Search

Background: Zolpidem is a non-benzodiazepine drug, approved by FDA for sleep induction. Zolpidem is thought to be a safer drug than benzodiazepines (BZD) because of no evidence of abuse or dependence potential, but several case reports of zolpidem abuse and dependence have been published along with a small number of cases demonstrating seizures after sudden zolpidem withdrawal. Case presentation: A 32-year-old unmarried woman suffering from major depressive disorder had been taking zolpidem for insomnia for more than 1 year. She began to take zolpidem alone without mixing other kinds of hypnotics, and 50 mg of zolpidem used to be initially effective in treating her insomnia. In some days the dose increased up to 100 mg per day. In the end, she had to discontinue zolpidem abruptly because she could not afford it anymore. After 2 days, she suddenly showed facial spasm, mouth opening, tonic-clonic seizure, and loss of consciousness for about 1-2 minutes. Post-ictal confusion with clouded consciousness, psycho-motor retardation, persisted in 1 day. EEG in wakefulness revealed intermittent, generalized, diffused alpha wave and diffused sharp waves, and suggested seizure waves in the patient. Conclusion: Our case suggested that the potential of zolpidem dependence and withdrawal seizure are also present in the Iranian population. The female-gender, high dosage and longterm use of zolpidem might be risk factors for the development of adverse effects. [ABSTRACT FROM AUTHOR]

Recent studies suggest that sleep differentially alters the activity of cortical neurons based on firing rates during preceding wake—increasing the firing rates of sparsely firing neurons and decreasing those of faster firing neurons. Because sparsely firing cortical neurons may play a specialized role in sensory processing, sleep could facilitate sensory function via selective actions on sparsely firing neurons. To test this hypothesis, we analyzed longitudinal electrophysiological recordings of primary visual cortex (V1) neurons across a novel visual experience which induces V1 plasticity (or a control experience which does not), and a period of subsequent ad lib sleep or partial sleep deprivation. We find that across a day of ad lib sleep, spontaneous and visually-evoked firing rates are selectively augmented in sparsely firing V1 neurons. These sparsely firing neurons are more highly visually responsive, and show greater orientation selectivity than their high firing rate neighbors. They also tend to be “soloists” instead of “choristers”—showing relatively weak coupling of firing to V1 population activity. These population-specific changes in firing rate are blocked by sleep disruption either early or late in the day, and appear to be brought about by increases in neuronal firing rates across bouts of rapid eye movement (REM) sleep. Following a patterned visual experience that induces orientation-selective response potentiation (OSRP) in V1, sparsely firing and weakly population-coupled neurons show the highest level of sleep-dependent response plasticity. Across a day of ad lib sleep, population coupling strength increases selectively for sparsely firing neurons—this effect is also disrupted by sleep deprivation. Together, these data suggest that sleep may optimize sensory function by augmenting the functional connectivity and firing rate of highly responsive and stimulus-selective cortical neurons, while simultaneously reducing noise in the network by decreasing the activity of less selective, faster-firing neurons. [ABSTRACT FROM AUTHOR]

Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures. [ABSTRACT FROM AUTHOR]

Depressed patients often complain of sleep disturbance. Routine antidepressive strategies sometimes fail to deal with this intractable issue. Indeed, the supplementation of sleep promoting antidepressants (eg, trazodone, mirtazapine, and agomelatine) is prevalent in clinical practice. However, the combination of different antidepressants may increase the affective lability. Herein, we document a patient with unipolar depression who was compliant with sertraline treatment and who dramatically switched to mania after adding trazodone as a sleeping aid. This case extended our understanding of the potential manic-switching risk when trazodone is used to promote sleep. [ABSTRACT FROM AUTHOR]

Interleukin-1β (IL-1β) and prostaglandin (PG) D 2 are endogenous sleep-promoting substances. Since it was reported that a highly selective cyclooxygenase-2 (COX-2) inhibitor, NS398, completely inhibited IL-1β-induced sleep in rats, IL-1β-induced sleep had been believed to be mediated by prostanoids, most probably PGD 2 . However, in the present study, pretreatment of rats with NS398 (3 mg/kg) did not suppress the 64.2% increased non-rapid eye movement (non-REM, NREM) sleep during infusion of IL-1β (10 ng) for 6 h in the nocturnal (active) period between 23:00 and 5:00 into the subarachnoid space of the PGD 2 -sensitive sleep-promoting zone of the basal forebrain. Meanwhile, IL-1β at doses of 1.7 and 5 μg/kg also significantly increased NREM sleep for 6 h after intraperitoneal injection at 20:00 (light-off time) by 76.8% and 121.1%, respectively, in wild-type (WT) mice, by 67.7% and 147.3%, respectively, in WT mice pretreated with NS398 (5 mg/kg) and by 108.9% and 121.6%, respectively, in PGD 2 receptor (DP 1 R) knockout mice. These results indicate that IL-1β-induced NREM sleep is independent of the PGD 2 /DP 1 R system and other COX-2-derived prostaglandins in rats and mice. [ABSTRACT FROM AUTHOR]

The article presents a commentary on the article "Melanopsin Regulates Both Sleep-Promoting and Arousal-Promoting Responses to Light," by V. Pilorz and colleagues. Information regarding the role of melanopsin in sleep and wake neural circuits, subset of photosenstive retinal ganglional cells (pRGCs), and the consistency of the arousing effects of blue light.

Aims This study was to investigate the sleep promoting effects of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP), by examining neuronal processes governing mRNA level alterations, as well as assessing neuromodulator concentrations, in a fruit fly model. Main methods Behavioral assays were applied to investigate subjective nighttime activity, sleep episodes, and total duration of subjective nighttime sleep of two amino acids and GABA/5-HTP mixture with caffeine treated flies. Also, real-time PCR and HPLC analysis were applied to analyze the signaling pathway. Key findings Subjective nighttime activity and sleep patterns of individual flies significantly decreased with 1% GABA treatment in conjunction with 0.1% 5-HTP treatment ( p < 0.001). Furthermore, GABA/5-HTP mixture resulted in significant differences between groups related to sleep patterns (40%, p < 0.017) and significantly induced subjective nighttime sleep in the awake model ( p < 0.003). These results related to transcript levels of the GABA B receptor (GABA B -R1) and serotonin receptor (5-HT1A), compared to the control group. In addition, GABA/5-HTP mixture significantly increased GABA levels 1 h and 12 h following treatment (2.1 fold and 1.2 fold higher than the control, respectively) and also increased 5-HTP levels (0 h: 1.01 μg/protein, 12 h: 3.45 μg/protein). Significance In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates subjective nighttime activity, sleep episodes, and total duration of subjective nighttime sleep to a greater extent than single administration of each amino acid, and that this modulation occurs via GABAergic and serotonergic signaling. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that blockade of the hypocretin receptor 1 may act as a useful pharmacotherapy for cocaine abuse. Here we investigated the extent to which various doses of a hypocretin receptor 1 antagonist, SB-334867, affect cocaine self-administration at varying doses of cocaine and across a range of effort requirements, and tested if these SB-334867 doses produce sedative effects. First, we trained animals to self-administer one of three doses of cocaine on a progressive ratio schedule, and then tested the effects of three doses of SB-334867. Responding for cocaine was then analyzed to segregate features of relatively high and low effort requirements across the progressive ratio session. In another set of experiments, we tested potential sleep-promoting effects of the same doses of SB-334867. Our data indicate that blockade of hypocretin receptor 1 preferentially reduces high effort responding for cocaine at levels that do not promote sedation. [ABSTRACT FROM AUTHOR]

Aims Previous studies showed enhanced attention and decreased inhibitory processes during early non-rapid eye movement sleep in primary insomnia patients, as measured by event-related potentials. The current study aims to examine information processing during sleep in non-insomniac individuals with high vulnerability ( HV) to stress-related sleep disturbances. Methods Twenty-seven non-insomniac individuals were recruited, 14 with low vulnerability and 13 with HV. After passing a screening interview and polysomnographic recording, subjects came to the sleep laboratory for 2 nights (a baseline night and a stress-inducing night) for event-related potentials recordings. Results The HV group demonstrated shorter P2 latency during the first 5 min of stage 2 sleep and higher P900 amplitudes under the stress condition during slow-wave sleep, which indicates an increased level of inhibitory processes. In addition, they had shorter N1 latencies during slow-wave sleep that could indicate an elevated level of attention processing during deep sleep. Conclusions Unlike patients with chronic insomnia, individuals with high sleep vulnerability to stress show a compensatory process that may prevent external stimulation from interfering with their sleep. This may be one of the factors preventing their acute sleep disturbances from becoming chronic problems. [ABSTRACT FROM AUTHOR]

Rationale: In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs. Objectives: The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep-wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated. Methods: The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep-wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABA-benzodiazepine (BZD) receptor antagonist, was injected 15 min before PRT and eckstolonol to reveal its hypnotic mechanism. Results: PRT administration (>250 mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (>12.5 mg/kg) and increased the amount of NREMS (50 mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil. Conclusions: We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABA receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative-hypnotics. [ABSTRACT FROM AUTHOR]

BACKGROUND Melatonin is synthesized in greater concentration at night, and it plays an important role in sleep regulation. This study aimed to evaluate the melatonin concentration in milk collected by milking during the night and evaluates its effect, with or without tryptophan supplementation, in the sleep quality of adult Wistar rats. RESULTS A difference ( P < 0.05) was observed between the milking times, where the milk obtained at 02:00 presented a higher melatonin concentration (39.43 pg mL−1) than that acquired at 15:00 (4.03 pg mL−1). A biological assay was also performed on 32 male adult Wistar rats distributed among four groups ( n = 8): those receiving an AIN-93M diet (control group) and three test groups [diets containing milk from milking at 02:00 (M2h), milking at 15:00 (M15h), and milking at 02:00 plus tryptophan supplementation ( M2hT)] for 28 days. It was observed that the control group did not differ ( P > 0.05) from the M15h group in terms of the levels of blood melatonin and urinary sulfatoxymelatonin, but differed from groups M2h and M2hT, whereas group M2hT presented higher blood melatonin and urinary sulfatoxymelatonin concentrations. CONCLUSION Combining the techniques of night milking with tryptophan supplementation resulted in production of milk that improves sleep quality in rats. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Summary: Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila’s sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c. [Copyright &y& Elsevier]

Summary: To advance the understanding of sleep regulation, we screened for sleep-promoting cells and identified neurons expressing neuropeptide Y-like short neuropeptide F (sNPF). Sleep induction by sNPF meets all relevant criteria. Rebound sleep following sleep deprivation is reduced by activation of sNPF neurons, and flies experience negative sleep rebound upon cessation of sNPF neuronal stimulation, indicating that sNPF provides an important signal to the sleep homeostat. Only a subset of sNPF-expressing neurons, which includes the small ventrolateral clock neurons, is sleep promoting. Their release of sNPF increases sleep consolidation in part by suppressing the activity of wake-promoting large ventrolateral clock neurons, and suppression of neuronal firing may be the general response to sNPF receptor activation. sNPF acutely increases sleep without altering feeding behavior, which it affects only on a much longer time scale. The profound effect of sNPF on sleep indicates that it is an important sleep-promoting molecule. [Copyright &y& Elsevier]

Abstract: Replacement of the dimethoxyphenyl moiety in the core skeleton of almorexant by appropriately substituted imidazoles afforded novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as potent dual orexin receptor antagonists. We describe in this Letter our efforts to further optimize the potency and brain penetration of these derivatives by fine-tuning of the pivotal phenethyl motif, and we comment on the sleep-promoting activity of selected compounds in a rat electroencephalographic (EEG) model. [Copyright &y& Elsevier]

Abstract: 5-Hydroxytryptamine (5-HT)2A antagonists are promising therapeutic agents for the treatment of sleep maintenance insomnias, but unlike hypnotics, they have limited effects on sleep initiation. This study evaluated the effects of several 5-HT2A antagonists (eplivanserin, volinanserin and AVE8488) alone and/or in combination with the short-acting hypnotic, zolpidem, on the rat sleep profile. A repeated-measures design was used in which rats were treated with eplivanserin (3 and 10 mg/kg, i.p. or p.o.), volinanserin (0.3–3 mg/kg, i.p.), AVE8488 (0.1–3 mg/kg, i.p.) and zolpidem (3 and 10 mg/kg, p.o.). In addition, animals received a combination of eplivanserin (3 mg/kg, p.o.) and zolpidem (3 mg/kg, p.o.). Electroencephalogram was analyzed for 6 h after administration. Eplivanserin did not modify wakefulness and non-rapid eye movement sleep (NREMS), while zolpidem (10 mg/kg po) induced a marked increase in NREMS duration. Volinanserin (1 and 3 mg/kg) and AVE8488 (0.3 mg/kg) similarly increased NREMS, while reducing wakefulness. Moreover, the 5-HT2A antagonists and, to a lesser extent, zolpidem, increased duration of NREMS episodes, while decreasing their frequency. When eplivanserin was co-administered with zolpidem, a synergistic effect was observed as the combination produced an increase in NREMS time and bouts duration. These findings confirm further that 5-HT2A antagonists promote the maintenance of sleep, and suggest that combining a 5-HT2A antagonist with a short-acting hypnotic may be a useful strategy for the treatment of insomnia. [Copyright &y& Elsevier]

In patients with depression, characteristic changes of sleep electroencephalogram and nocturnal hormone secretion occur including rapid eye movement (REM) sleep disinhibition, reduced non-REM sleep and impaired sleep continuity. Neuropeptides are common regulators of the sleep electroencephalogram (EEG) and nocturnal hormone secretion and changes in their activity appear to contribute to the aberrances of sleep in affective disorders. A reciprocal interaction of the sleep-promoting growth hormone-releasing hormone (GHRH) and corticotrophin- releasing hormone (CRH), which promotes wakefulness and REM sleep, plays a key role in sleep regulation, at least in male subjects. Also galanin and ghrelin promote sleep in men. Neuropeptide Y is involved in the timing of sleep onset. The effects of peptides of sleep are influenced by the time of administration, age, gender and depression. In healthy subjects and in remitted depressed patients motoric memory learning is consolidated during sleep. This effect is absent in depressed patients who are at least 30 years old, and is probably related to elevated glucocorticoid levels. [ABSTRACT FROM AUTHOR]

The article contains a historical note on the concept of sleep hygiene, developed in 1977 by Peter Hauri, who developed a set of sleep-promoting rules, considered the fundament for sleep-hygiene techniques. Somnologists, unanimously ascribed to Hauri the fatherhood of the lucky term, while numerous books included at least a section on sleep hygiene. 'Inadequate sleep hygiene' was included as a nosological entity in the International Classification of Sleep Disorders. This article intends to demonstrate that the concept of sleep hygiene was developed many years before, thanks to the pioneering work of Paolo Mantegazza, a scientist and a professor in the Medical School of the University of Pavia, Italy. After presenting briefly the history of the University of Pavia and illustrating the profile of Paolo Mantegazza, the article presents the original book published by Mantegazza in 1864 (second edition in 1865). The authors report extensive citations of Mantegazza's original book dealing with sleep hygiene. Mantegazza's indications, compared with Hauri's rules show important similarities. The authors support the view that the fatherhood of sleep hygiene should be acknowledged to Mantegazza and antedated to 1864. Hauri keeps the merit of giving more solid scientific roots to the concept of sleep hygiene and of inserting it in the frame of modern sleep medicine. [ABSTRACT FROM AUTHOR]

Morphine is the most efficacious and widely prescribed treatment for pain. However, it decreases the total amount of deep sleep and rapid eye movement sleep in humans. Acute morphine administration at low doses causes wakefulness in animal models. To clarify the mechanism by which morphine affects sleep-wake behavior, we investigated the effects of morphine on the sleep-promoting neurons of the ventrolateral preoptic area (VLPO), a putative sleep-active nucleus, using in vitro brain slices by the patch-clamp technique. We also examined the effects of morphine on sleep-wake profiles after administration of opioid receptor antagonist to the VLPO using EEG and electromyogram recordings in freely moving rats. The results showed that morphine inhibited the firing rate of sleep-promoting neurons and hyperpolarized their membrane potentials without affecting interneurons in the VLPO. Morphine-induced hyperpolarization of membrane potentials could be reversed by, D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a mu receptor antagonist, in the presence of tetrodotoxin. However, after the mu receptors were blocked by CTOP, morphine still suppressed the firing of the sleep-promoting neurons. This effect was antagonized by nor-BIN, a kappa receptor antagonist. Activation of kappa receptor by U50488H inhibited the firing of the sleep-promoting neurons. These results indicate that morphine could inhibit the activity of sleep-promoting neurons in the VLPO through mu and kappa receptors. EEG recordings revealed that morphine injected subcutaneously induced arousal in a dose-dependent manner. CTOP microinjected into VLPO antagonized the arousal effects of morphine, but nor-BIN did not. However, CTOP alone was not associated with any changes in the physiological sleep-wake cycle. Taken together, these findings clearly indicate that morphine inhibits sleep-promoting neurons in the VLPO by affecting mu receptors and so induces wakefulness in rats. [ABSTRACT FROM AUTHOR]

Neuroendocrine mechanisms are major determinants of the normal 24-h blood pressure (BP) pattern. At the central level, integration of the major driving factors of this temporal variability is mediated by circadian rhythms of monoaminergic systems in conjunction with those of the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone, plus endothelial systems and specific vasoactive peptides. Humoral secretions are typically episodic, coupled either to sleep and/or the circadian endogenous (suprachiasmatic nucleus) central pacemaker clock, but exhibiting also weekly, monthly, seasonal, and annual periodicities. Sleep induction and arousal are influenced also by many hormones and chemical substances that exhibit 24-h variation, e.g., arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin, insulin, steroids, serotonin, corticotropin-releasing factor, adrenocorticotropic hormone, thyrotropin-releasing hormone, endogenous opioids, and prostaglandin E2, all with established effects on the cardiovascular system. As a consequence, physical, mental, and pathologic stimuli that activate or inhibit neuroendocrine effectors of biological rhythmicity may also interfere with, or modify, the temporal BP structure. Moreover, immediate adjustment to exogenous components/environment demands by BP rhythms is modulated by the circadian-time-dependent responsiveness of biological oscillators and their neuroendocrine effectors. This knowledge contributes to a better understanding of the pathophysiology of abnormalities of the 24-h BP pattern and level and their correction through circadian rhythm-based chronotherapeutic strategies. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

Summary: Background: Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Results: Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Conclusions: Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. [Copyright &y& Elsevier]

The critical closing pressure (Pcrit) is the airway pressure at which the airway collapses and reflects the anatomical contribution to the genesis of obstructive sleep apnea. Pcrit is usually determined during non-rapid eye movement sleep at night, but has been determined under midazolam sedation during the day in the absence of sleep stage monitoring. Indeed, little is known about the effects of midazolam on sleep architecture. Moreover, deeper sedation with midazolam can decrease upper airway muscle activity and increase collapsibility compared with natural sleep. Pcrit under sedation has not been systematically compared with the usual method performed during natural sleep. Therefore, this study aimed to test the hypothesis that Pcrit following low doses of midazolam during the day would be comparable to Pcrit measured during natural sleep in the same patient. Fifteen men (age 54 ± 10 yr, body mass index 30 ± 4 kg/m²) with obstructive sleep apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index 38 ± 22 events/h, range: 8-66 events/h), and Pcrit was determined during natural sleep and following midazolam. Sleep induction was obtained with low doses of midazolam (2.4 mg, range 2.0-4.4 mg), and sleep architecture was comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (-0.82 ± -3.44 and -0.97 ± 3.21 cmH2O, P = 0.663) and closely associated (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.78-0.97, P < 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep apnea severity, indicating that both Pcrit measures provided meaningful physiological information. Pcrit determined during the day with sleep induction is similar to natural overnight sleep and is a valid alternative approach in which to determine Pcrit. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate whether the outcome of treatment with trazodone CR in primary insomnia differs between patients with and without subthreshold depression. Methods: 14 patients (9 females, mean age 57.3±13.3) with primary insomnia and increased Beck Depression Inventory (BDI) scores (>10) and 15 sex- and age-matched patients with primary insomnia and low BDI scores (≤10) were treated with trazodone CR 25–150mg/d for 3months and followed for 1month after discontinuation of the medication. The Athens Insomnia Scale (AIS), Sheehan Disability Scale (SDS), and Clinical Global Impression scale (CGI) were completed at baseline, after each month of treatment and after the first week of run-out phase. Additional assessment tools comprised sleep diaries, the Leeds Sleep Evaluation Questionnaire (LSEQ) and actigraphic recordings. Results: Subjective sleep time increased by 61.5±72.3min in the group with low BDI and 60.0±59.4min in the group with increased BDI at the end of the treatment phase. The significant improvements were also observed in the AIS, CGI, LSEQ and SDS. During the run-out phase the improvement was sustained in patients with low BDI, while AIS scores, sleep latency and total sleep time deteriorated in patients with increased BDI. Conclusions: Patients with subthreshold depression, even if the depressive symptoms do not fulfill the time criteria for depressive episode, show marked worsening of insomnia after discontinuation of sleep promoting medication. [Copyright &y& Elsevier]

What puts us to sleep? This question has bothered the mankind for thousands of years, but we still have no definite answer. After abandoning philosophical and religious explanations, science has adopted this question and started to examine it with experimental methods. Two early pioneers in this field, Dr. Ishimori from Japan and Drs. Pieron and Legendre from France developed the concept of hypnotoxin - a factor that accumulates during waking and puts animals and humans to sleep. They were able to show that, indeed, during deprivation of sleep, something accumulates in body - something that can be removed and will induce sleep in another individual. Later research has identified many substances that affect sleep. One of them is adenosine, which fulfils the criteria of a physiologic sleep factor. [ABSTRACT FROM AUTHOR]

Adenosine is a candidate sleep substance. It can be both a distress signal of importance in pathology and a physiological regulator. Key factors in determining which of these possibilities pertain are: (i) the number of receptors expressed, and (ii) the mechanisms that establish extracellular adenosine levels. The roles of adenosine are studied by means of antagonists and/or animals (mostly mice) with targeted deletions of receptors or enzymes involved in adenosine metabolism. Whereas adaptive changes in the genetically modified mice can occur for the physiologically important effects, such adaptive changes are less likely to occur in situations where adenosine acts as a distress signal. The relevance to sleep will be covered only in general terms in this review and will be covered in other contributions to this volume. [ABSTRACT FROM AUTHOR]

Prostaglandin D (PGD) is the most potent endogenous sleep-promoting substance thus far reported. We have extensively studied its action mechanism at the molecular level. PGD is produced by lipocalin-type PGD synthase, which is dominantly localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain; and it is secreted into the cerebrospinal fluid and stimulates DP receptors localized in the arachnoid membrane of the ventral surface from the basal forebrain to the hypothalamus to increase the extracellular concentration of adenosine as a paracrine sleep-promoting molecule. Adenosine diffuses into the brain parenchyma, suppresses cholinergic arousal neurons in the basal forebrain via adenosine A receptors, activates sleep-active neurons in the ventrolateral preoptic area via adenosine A receptors, and concomitantly suppresses the histaminergic arousal center in the tuberomammillary nucleus through GABAergic and galaninergic inhibitory projections. Administration of an inhibitor of lipocalin-type PGD synthase (SeCl), an antagonist of DP receptors (ONO-4127Na) or an antagonist of adenosine A receptors (caffeine) results in sleep inhibition in rats and mice, indicating that the PGD-adenosine system is crucial for the maintenance of physiological sleep. [ABSTRACT FROM AUTHOR]

Background: Sleep is known to improve the yield of EEG recording in children but is often difficult to obtain. In order to evaluate the efficacy and to test the practability of oral melatonin in obtaining sleep for EEG recording, we studied its use in 70 children. Results: Sleep was obtained in 56 children (80%) with a mean sleep latency onset of 25±7.9mm (15-45) after melatonin administration, and a mean sleep duration of 17.1 ±8.6mm (5-55). 28 children (50%) woke up spontaneously after 13.2±7.9mm (5-40). Among 18 children with severe behaviour problems that made interpretable EEG recording in the awake state impossible, sleep was obtained in 13 (72%) children. The rare symtoms reported (4%) were not reliably related to the use of melatonin. Conclusion: The study shows a very good efficacy in sleep induction for EEG recording, even in children with severe behaviour problems. Sleep duration was, however, short with a high proportion of spontaneous arousals but in all patients it was sufficient for an initial diagnosis or control of the evolution of epilepsy. [ABSTRACT FROM AUTHOR]

Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake–sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake–sleep transitions. [Copyright &y& Elsevier]

Abstract: The hypocretin (orexin) neurons in the lateral hypothalamus play a crucial role in the promotion of arousal. Adenosine, an endogenous sleep-promoting factor, modulates both neuronal excitatory and synaptic transmission in the CNS. In this study, the involvement of endogenous adenosine in the regulation of excitatory glutamatergic synaptic transmission to hypocretin neurons was investigated in the hypothalamic slices from transgenic mice by using different frequencies of stimulation. A train of low-frequency stimulation (0.033, 1 Hz) had no effect on the amplitude of evoked excitatory postsynaptic currents (evEPSCs) in hypocretin neurons. Blockade of adenosine A1 receptors with selective A1 receptor antagonist 8-cyclopentyltheophylline (CPT), the amplitude of evEPSCs did not change during 0.033 and 1 Hz stimuli. When the frequency of stimulation was increased upto 2 Hz, a time-dependent depression of amplitude was recorded in hypocretin neurons. Administration of CPT caused no significant change in depressed synaptic response induced by 2 Hz stimulus. While depression induced by 10 and 100 Hz stimuli was partially inhibited by the CPT but not by the selective A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine. Further findings have demonstrated that high-frequency stimulation could induce long-term potentiation (LTP) of glutamatergic synaptic transmission to hypocretin neurons in acute hypothalamic slices. The experiments with CPT suggested that A1 receptor antagonist could facilitate the induction of LTP, indicating that endogenous adenosine, acting through A1 receptors, may suppress the induction of LTP of excitatory synaptic transmission to hypocretin neurons. These results suggest that in the hypothalamus, endogenous adenosine will be released into extracellular space in an activity-dependent manner inhibiting both basal excitatory synaptic transmission and LTP in hypocretin neurons via A1 receptors. Our data provide further support for the notion that hypocretin neurons in the lateral hypothalamus may be another important target involved in the endogenous adenosine modulating the sleep and wakefulness cycle in the mammalian CNS. [Copyright &y& Elsevier]

Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky. [ABSTRACT FROM AUTHOR]

Adenosine, a purine nucleoside has been described as a 'retaliatory metabolite' by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT) and Wolff Parkinson White (WPW) syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions. [ABSTRACT FROM AUTHOR]

Pineal melatonin is synthesized and secreted in close association with the light/dark cycle. The temporal relationship between the nocturnal rise in melatonin secretion and the “opening of the sleep gate” (i.e., the increase in sleep propensity at the beginning of the night), coupled with the sleep-promoting effects of exogenous melatonin, suggest that melatonin is involved in the regulation of sleep. The sleep-promoting and sleep/wake rhythm regulating effects of melatonin are attributed to its action on MT1 and MT2 melatonin receptors present in the suprachiasmatic nucleus (SCN) of the hypothalamus. Animal experiments carried out in rats, cats, and monkeys have revealed that melatonin has the ability to reduce sleep onset time and increase sleep duration. However, clinical studies reveal inconsistent findings, with some of them reporting beneficial effects of melatonin on sleep, whereas in others only marginal effects are documented. Recently a prolonged-release 2-mg melatonin preparation (CircadinTM) was approved by the European Medicines Agency as a monotherapy for the short-term treatment of primary insomnia in patients who are aged 55 or above. Several melatonin derivatives have been shown to increase nonrapid eye movement (NREM) in rats and are of potential pharmacological importance. So far only one of these melatonin derivatives, ramelteon, has received approval from the U.S. Food and Drug Administration to be used as a sleep promoter. Ramelteon is a novel MT1 and MT2 melatonergic agonist that has specific effects on melatonin receptors in the SCN and is effective in promoting sleep in experimental animals such as cats and monkeys. In clinical trials, ramelteon reduced sleep onset latency and promoted sleep in patients with chronic insomnia, including an older adult population. Both melatonin and ramelteon promote sleep by regulating the sleep/wake rhythm through their actions on melatonin receptors in the SCN, a unique mechanism of action not shared by any other hypnotics. Moreover, unlike benzodiazepines, ramelteon causes neither withdrawal effects nor dependence. Agomelatine, another novel melatonergic antidepressant in its final phase of approval for clinical use, has been shown to improve sleep in depressed patients and to have an antidepressant efficacy that is partially attributed to its effects on sleep-regulating mechanisms. [ABSTRACT FROM AUTHOR]

Carbachol, a cholinergic agonist, and GABAA receptor antagonists injected into the pontine dorsomedial reticular formation can trigger rapid eye movement (REM) sleep-like state. Data suggest that GABAergic and cholinergic effects interact to produce this effect but the sites where this occurs have not been delineated. In urethane-anesthetized rats, in which carbachol effectively elicits REM sleep-like episodes (REMSLE), we tested the ability of 10 nL microinjections of carbachol (10 mm) and bicuculline (0.5 or 2 mm) to elicit REMSLE at 47 sites located within the dorsal pontine reticular formation at the levels -8.00 to -10.80 from bregma (B) (Paxinos and Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego, 1997). At rostral levels, most carbachol and some bicuculline injections elicited REMSLE with latencies that gradually decreased from 242 to 12 s for carbachol and from 908 to 38 s for bicuculline for more caudal injection sites. As the latencies decreased, the durations of bicuculline-elicited REMSLE increased from 104 s to over 38 min, and the effect was dose dependent, whereas the duration of carbachol-elicited REMSLE changed little (104–354 s). Plots of REMSLE latency versus the antero-posterior coordinates revealed that both drugs were maximally effective near B-8.80. At levels caudal to B-8.80, carbachol was effective at few sites, whereas bicuculline-elicited REMSLE to at least B-9.30 level. Thus, the bicuculline-sensitive sites extended further caudally than those for carbachol and antagonism of GABAA receptors both triggered REMSLE and controlled their duration, whereas carbachol effects on REMSLE duration were small or limited by its concurrent REMSLE-opposing actions. [ABSTRACT FROM AUTHOR]

The article presents a study by Shantha M. W. Rajaratnam of Harvard Medical School and colleagues. It discusses a study of the melatonin agonist tasimelteon. It investigated the potential of tasimelteon use in transient insomnia caused by shifts in the sleep-wake cycle, a problem for travelers crossing time zones and night shift workers. It compared a group given tasimelteon to a placebo group.The tasimelteon group showed greater sleep efficiency and less sleep latency than the placebo group. Shortcomings of the study included small sample sizes and inability to detect changes in mood and performance. The study suggests tasimelteon has potential use in circadian rhythm transient insomnia.

Breast-milk contains a potent mixture of diverse components, such as the non-protein nitrogen fraction which includes nucleotides, whose variation in levels is evident throughout lactation. In addition, these substances play an important role in sleep homeostasis. In the present study, human milk samples were analyzed using a capillary electrophoresis system. The rhythmicity of each nucleotide was studied by cosinor analysis. It was found that the nucleotides 5′AMP, 5′GMP, 5′CMP, and 5′IMP have significant (P < 0.05) circadian rhythms, the acrophases of the first two being during the night, and of the latter two during the day. While 5′UMP did not show a clear circadian rhythm, there was an increase in its levels at night. In conclusion, the rise in nocturnal levels of 5′AMP, 5′GMP, and 5′UMP could be involved in inducing the 'hypnotic' action of breast-milk at night in the infant. [ABSTRACT FROM AUTHOR]

Abstract: γ-Hydroxybutyrate (GHB) is a euphoric, prosocial and sleep inducing drug that binds with high affinity to its own GHB receptor site and also more weakly to GABAB receptors. GHB is efficacious in the treatment of narcolepsy and alcoholism, but heavy use can lead to dependence and withdrawal. Many effects of GHB (sedation, hypothermia, catalepsy) are mimicked by GABAB receptor agonists (e.g. baclofen). However other effects (euphoric and prosocial effects and a therapeutic effect in narcolepsy) are not. The present study used Fos immunohistochemistry to assess the neural activation produced in rat brain by medium to high doses of GHB (250, 500 and 1000 mg/kg) and a high dose of baclofen (10 mg/kg) that produced similar sedation to 500 mg/kg GHB. Results showed many common regions of activation with these two drugs including the supraoptic, paraventricular, median preoptic and ventral premammillary nuclei of the hypothalamus, the central nucleus of the amygdala, Edinger-Westphal nucleus, lateral parabrachial nucleus, locus coeruleus, and nucleus of the solitary tract. GHB (500 mg/kg), but not baclofen (10 mg/kg), induced significant Fos expression in the median raphe nucleus and lateral habenula, while a higher dose of GHB (1000 mg/kg) induced additional Fos expression in the islands of Calleja, dentate gyrus (polymorphic layer) and arcuate nucleus, and in various regions implicated in rapid and non-rapid eye movement sleep (laterodorsal tegmental nucleus, tuberomammillary nucleus and the ventrolateral and anterodorsal preoptic nuclei). Surprisingly, Fos immunoreactivity was not observed with either GHB or baclofen in reward-relevant regions such as the nucleus accumbens, striatum and ventral tegmental area. Overall these results indicate a distinctive signature of brain activation with GHB that may be only partly due to GABAB receptor effects. This confirms a unique neuropharmacological profile for GHB and indicates key neural substrates that may underlie its characteristic influence on sleep, body temperature, sociability and endocrine function. [Copyright &y& Elsevier]

The article evaluates the pilot study which was conducted to determine the occurrence and characteristics of sleep disruption reported by adults during hospitalization. Findings indicate the need for the clinical nurse to assess patient sleep patterns during hospitalization and the evaluate the need for sleep promotion strategies. Current stress and illness were also found to contribute to sleep loss.

Concerns regarding a child's sleep, identified by a caregiver or by the health care practitioner, are commonly raised but often left unexplored. Families in geographically isolated areas, with limited access to specialty services such as pediatric sleep medicine, are at increased risk for unmet treatment needs. Telehealth is a potential vehicle for delivery of these specialty services and overcoming barriers in diagnosing and treating sleep disorders in children by improving access and enhancing support for the families in their communities. This article describes the initiation of a pilot program in the delivery of multidisciplinary pediatric sleep medicine services via telehealth in Alberta, Canada. [ABSTRACT FROM AUTHOR]

Abstract: Cortical surface evoked potentials (SEPs) are larger during sleep and characterize a sleep-like state in cortical columns. Since tumor necrosis factor alpha (TNF) may be involved in sleep regulation and is produced as a consequence of waking activity, we tested the hypothesis that direct application of TNF to the cortex will induce a sleep-like state within cortical columns and enhance SEP amplitudes. We found that microinjection of TNF onto the surface of the rat somatosensory cortex enhanced whisker stimulation-induced SEP amplitude relative to a control heat-inactivated TNF microinjection. We also determined if whisker stimulation enhanced endogenous TNF expression. TNF immunoreactivity (IR) was visualized after 2 h of deflection of a single whisker on each side. The number of TNF-IR cells increased in layers II–IV of the activated somatosensory barrel column. In two separate studies, unilateral deflection of multiple whiskers for 2 h increased the number of TNF-IR cells in layers II–V in columns that also exhibited enhanced cellular ongogene (Fos-IR). TNF-IR also colocalized with NeuN-IR suggesting that TNF expression was in neurons. Collectively these data are consistent with the hypotheses that TNF is produced in response to neural activity and in turn enhances the probability of a local sleep-like state as determined by increases in SEP amplitudes. [Copyright &y& Elsevier]

Insomnia, which is severe enough to warrant treatment, occurs in ∼10% of the general population. It is associated with a range of adverse consequences for human health, economic productivity and quality of life. In animal and human studies, administration of melatonin has been reported to promote sleep, although there has been controversy regarding its effectiveness. The present study used a chronically implanted radiotelemetry transmitter to record electroencephalogram (EEG) and electromyogram (EMG) to enable discrimination of wake (W), nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in un-restrained rats. The acute action of melatonin and ramelteon, a melatonin agonist recently approved for long-term treatment of insomnia in the USA, was examined. Radioligand binding assays on recombinant human MT1/MT2 receptors showed that both the melatonin and ramelteon were both high affinity, nonsubtype selective ligands. Both compounds acted as potent full agonists on a cellular model of melatonin action, the pigment aggregation response in Xenopus laevis melanophores. Both melatonin and ramelteon (10 mg/kg, i/p), administered close to the mid-point of the dark phase of the L:D cycle, significantly reduced NREM sleep latency (time from injection to the appearance of NREM sleep). Both the drugs also produced a short-lasting increase in NREM sleep duration, but the NREM power spectrum was unaltered. Neither drug altered REM latency, REM sleep duration nor power spectrum during REM sleep. In conclusion, ramelteon administration, like melatonin, exerted an acute, short-lasting sleep-promoting effect in the rat, the model most commonly used to evaluate the activity of novel hypnotic drugs. [ABSTRACT FROM AUTHOR]

The ability of biological sex and sex-driven characteristics to alter sleep states may contribute to gender disparities in sleep disorders. Sex influences sleep-wake amount, the daily timing of the sleep-wake cycle, and the ability to restore sleep after extended wakefulness. Several lines of evidence suggest that in mammals, reproductive hormones are responsible for the effects of sex on sleep and may have organizational and activational influences on sleep regulatory mechanisms. In humans, exogenously administered estrogens and progestins generally enhance sleep amount and continuity, whereas androgens appear to have a positive impact on rapid eye movement (REM) sleep but disrupt sleep consolidation. In rodent studies, however, female reproductive hormones appear to enhance wakefulness, and male gonadal hormones reinforce sleep. Rodent studies have also revealed that neonatal exposure to reproductive hormones organizes adult sleep-wake architecture. This paper reviews how sex and reproductive hormones interact with circadian and homeostatic sleep regulatory mechanisms in humans and animal models. We examine the organizational and activational nature of these interactions and also review how these interactions change with advancing age. Finally, we discuss the potential for genetic sex to influence sleep states. It is our hope that a better understanding of the mechanisms through which sex influences sleep-wake states will lead to improvements in the design of studies that examine gender disparities in sleep-wake disorders. [ABSTRACT FROM AUTHOR]

The purpose of our analysis was to determine if older adults show sleep inertia effects on performance at scheduled wake time, and whether these effects depend on circadian phase or sleep stage at awakening. Using the Digit Symbol Substitution Test, effects of sleep inertia on performance were assessed over the first 30 mm after wake time on baseline days and when sleep was scheduled at different circadian phases. Mixed model analyses revealed that performance improved as time awake increased; that beginning levels of performance were poorest when wake time was scheduled to occur during the biological night; and that effects of sleep inertia on performance during the biological night were greater when awaking from non-REM (NREM) sleep than from REM sleep. Based on our current understanding of sleep inertia effects in young subjects, and previous reports that older subjects awaken at an earlier circadian phase and are more likely to have their final awakening from NREM sleep than younger adults, our findings suggest older adults may be more vulnerable to sleep inertia effects than young adults. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the possibility of performing nose-to-brain delivery of TS-002, which is an analog compound of prostaglandin D2 (PGD2) and thus would be a natural sleep inducer. The absolute bioavailability (BA) and sleep-inducing effect (SIE) following intranasal (IN) administration of TS-002 dry powder to cynomolgus monkeys were evaluated in comparison with intravenous (IV) administration. The SIE was evaluated as the accumulated time of sleeping-posture for 3 h. The brain distribution of TS-002 following IN administration of the dry powder was examined in rats. The absolute bioavailability (BA) in monkeys following IN administration of the dry powder (0.4-1.2 mg/body) was comparatively high (43.4-78.0%). The SIE following IN administration (0.05-0.4 mg/body) showed dose-dependency and its effect at 0.4 mg/body was twice as strong as that for IV administration (P < 0.05). The brain concentrations in rats following IN administration (0.1 mg/kg) were obviously higher than that for IV administration at the same dose. The highest content was observed in the olfactory bulb. These results demonstrated that TS-002 was directly transported from the olfactory region to brain, thereby showing that it may be possible to develop a novel sleep-inducing drug based on nose-to-brain delivery. [ABSTRACT FROM AUTHOR]

AIMS AND OBJECTIVES: The objectives of this systematic review were to determine the most effective tools for the assessment and diagnosis of sleep problems, as well as identify the most effective strategies for the promotion of sleep within this population. BACKGROUND: Experiencing reduced sleep quality is often associated with normal ageing, however this may be exacerbated for residents of aged care facilities. External factors such as noise, light and night-time nursing may impact negatively upon sleeping patterns. METHODS: Eleven electronic databases and the reference lists and bibliographies of included studies were searched. Papers were grouped according to type of intervention or assessment tool and presented in a narrative summary. CONCLUSIONS: The review identified many interventions to promote sleep. Multidisciplinary strategies such as combining a reduction in environmental noise, reduction of night-time nursing care and promotion of daytime activity, are likely to be most effective for promoting sleep in the population of interest. The use of sedating medications is cautioned, as their long-term efficacy in promoting sleep is questionable. Wrist actigraphy was found to be the most accurate objective sleep assessment tool. RELEVANCE TO CLINICAL PRACTICE: Lack of sleep, disturbed sleep and the overuse of medications especially sedations reduce the quality of life for older people. Effective, safe sleep interventions should be promoted and practised by nurses. [ABSTRACT FROM AUTHOR]

Insufficient daytime sleep may result in reduction of effectiveness and safety during overnight military missions. The usefulness of temazepam and zaleplon to optimize afternoon sleep and their effects on performance and alertness during a subsequent night shift were studied. Method: In a randomized double-blind within-subjects design, 11 subjects took 20 mg of temazepam, 10 mg of zaleplon, or placebo before a 5:30-10:00 p.m. sleep period. Sleep length and quality were measured. Subjects were kept awake throughout the night while alertness, cognitive performance, and muscle power were repeatedly measured. Results: Temazepam provided significantly longer and qualitatively better sleep than zaleplon or placebo. During the night, sleepiness increased and muscle power was impaired in all conditions. Better sleep was correlated with less sleepiness during the night. Conclusion: Temazepam is useful to optimize a 4.5-hour afternoon sleep before overnight missions. Irrespective of hypnotic treatment, sleepiness and fatigue increased during the night shift. [ABSTRACT FROM AUTHOR]

This paper reviews the use of sleep-promoting medications in nursing home residents with reference to risks versus benefits. Up to two-thirds of elderly people living in institutions experience sleep disturbance. The aetiology of sleep disturbance includes poor sleep hygiene, medical and psychiatric disorders, sleep apnoea, periodic limb movements and restless leg syndrome. One key factor in the development of sleep disturbance in the nursing home is the environment, particularly with respect to high levels of night-time noise and light, low levels of daytime light, and care routines that do not promote sleep. Clinical assessment should include a comprehensive medical, psychiatric and sleep history including a review of prescribed medications. Nonpharmacological interventions for insomnia are underutilised in many clinical settings despite evidence that they are often highly effective.International studies suggest that 50–80% of nursing home residents have at least one prescription for psychotropic medication. Utilisation rates vary dramatically from country to country and from institution to institution. The most commonly prescribed medications for sleep are benzodiazepines and nonbenzodiazepine hypnotics (Z-drugs). The vast majority of studies of these medications are short-term, i.e. ≤2 weeks, although some longer extension trials have recently been carried out. Clinicians are advised to avoid long-acting benzodiazepines and to use hypnotics for as brief a period as possible, in most cases not exceeding 2–3 weeks of treatment. Patients receiving benzodiazepines are at increased risk of daytime sedation, falls, and cognitive and psychomotor impairment. Zaleplon, zolpidem, zopiclone and eszopiclone may have some advantages over the benzodiazepines, particularly with respect to the development of tolerance and dependence. Ramelteon, a novel agent with high selectivity for melatonin receptors, has recently been approved in the US. Use of the antidepressant trazodone for sleep in nondepressed patients is somewhat controversial. Atypical antipsychotics should not be used to treat insomnia unless there is also evidence of severe behavioural symptoms or psychosis. [ABSTRACT FROM AUTHOR]