Improved Sleep Continuity Research Articles

Comparison of Sleep and Mood in Patients After On-Pump and Off-Pump Coronary Artery Bypass Surgery

Off-pump coronary artery bypass surgical procedures have been advocated to reduce the adverse effects of cardiopulmonary bypass on the brain. To examine differences in objective and subjective characteristics of sleep and mood disturbance between patients after on-pump and off-pump coronary artery bypass surgery. In a secondary analysis of pooled data from 2 previous studies, sleep characteristics and mood disturbance on postoperative night 2 after transfer to the cardiac surgery step-down unit were compared in patients who had on-pump and off-pump cardiac surgery. The sample included 129 coronary artery bypass patients: 48 on-pump patients from one hospital and 81 off-pump patients from another hospital. Data were obtained with wrist actigraphs. Subjective characteristics of sleep were determined by using the Pittsburgh Sleep Quality Index and a sleep diary; mood disturbance was evaluated by using the short form of the Profile of Mood States. Off-pump surgery was associated with better objective sleep continuity (decreased percentage of wake time after sleep onset and fewer awakenings) but not longer sleep duration after controlling for age and sex. The 2 groups of patients did not differ overall in subjective sleep characteristics, mood disturbance, or preoperative sleep quality. Use of off-pump coronary artery bypass surgery may improve sleep continuity during the early postoperative period. Prospective longitudinal studies are needed to evaluate the potential long-term benefits of this procedure during the different phases of recovery.

Sleep-Stabilizing Effects of E-6199, Compared to Zopiclone, Zolpidem and THIP in Mice

Gamma aminobutyric acid (GABA)A receptor modulators constitute the majority of clinically used sedative-hypnotics. These compounds have the capacity to initiate and maintain sleep, but decrease REM sleep and delta activity within NREM sleep. In order to avoid such sleep adverse effects, the development of novel compounds remains of interest. The present study aimed at characterizing the acute effects of a novel putative hypnotic compound, E-6199, compared to zopiclone, zolpidem, and THIP on sleep-wakefulness patterns in mice. We also investigated whether repeated administration (daily injection during 10 days) of E-6199 was associated with tolerance and sleep disturbances at cessation of treatment. Polygraphic recordings were performed during 8 h after acute treatment with the various compounds. Under such conditions, E-6199 (5-20 mg/kg i.p.), zopiclone and zolpidem (2-10 mg/kg i.p.), but not THIP (2-10 mg/kg i.p.), exerted a marked sleep-promoting effect. Furthermore, E-6199 specifically increased the duration of NREM and markedly improved sleep continuity by lengthening NREM sleep episodes and reducing short awakenings and microarousal frequency. It also intensified NREM sleep by enhancing the slow wave activity within NREM at wake-NREM transitions. These effects were sustained and became even larger during chronic administration. Finally, abrupt E-6199 withdrawal did not elicit negative sleep effects. Our findings demonstrate that E-6199 may be an effective hypnotic compound that promotes and improves NREMS, without producing EEG side effects, tolerance or withdrawal phenomena, when administered under chronic conditions.

Exploratory Polysomnographic Evaluation of Pregabalin on Sleep Disturbance in Patients with Epilepsy

To evaluate the effects of adjunctive pregabalin 300 mg/day versus placebo on polysomnographic (PSG) variables in patients with well controlled partial seizures and subjectively reported sleep disturbance. An exploratory, 4-week, double-blind, randomized study in patients with well controlled partial seizures on AED monotherapy and subjective sleep disturbance over the previous 6 months. Mean changes from baseline to endpoint in PSG and subjective sleep variables (MOS Sleep Scale, Groningen Sleep Questionnaire) in patients on adjunctive pregabalin 300 mg/day (n=8) were compared with patients on placebo (n=7). Baseline PSGs showed sleep fragmentation. Mean sleep efficiency improved significantly in both treatment groups in the mean baseline to endpoint change; there was no significant between-group difference. Pregabalin treatment was associated with a significant reduction in number of awakenings (p = 0.02), and improvement in wake time after sleep onset approached significance (p = 0.055), suggesting improvement in sleep continuity that was not observed in the placebo group. Pregabalin was also associated with significant improvements in the MOS sleep disturbance and sleep quantity subscales compared with placebo (p < or =0.03). There were no changes in self-reported seizure control. This exploratory pilot study suggests that pregabalin may improve sleep continuity in patients with clinically relevant sleep disturbance. The effect on disturbed sleep appears independent of seizure control. The effects of pregabalin on disturbed sleep and seizures and their interrelationships warrant further study.

Major depressive disorder, sleep EEG and agomelatine: an open-label study

This open study evaluates the effect of agomelatine, a melatonergic receptor agonist and 5-HT2C antagonist antidepressant, on sleep architecture in patients suffering from major depressive disorder. Fifteen outpatients with a baseline HAMD score > or = 20 were treated with 25 mg/d agomelatine for 42 d. Polysomographic studies were performed at baseline, day 7, day 14, and day 42. Sleep efficiency, time awake after sleep onset and the total amount of slow-wave sleep (SWS) increased at week 6. The increase of SWS was predominant during the first sleep cycle. The amount of SWS decreased throughout the first four sleep cycles from day 7 and delta ratio increased from day 14 onwards. No change in rapid eye movement (REM) latency, amount of REM or REM density was observed and agomelatine was well tolerated. In conclusion agomelatine improved sleep continuity and quality. It normalized the distribution of SWS sleep and delta power throughout the night.

Effects of Neurapas® balance on sleep EEG, cognitive performance and mood: A double blind randomised cross-over study in healthy volunteers

Sleep disturbance is a major feature of patients with anxiety disorders and depression. Neurapas® balance is a triple herbal combination of extracts of St. John's wort (dry extract (DE) 60mg), valerian (DE 28mg) and passiflora (DE 32mg) that is widely used for treating minor depression in Germany. We tested the effect of Neurapas® balance on mood, sleep-EEG and cognitive performance in order to evaluate its central nervous effects in humans. 20 healthy subjects were examined twice in a double-blind, randomized completely balanced cross-over design and received either placebo or Neurapas® balance (3 days 3×2 tabl.). The dependent variables were sleep-EEG parameters, mood (BSKE) and vegetative symptoms (MSKL) and cognitive performance (TAP, ZVT, d2). Neurapas® balance significantly (compared to placebo) improved sleep continuity with a reduction of wakefulness. Non-REM-sleep was reduced in the first and significantly increased in the second sleep cycle and REM-latency was reduced. A positive trend was observed in regard to mental agitation and melancholy of the BSKE and hand-trembling and hand-moisture of the MSKL. No significant differences between Neurapas® balance and placebo were found in the cognitive performance tests. These findings show that Neurapas® balance has central nervous effects as reflected by changes in sleep EEG. It improves sleep continuity and subjective mood without negative effects on cognitive performance. The neurophysiological effects of Neurapas® balance® on the brain and the improved mood of the healthy volunteers is consistent with it having therapeutic effects in anxiety and depression with accompanying insomnia. Acknowledgement: This study was supported by Pascoe Pharmaceutische Preparations GmbH, Germany.

Effect of intrathecal baclofen on sleep and respiratory function in patients with spasticity

To prospectively evaluate the effect of pump-infused intrathecal baclofen infusion (ITB) in therapeutic doses on sleep quality and on daytime and nighttime respiratory function in patients with severe spasticity. We prospectively evaluated 20 consecutive patients (mean +/- SD age 45 +/- 13 years). We assessed spasticity and obtained polysomnography, pulmonary function tests, and resting energy expenditure measurements 1 week before and at least 8 days after pump implantation. Patients stopped oral baclofen upon pump implantation but continued other medications unchanged. We report descriptive statistics as means +/- SD. Most of the patients had multiple sclerosis (n = 9) or spinal cord injury (n = 8); there was one case each of cerebral palsy, hereditary spastic paraplegia, and Friedreich ataxia. Before and after ITB initiation, mean Ashworth scores were 2.75 +/- 0.85 and 1.15 +/- 0.36, and mean spasm scores were 3.75 +/- 0.55 and 1.00 +/- 0.56. ITB improved total sleep time (p = 0.05) and sleep efficiency (p = 0.01) and reduced periodic leg movements (p = 0.02). ITB did not modify sleep-related respiratory events, lung function tests, CO2 rebreathing response, or resting energy expenditure. Compared with oral baclofen, intrathecal baclofen infusion did not affect respiratory function and improved sleep continuity. Intrathecal baclofen infusion in therapeutic doses may act at the spinal level rather than at the supraspinal level.

REM-Sleep in patients with dementia of Alzheimer and frontotemporal type under long term treatment with cholinesterase inhibitors

Besides cognitive impairment, patients with dementia commonly present with a sleep disturbance. The most robust polysomnographic finding in Alzheimer’s dementia (DAT) is reduction of REM-sleep. Cholinsterase inhibitors (Che-I) are able to increase REM-sleep in volunteers. The objective of this study was to evaluate the effects of Che-I on REM-sleep in DAT and frontotemporal dementia (FTD) during long-term treatment. So far, 13 patients with low to moderate dementia could be examined. 7 patients were classified as having DAT and 6 patients as having FTD. A polysomnography was performed in all patients who were free of psychotropic medication before therapy with a Che-I and after 5–10 months, while patients were on monotherapy with a Che-I. In all patients sleep continuity disruption was observed. In DAT a more accentuated REM sleep reduction in comparison to FTD was found. Treatment with Che-I did not improve sleep continuity. However, REM-sleep increased in patients with DAT, but not in patients with FTD. Furthermore, REM-latency was reduced in DAT after treatment with Che-I. The observed REM-sleep reduction in patients with DAT compared to FTD may suggest that cholinergic neurotransmission is more impaired in DAT than in FTD. However, it remains unclear whether the increase of REM-sleep after long-term treatment with Che-I in DAT may only reflect a mere pharmacological effect or whether this increase may be related to the efficacy of anti-dementia treatment

Improved Sleep Continuity and Increased Slow Wave Sleep and REM Latency During Ziprasidone Treatment

Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.

The interaction between sleep and thermoregulation in adults and neonates.

The interaction between sleep and thermoregulation leads to different thermoregulatory responses depending on the sleep stage and alterations in sleep when in a cool or warm environment. In the human adult, differences in thermoregulatory efficiency during rapid eye movement (REM) sleep and slow wave sleep (SWS) are less pronounced compared to other mammals: although thermoregulatory processes persist in REM sleep, they are less efficient than during SWS. Cold and warm loads disturb the efficiency and structure of sleep. The duration of REM sleep and (to a lesser extent) of SWS decreases. In contrast, pre-sleep warm loads enhance SWS and improve sleep continuity. This procedure may promote and maintain sleep in depressed patients, whose sleep and body temperature rhythms are modified. In contrast to adults, homeothermic processes in neonates are maintained or even enhanced during active sleep (AS) when compared to quiet sleep (QS). Sleeping in a cool environment increases the duration of AS at the expense of QS. As a result, the thermoregulatory function overcomes the need to conserve energy that would otherwise lead to increased QS. An interaction between sleep, respiration, and thermoregulation may be involved in Sudden Infant Death Syndrome: an alteration in the thermal balance may perhaps induce respiration instability, especially during AS.

Effects of clozapine on sleep measures and sleep-associated changes in growth hormone and cortisol in patients with schizophrenia

There have been limited reports on the effect of the atypical anti-psychotic agent clozapine on sleep measures and hormone secretion. The goal of this study was to determine the type, rate, and extent of changes in sleep measures and nighttime secretion of growth hormone (GH) and cortisol during clozapine treatment. Five schizophrenic patients (age: 32.4±7.4) and five age- and sex-matched normal subjects (age: 33.0±5.1) underwent nocturnal polysomnography (NPSG) before clozapine therapy (S1), and during early and late clozapine therapy (S2 and S3). Serum GH and cortisol levels were monitored during each NPSG. NPSG findings showed that the mean total sleep time, sleep efficiency, and duration of awakening were increased at S2, and maintained until S3. The mean amounts of stage 2 sleep at S2 and S3 increased significantly compared with that of S1. In unmedicated schizophrenic patients, the mean plasma GH level in rapid eye movement sleep was lower than during the waking stage, and the mean level of plasma cortisol was higher during the waking stage. Plasma cortisol levels did not differ between control subjects and patients at any time, but clozapine treatment decreased plasma cortisol levels at S2 compared with S1 and S3. Plasma GH levels were unchanged by clozapine treatment. Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy. These effects were maintained through at least 7 weeks of therapy. However, clozapine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients.

Medical management of obstructive sleep apnea

The last 20 years have seen remarkable gains in our understanding of the pathophysiology of sleep-disordered breathing. The rapid growth in both scientific and clinical knowledge has been fueled by the development of nonsurgical therapies for obstructive sleep apnea (OSA). These medical therapies have provided the avenue for public acceptance of the diagnosis and treatment of this common medical condition. However, medical therapy requires active patient participation, to achieve the desired outcomes of improved sleep continuity, daytime functioning, and quality of life. Conservative therapies, such as weight loss and patient positioning; and pharmacological therapies, have been disappointing. Positive pressure therapy has become the treatment of choice for the vast majority of OSA patients. Oral appliances offer an acceptable treatment alternative for select patients. Present research indicates that these mechanical approaches can produce significant decreases in the frequency and severity of sleep-disordered breathing and nocturnal oxyhemoglobin desaturation. Preliminary data from ongoing studies suggest that these interventions will reduce long-term morbidity and possibly mortality. Copyright © 1999 by W.B. Saunders CompanyProgress in Cardiovascular Diseases, Vol. 41, No. 5 (March/April), 1999: pp 377-386

Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder

Background: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency; in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep. Methods: This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone ( n = 64) with fluoxetine ( n = 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1–4, 6, and 8. Results: Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine. Conclusions: Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician- and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consstent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action.

Effects of clozapine on sleep: A longitudinal study

Polysomnographic studies on the effects of clozapine, an atypical antipsychotic agent with strong sedative properties, on night sleep report inconsistent results. Most of these studies did not include baseline recordings and were not controlled for clozapine-induced fever, which is known to alter nocturnal sleep. We conducted a 2-week longitudinal polysomnographic investigation in 10 long-term drug-free schizophrenic patients prior to and at the end of the first and second weeks of clozapine treatment. Rectal temperature was measured daily and patients with fever (> 37.9 degrees C) were excluded. Clozapine significantly improved sleep continuity. In addition, non-rapid eye movement (NREM) sleep and in particular stage 2 sleep increased significantly, while the amounts of stage 4 and slow-wave sleep decreased significantly. Clozapine increased significantly REM density, but it did not affect the amount of REM sleep. We conclude that in patients who do not experience clozapine-induced fever, clozapine has strong sleep consolidating effects resulting from an increase in stage 2 NREM sleep.

A randomized, double-blind trial of the efficacy and cost-effectiveness of clozapine

Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

Effect of pharmacologic treatments on the sleep of depressed patients

Antidepressant drugs produce striking effects on sleep architecture that are best understood in terms of their interactions with the monoamine pathways controlling sleep and wakefulness. Many different antidepressant drugs, including tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective 5-hydroxytryptamine (5-HT; serotonin) reuptake inhibitors (SSRIs), decrease rapid eye movement (REM) sleep. The reduction in REM sleep produced by antidepressants may be an important part of their mechanism of action; however, the ability of new antidepressant compounds, such as nefazodone and moclobemide, to increase REM sleep throws doubt on this suggestion. The effects of antidepressants on slow-wave sleep (SWS) are quite diverse; in general, antidepressants having significant 5-HT2A/2C receptor antagonist properties increase SWS, whereas other drugs, such as SSRIs or MAOIs, either lower SWS or produce no change. Sleep continuity is improved acutely following administration of antidepressants with sedating properties such as certain TCAs, trazodone, and mianserin. Some nonsedating drugs (ritanserin and nefazodone) also improve sleep continuity measures, possibly through 5-HT2A/2C receptor blockade.