment of delayed recall was significantly and several times greater than that in the temazepam or placebo groups. Next-day memory impairment/amnesia after a bedtime dose of triazolam tended to increase with continued or intermittent drug use. Cognitive impairments associated with triazolam probably represent a spectrum of organic brain dysfunction, with memory impairment/amnesia and confusion being the commonest, and milder manifestations and hallucinations and delusions the more severe and less common, features.
Activities of Daily Living↗
Effects of lovastatin and pravastatin on sleep efficiency and sleep stages.
The effects on sleep of two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (40 mg lovastatin and 40 mg pravastatin) were evaluated in 12 normal subjects in a double-blind placebo-controlled sleep laboratory study. Subjects were randomly assigned to each of two parallel groups (lovastatin and pravastatin). Each parallel-group protocol consisted of 22 consecutive nights including 4 placebo-baseline nights, 2 weeks of drug administration, and 4 placebo-withdrawal nights. Lovastatin did not disturb sleep initially (nights 5 through 7) but, with continued administration (nights 16 through 18), it significantly and markedly increased wake time after sleep onset and stage 1 sleep compared with baseline. By contrast, pravastatin was not associated with sleep disturbance either initially or with continued use. Neither drug caused any sleep disturbance after withdrawal. Lovastatin's sleep disturbing effects with continued administration are attributed to its high degree of lipophilicity in contrast with the hydrophilicity of pravastatin.
Adult↗
Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines.
In three parallel groups, brief and intermittent administration and withdrawal of triazolam, 0.5 mg, temazepam, 30 mg, and placebo were assessed in a 12-night sleep laboratory study of 18 subjects with insomnia. With this intermittent schedule both drugs improved sleep, with about one-third reduction in total wake time; this reduction was significant for temazepam but not for triazolam. Even though the periods of drug administration were quite brief, withdrawal of triazolam consistently produced rebound insomnia, with increases in total wake time above baseline of 61% and 51%, respectively, for the first night of each withdrawal period. With temazepam this effect was more variable, with total wake time increased only with the second withdrawal period (39%). Thus these findings indicate that even under conditions of brief, intermittent use and withdrawal, triazolam and, to a lesser degree, temazepam produce rebound insomnia after abrupt withdrawal, thereby predisposing to drug-taking behavior and increasing the potential for drug dependence.
Adult↗
Buspirone: sedative or stimulant effect?
OBJECTIVE: The primary objectives of this study were to evaluate the effects of initial and continued administration of buspirone on sleep induction and maintenance and sleep stage parameters, to determine the presence or absence of any drug-induced side effects, and to ascertain the presence or absence of sleep disturbances following abrupt withdrawal of the drug. METHOD: Six insomniac subjects who had chronic complaints of difficulty falling asleep and/or staying asleep and who were in good physical health, were not suffering from any major mental disorders, and had not used any medication for at least the last month participated in a 16-night sleep laboratory protocol. The protocol consisted of 4 placebo-baseline nights, 7 nights on which buspirone, 10 mg at bedtime, was administered, and 5 placebo-withdrawal nights. RESULTS: Wake time after sleep onset increased moderately during the first 3 nights of drug administration (there was a marked and significant increase on the first night) and increased by lesser degrees with continued drug administration. Overall, reports of side effects were infrequent. Following drug termination, there was a delayed and mild increase in sleep difficulty above baseline. CONCLUSIONS: These data not only confirm that buspirone lacks sedative effects but also suggest that the drug may have stimulant properties. Further, these findings suggest that buspirone has limited usefulness in anxious patients with concomitant sleep difficulties.
Adult↗
Clonazepam: sleep laboratory study of efficacy and withdrawal.
Clonazepam 0.5 mg was evaluated in a sleep laboratory study of 6 insomniac patients. The 16-night protocol consisted of 4 placebo-baseline nights, 7 nights of drug administration and 5 placebo-withdrawal nights. Clonazepam produced a significant decrease in total wake time initially (nights 5-7), as well as with continued administration (nights 9-11). With later but not immediate withdrawal, significant rebound insomnia occurred, on the 3rd withdrawal night, both wake time after sleep onset and total wake time increased markedly, with the latter significantly increased. These findings are discussed in light of clonazepam's increasing use for panic disorder; specifically, due to its maintained efficacy, it has the advantage of avoiding interdose rebound anxiety which is frequently reported with use of alprazolam.
Adult↗
Benzodiazepine hypnotics and insomnia.
In summary, it is proposed that the more frequent or severe side effects associated with the newer triazolo-benzodiazepines are related to an interaction of several factors, including rapid elimination, high receptor-binding affinity, and unique chemical properties. Among benzodiazepine hypnotics, triazolam has a unique side effect profile for CNS adverse reactions in regard to type, frequency, and severity. All of the three factors mentioned contribute to this side effect profile: rapid elimination (the shortest half-life among benzodiazepine anxiolytics and hypnotics); high receptor-binding affinity (the highest among benzodiazepine anxiolytics and hypnotics); and unique chemical properties as a triazolo-benzodiazepine. Given these three factors, the drug's side effects can be understood as follows: Hyperexcitability states (daytime anxiety during drug administration and rebound insomnia following withdrawal) are related primarily to its rapid elimination and secondarily to the other two factors, whereas cognitive impairments (amnesia, confusion, and psychiatric symptoms) are related to the high binding affinity and unique chemical properties as well as to its rapid elimination. In contrast, benzodiazepines that are slowly eliminated and have only relatively moderate receptor-binding affinity (flurazepam) are unlikely to produce daytime anxiety and rebound insomnia and CNS adverse reactions such as cognitive impairment. The most common side effect, daytime sedation, is easily recognized and can be managed by dose reduction and/or intermittent use. This safety profile combined with the drug's high degree of efficacy both initially and with continued use provides a high benefit-risk ratio in using the drug in the adjunctive pharmacologic treatment of insomnia. Similarly, temazepam, which has relatively weak receptor-binding affinity produces very few CNS adverse reactions. Furthermore, temazepam (15 mg) is more efficacious than triazolam (0.25 mg). However, temazepam is not as effective as flurazepam, because it is slowly absorbed and therefore has limited efficacy for sleep induction. On the other hand, triazolam's safety profile of frequent and severe adverse reactions combined with the lack of efficacy for the current dose of 0.25 mg limits the drug's usefulness. In fact, the 0.25-mg dose has such a poor benefit-to-risk ratio that there is a real question as to whether the drug should remain on the market.(ABSTRACT TRUNCATED AT 400 WORDS)
Anti-Anxiety Agents↗
Quazepam: hypnotic efficacy and side effects.
Quazepam is a benzodiazepine hypnotic that can be useful in the adjunctive pharmacologic treatment of insomnia. It is slowly eliminated due to the long elimination half-lives of the parent compound and its two active metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam. This drug is recommended in doses of 15 mg for adults and 7.5 mg for geriatric patients. Sleep laboratory studies and clinical trials have shown that the 15 mg dose is quite efficacious for inducing and maintaining sleep not only with initial and short-term use but also with continued use. The 7.5 mg dose which has been studied less extensively has also been shown to be effective for inducing and maintaining sleep. There is considerable evidence of carryover effectiveness both during drug administration and after withdrawal. Thus, rebound phenomena are not observed during administration (early morning insomnia and daytime anxiety) and after withdrawal (rebound insomnia). Furthermore, certain behavioral side effects that have occurred with certain benzodiazepines (triazolam) have not been reported with quazepam. The only notable side effect seen with quazepam is a variable degree of daytime sedation, which can be minimized by intermittent use of the 15 mg dose when necessary and use of the 7.5 mg dose in the elderly. In comparison to triazolam and temazepam, quazepam is more effective with short-term use, and with continued use it maintains its efficacy in contrast to both of these drugs which show rapid development of tolerance. Most important, quazepam lacks the frequent and severe side effects increasingly reported with triazolam use or following its withdrawal.
Animals↗
Morphology of the uvula in obstructive sleep apnea.
Alterations in pharyngeal structure and function are considered fundamental in the pathogenesis of obstructive sleep apnea (OSA). However, little is known about morphologic features of the pharynx in patients with OSA. We therefore studied the tissue composition of the uvula (midsagittal section) in patients with OSA, using a quantitative, morphometric point-counting technique. Uvula tissue was obtained by uvulopalatopharyngoplasty (UPPP) in 33 patients (mean number of apneas per hour of sleep = 32.7 +/- 5.2) and by autopsy in 22 normal subjects not known to have OSA. All statistical comparisons were controlled for differences caused by age and body mass index. Patients with OSA had a significantly greater percentage of muscle in the uvula (18.1 +/- 1.9% versus 9.3 +/- 2.1%, p = 0.02) than did normal subjects. A significant difference in fat content was also found (9.5 +/- 1.4% in patients versus 4.0 +/- 1.0% in normal subjects, p less than 0.02). These differences between patients with OSA and control subjects could not be accounted for by anthropometric or sex differences. The percentage of uvula fat tissue was significantly related to the frequency of apneas and hypopneas in sleep (r = 0.43, p less than 0.01). Uvula morphology in 6 nonapneic snorers undergoing UPPP was similar to that of patients with OSA. We conclude that the uvula in patients with OSA contains more muscle and fat than the uvula in control subjects, possibly contributing to pharyngeal narrowing in OSA.
Female↗
An update on sleep disorders.
Sleep disorders are so common that approximately 38% of the general population complains about a current sleep problem and 52% complains about a current or past sleep problem. Psychiatric factors are prominent in virtually all sleep disorders, either as primary factors (insomnia and adult parasomnias) or as significant secondary consequences (sleep apnea and narcolepsy). The authors describe normal sleep; delineate the prevalence of sleep disorders, both those associated with psychiatric disturbance and those of organic etiology; and outline procedures for evaluation and treatment, which is multidimensional and comprises general measures, psychotherapy, and, when indicated, pharmacotherapy.
Adult↗
Effects of nadolol on blood pressure, sleep efficiency, and sleep stages.
The effects of nadolol (20 and 80 mg) on blood pressure and sleep parameters were assessed in six patients with mild hypertension. A 32-night experimental protocol in the sleep laboratory was instituted consisting of four placebo-baseline nights followed by 4 weeks of drug administration. Both doses of nadolol had a clear-cut and consistent lowering effect on blood pressure throughout the night and during the day, with a greater reduction noted with the 80 mg dose. In fact, blood pressure values were reduced to normotensive levels. Neither dose had a disrupting effect on sleep, whereas the 80 mg dose improved sleep efficiency and also had a rapid eye movement-enhancing effect. This absence of sleep-disrupting effects is attributed to nadolol's low level of lipophilicity and lack of intrinsic sympathomimetic activity. The clinical significance of the lack of sleep disruption and possible improvement of sleep with nadolol is discussed in light of the well-recognized sleep disturbances produced by other beta-blockers.
Adult↗
Nocturnal sleep and blood pressure in essential hypertension.
Blood pressure and sleep-wakefulness patterns were monitored in the sleep laboratory over four consecutive nights in six patients with mild hypertension and six age- and sex-matched controls. In both hypertensives and normals, blood pressure levels decreased during sleep compared with presleep levels by 16.6 and 8.4%, respectively; levels for hypertensives, however, remained significantly above those for the normals. The nocturnal drop in blood pressure for both groups appeared to be related primarily to the general state of sleep rather than to any specific sleep stage. Nocturnal patterns of sleep stages and sleep cycling were almost identical for the two groups. Nocturnal blood pressure fluctuation was correlated positively with the distribution of nocturnal wakefulness in hypertensives but not in normotensives. This suggests that with hypertension there is some diminution of the dampening effect of sleep itself upon blood pressure which normally carries over into periods of nocturnal wakefulness. This alteration in patients with mild hypertension may reflect a decrease in the sensitivity of the baroreceptor reflex or some other pathophysiological process.
Adult↗
Diazepam: effects on sleep and withdrawal phenomena.
Diazepam 10 mg was evaluated in a sleep laboratory study of six insomniac subjects. The protocol, which lasted for 18 consecutive nights, including four placebo-baseline, seven drug, and seven placebo-withdrawal nights, allowed for assessment of initial and short-term drug effects, side effects, and any withdrawal effects. With initial drug use, there was a significant improvement in sleep. Further, there was little evidence of tolerance developing at the end of the 1-week drug administration period. During drug administration there was a mild degree of daytime sedation reported. After abrupt termination of diazepam, there was a moderate degree of sleep difficulty on the sixth withdrawal night when total wake time was increased by 34% above baseline (not significant). On other nights, mild withdrawal changes were noted. These findings for the short-term administration and withdrawal of diazepam contrast with those for rapidly eliminated benzodiazepine drugs. The latter are characterized by a rapid development of tolerance and more frequent and intense withdrawal sleep disturbances.
Adult↗
Alprazolam: effects on sleep and withdrawal phenomena.
Alprazolam was evaluated in chronic insomniacs in a 1-mg bedtime dose. The 16-night sleep laboratory protocol included four placebo-baseline nights followed by seven nights of drug administration and five placebo-withdrawal nights. On the first three drug nights (nights 5 to 7), the drug was highly effective in inducing and maintaining sleep with this short-term use. By the end of the one week of administration (nights 9 to 11), however, the drug had lost about 40% of its efficacy. During drug use, one subject reported some difficulty in controlling expression of inappropriate emotions when interacting with others, which suggested the presence of disinhibition. On the third night following drug termination, there was a significant increase in sleep difficulty above baseline levels (rebound insomnia). This worsening was of comparable magnitude to the peak improvement of sleep with drug administration. Thus, the clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.
Adult↗
Inpatient multidimensional management of treatment-resistant insomnia.
Explore the source record for details and available documents.
Adolescent↗