Lower doses of sublingual Zolpidem are more effective than oral Zolpidem to anticipate sleep onset in healthy volunteers

ObjectiveTo compare the efficacy of sublingual Zolpidem (5 and 10 mg) to conventional oral Zolpidem (10 mg).MethodsThis was an open, randomized, double-blind, double-dummy, controlled, and single center study. The study took place at the Laboratory of Clinical Neurophysiology and total number of participants was 58 volunteers completed the study whose demographics of age, gender, body mass index (BMI) were similar among everyone. Scores in Epworth, Pittsburgh, Beck and Hamilton Scales did not differ among groups. A model of transient insomnia was determined by the sleep anticipation in 120 minute. Subjects were randomly divided in three groups for drug administration (5 m SL; 10 mg SL and 10 mg oral), given in a single dose prior to polysomnography (PSG). Sleep parameters were assessed by PSG and post-sleep questionnaires.ResultsA significant main treatment effect was evident considering the sleep onset latency (SOL) and persistent sleep latency (PSL). An earlier sleep onset was induced by SL Zolpidem 10 mg (SOL = p < 0.004; PSL = p < 0.006) and SL Zolpidem 5 mg (SOL = p < 0.025; PSL = p < 0.046) compared to oral Zolpidem 10 mg. Subjects that received SL Zolpidem 10 mg reported an earlier sleep onset (latency to sleep and latency until persistent sleep) when compared to subjects from other groups (p < 0.005).ConclusionsSublingual Zolpidem, both 5 and 10 mg, induced faster sleep initiation than 10 mg oral Zolpidem. A subjective perception of earlier sleep onset was reported by subjects using SL 10 mg.     

Sleep characteristics of menopausal insomnia: a polysomnographic study

Although menopausal insomnia is of clinical significance, the essential features of this form of disrupted sleep are poorly understood. The aim of the present study was to identify the sleep characteristics of menopausal insomnia by using overnight polysomnography (PSG). Twenty-one subjects with menopausal insomnia (MI) and 13 sex- and age-matched normal control (NC) subjects without sleep complaints took part in the present study. All MI and NC subjects underwent PSG on two consecutive nights. In comparison with NC, MI subjects had non-specific findings such as significantly shorter total sleep time, longer sleep latency, higher wake time after sleep onset, and lower sleep efficiency. As for rapid eye movement (REM) sleep variables, MI subjects had significantly shorter total REM sleep time, fewer numbers of REM sleep periods, longer REM latency, and higher REM density than did the NC subjects. As for the time course of REM density, REM density during the first 3 h period of nocturnal sleep was significantly higher for MI than for NC subjects. Unlike NC subjects, REM density for MI subjects did not tend to rise progressively during nocturnal sleep. The MI subjects had objective evidence of disrupted sleep and the most striking characteristics of this dysfunction were observed in REM sleep variables. The sleep characteristics of MI subjects were found to differ in REM sleep variables from those of patients with major depression (except for REM density). Menopausal insomnia patients appear to be similar to patients with generalized anxiety disorder accompanied by severe sleep disruption. These data lend support to the clinical distinction between menopausal insomnia and insomnia associated with major psychiatric disorders.     

Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study

In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.     

Good sleep, bad sleep: a meta-analysis of polysomnographic measures in insomnia, depression, and narcolepsy.

Primary insomnia, major depression, and narcolepsy are usually considered to be separate disorders, distinguished by different polysomnographic profiles. But do polysomnographic data provide adequate evidence to segregate the three disorders, or might they display fundamentally the same sleep disturbance, differing only in degree? To test the viability of these two alternate hypotheses, the authors performed a meta-analysis of controlled polysomnographic studies of these disorders. A summary measure of degree of sleep disturbance was constructed from five variables: wakefulness after sleep onset, percentage of stage 1 sleep, percentage of stage 3 + 4 sleep, rapid eye movement (REM) latency, and REM density. The results of available studies for each variable were combined using a weighted average of effect sizes. An overall "sleep disturbance index" was then calculated by combining the estimates for the five above listed variables. On both the individual measures and especially on the summary index, insomnia, depression, and narcolepsy were arrayed on a simple continuum of progressively more severe sleep disturbance--congruent with the clinical observation that these disorders display progressively more disturbed sleep. These findings suggest that sleep can be disturbed in only a limited number of ways: in evaluating sleep architecture, it may not be possible to elaborate much beyond a single axis of good-to-bad sleep. Thus, polysomnographic measures may not provide adequate evidence to classify insomnia, depression, and narcolepsy as separate entities.     

Sertraline is more effective than imipramine in the treatment of non-melancholic depression: results from a multicentre,randomized study

The acute treatment efficacy, tolerability, and effects on health-related quality of life of sertraline (50-200 mg/day) versus imipramine (75-225 mg/day) were compared in outpatients with non-melancholic depression. The study employed an open-label, parallel-group design. One hundred and sixteen patients were randomized to receive sertraline and 123 to receive imipramine for 8 weeks. In the intent-to-treat (ITT), last-observation-carried-forward (LOCF) analysis, sertraline produced statistically significantly greater improvements in depressive (21-item Hamilton Depression Rating Scale [HAM-D(21)] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint, P<.005) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9, P<.01), as well as in response (69.0% versus 53.7% at endpoint, P=.016) and remission rates (51.3% versus 38.0% at endpoint, P=.041) from week 4 onwards compared with imipramine. The proportion of patients who were 'very much improved' or 'much improved' (Clinical Global Impressions Scale of Improvement [CGI-I] score of 1 or 2) was significantly higher at endpoint in the sertraline group (76.1%) than in the imipramine group (62.8%) (P=.028). At week 8, patients in both treatment groups showed clear improvements in quality of life, although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients. Sertraline was significantly superior in tolerability with less discontinuations due to adverse events (10.3%) compared with the imipramine group (24.4%) (P=.004). It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression.     

Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients

ObjectiveMelatonin plays a key role in the proper functioning of the circadian timing system (CTS), and exogenous melatonin has been shown to be beneficial in cases of CTS and sleep disturbances. Nevertheless, the concept of “melatonin deficit” has yet to be defined. The aim of our study was, therefore, to determine the relationship between the degree of pineal calcification (DOC) and a range of sleep parameters measured objectively using polysomnography (PSG).MethodsA total of 31 outpatients (17 women, 14 men, mean age 45.9 years; SD 14.4) with primary insomnia were included in our study. Following an adaptation night, a PSG recording night was performed in the sleep laboratory. Urine samples were collected at predefined intervals over a 32-h period that included both PSG nights. The measurement of 6-sulphatoxymelatonin (aMT6s) levels was determined using ELISA. DOC and volume of calcified pineal tissue (CPT) and uncalcified pineal tissue (UPT) were estimated by means of cranial computed tomography.ResultsUPT was positively associated with 24-h aMT6s excretion (r = 0.569; P = 0.002), but CPT was not. After controlling for age, aMT6s parameters, CPT, and UPT did not correlate with any of the PSG parameters evaluated. In contrast, DOC was negatively associated with REM sleep percentage (r = ?0.567, P = 0.001), total sleep time (r = ?0.463, P = 0.010), and sleep efficiency (r = ?0.422, P = 0.020).ConclusionDOC appears to be a superior indicator of melatonin deficit compared to the absolute amount of melatonin in the circulation. High DOC values indicate changes predominantly in the PSG parameters governed by the circadian timing system. DOC may thus serve as a marker of CTS instability.     

Disturbed sleep in children with Tourette syndrome: a polysomnographic study

OBJECTIVE: To evaluate objective data on sleep quantity/quality and motor activity during night sleep in children with Tourette syndrome (TS). METHOD: Polysomnography of 17 unmedicated TS children (ages: 7;11-15;5, mean: 11;10 years) without comorbid attention-deficit hyperactivity disorder (ADHD) was compared with 16 age-, sex- and IQ-matched healthy controls. Sleep analyses according to the procedure of Rechtschaffen and Kales were supplemented by counting epochs with short arousal-related movements (相似文献   

Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study

BACKGROUND: Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. METHOD: Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. RESULTS: In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment. Patients rated sleep quality (p < or = .001) and working ability (p < or = .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No significant group differences in side effects were found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). CONCLUSION: The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.     

Sex differences in the polysomnographic sleep of young adults: a community-based study

BACKGROUND AND PURPOSE: In small, clinical samples, men have reduced slow wave sleep compared to women. Given the higher prevalence of sleep-related breathing disturbance in men, this study assessed sex differences in sleep in a large, non-clinical sample of adults and controlled for primary sleep disorders. PATIENTS AND METHODS: Men and women, 31-40 years old, drawn from a longitudinal sample representative of southeast Michigan served as subjects. Each underwent a sleep study consisting of two consecutive 8-h nights of standard polysomnography (NPSG) and a multiple sleep latency test (MSLT) the intervening day. RESULTS: Of the 439 eligible participants, 292 (66.5%) agreed to spend two consecutive nights and the intervening day in the sleep laboratory. Standard polysomnograms that monitored respiration and leg movements were collected each night, and on the intervening day the MSLT was performed. Men had more sleep-related breathing disturbance than women. After adjusting for this higher prevalence of respiratory disturbance, men still had a lower mean sleep efficiency (i.e. increased wake time) and a higher percentage of stage 1 sleep. Men and women did not differ in most other sleep parameters and did not differ in level of daytime sleepiness on the MSLT. CONCLUSIONS: Sleep-related respiratory disturbance accounted for some of the sex differences in sleep. After correcting for respiratory disturbance, men still had lighter and less efficient sleep, but this was not associated with greater daytime sleepiness. Whether this reflects a sex difference in the functioning of the sleep homeostat will require further study.     

Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial

To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to receive either 5-mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively followed by a 4-week treatment period. After that period, treatment was continued if the parents wished so. The study's impact was assessed by measurements of lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33). Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light melatonin onset was measured in saliva (n = 27). Sustained attention was evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62) minutes. In the placebo group, these parameters did not shift significantly. The change during the 4-week treatment period differed between the treatment groups significantly as to lights-off time, diary and actigraphic sleep onset, sleep duration, and melatonin onset. There were no significant differences between the treatment groups in the change of sleep latency, wake-up time, and sustained attention reaction times. Mild headache occurred in 2 children during the first 2 days of the melatonin treatment. Eighteen months after the start of the trial, in 13 of the 38 children who could be followed up, melatonin treatment was stopped because their sleep problem was solved and in 1 child because sleep was not improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child developed mild generalized epilepsy 4 months after the start of the trial. The results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the short term and significantly more effective than placebo in advancing sleep onset and dim light melatonin onset and increasing sleep duration in elementary school children with chronic sleep onset insomnia. Sustained attention was not affected.     

The effect of baclofen on objective and subjective sleep measures in a model of transient insomnia

Study objectivesInsomnia is a common medical complaint. Current pharmacologic treatments have modest efficacy and numerous side effects. Baclofen is a gamma-aminobutyric acid (GABA)b receptor agonist used to treat spasticity in various medical conditions. Several studies noted that baclofen, when used to treat sleep related disorders, resulted in improvement in sleep parameters. Measures of insomnia, however, were not assessed in those studies. To date, baclofen has not been assessed for efficacy in the treatment of insomnia.MethodsWe randomized 20 healthy subjects to baclofen or placebo in a cross over design. All subjects underwent two polysomnograms (PSG) assessing sleep parameters. Baclofen or placebo was given 90 min prior to lights out in random order for each subject. Lights out occurred two hours earlier than the subject's median habitual bedtime.ResultsBaclofen resulted in significantly less objective wake after sleep onset and stage 1 sleep, and significantly increased total sleep time (TST), sleep efficiency, and stage 3/4 sleep. There was no effect on sleep onset latency (SOL). Self-report variables indicated significantly less subjective awakenings from sleep and increased subjective sleep quality. There was no effect on subjective TST or subjective SOL.ConclusionsThis study showed that baclofen was superior to placebo with regard to several objective and subjective measures used to assess sleep quality. These data support the notion that baclofen shows promise as an effective hypnotic drug.     

Spectral analysis of the sleep onset period in primary insomnia

ObjectiveTo compare the EEG power spectra characteristics of the sleep onset period (SOP) in patients with sleep onset insomnia (SOI), sleep maintenance insomnia (SMI) and good sleepers (GS).MethodsThe time course of EEG power density (1–40 Hz) during the SOP was examined in thirty subjects (SOI patients: N = 10, SMI patients: N = 10, GS: N = 10).ResultsThe EEG power of the beta2 frequency band (18–29.75 Hz) was significantly lower in SOI than in SMI in the period preceding sleep onset. The alpha power was significantly higher for the SMI group compared to GS before sleep onset. Despite the lack of statistical significance, several differences in EEG dynamics were observed in SOI compared to two other groups: delta power increased slower after sleep onset; beta2 and 3 (18–29.75 and 30–39.75 Hz) power decrease less abruptly before sleep onset; beta1 (15–17.75 Hz) power increase through the whole SOP.ConclusionsThe lower level of beta2 frequency band in SOI and the differences in dynamics in delta and beta bands may suggest that a mechanism other than hyperarousal participates in etiology of SOI.SignificanceSOI and SMI patients have different spectral characteristics in SOP, thus future studies should avoid the inclusion of mixed insomnia samples.     

Repetitive thought is associated with both subjectively and objectively recorded polysomnographic indices of disrupted sleep in insomnia disorder

BackgroundRepetitive thought is a hallmark of several psychopathological conditions and in particular a perpetuating and maintaining factor in Insomnia Disorder. Accordingly, one of the primary complaints reported by Insomnia patients is the inability to shut-off or control thoughts. Worry and rumination are the two best-known styles of repetitive thought leading to sleep disturbances. The aim of this study was to investigate the relationship of these two cognitive processes on nocturnal sleep indices objectively recorded by polysomnography.Methods27 Insomnia patients and 20 healthy controls matched for sex and age were recruited and completed a comprehensive assessment aimed to evaluate sleep quality, excessive daytime sleepiness, insomnia severity, worry, rumination, depressive and anxious symptomatology, and the ability to produce reasonable cognitive estimates. Sleep diaries indices and polysomnographic recordings were evaluated.ResultsInsomnia patients showed increased levels of worry and rumination in comparison to controls. Our polysomnographic study revealed that these two different types of repetitive thoughts were significantly associated with objective sleep variables. In particular, heightened worry levels were related to an augmented wake after sleep onset and diminished total sleep time, sleep efficiency and percentage of REM sleep, whereas rumination was associated with an increase of sleep latency and a decrement of sleep efficiency. However, after controlling for anxiety and depressive symptoms only worry maintained a significant relationship with polysomnographic variables. Remarkably, repetitive thoughts did not correlate with microstructural REM sleep features and quantitative EEG analysis.ConclusionOur study indicates the existence of a significant relationship between daytime levels of repetitive thought and sleep, thus corroborating the hypothesis of an interplay between cognitive and nocturnal electrophysiological activity in insomniacs.     

Fatal familial insomnia: a model disease in sleep physiopathology

Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal signs, myoclonus, dysarthria/dysphagia, ataxia). Positon emission tomography (PET) disclosed thalamic hypometabolism and milder involvement of the cortex; neuropathology severe neuronal loss in the thalamic nuclei variably affecting the caudate, gyrus cinguli and fronto-temporal cortices. Genetic analysis disclosed a mutation in the PRNP gene and FFI was transmitted to experimental animals, thus classifying FFI within the prion diseases. Rare Sporadic Fatal Insomnia (SFI) cases occur without PRNP mutation but with features similar to FFI. FFI represents a model disease for the study of sleep-wake regulation: (I) the profound thalamic hypometabolism/atrophy associated with lack of sleep spindles and delta sleep implicate the thalamus in the origin of slow wave sleep (SWS); (II) loss of SWS is associated with marked autonomic and motor hyperactivity; termed 'agrypnia excitata', this association has been proposed as a useful clinical concept representative of thalamo-limbic dysfunction; (III) lack of SWS occurs with substantial preservation of stage 1 NREM sleep, implying that the latter has mechanisms different from SWS and unaffected by thalamic atrophy; accordingly, conflating stage 1 NREM with SWS into NREM sleep is inappropriate.     

Morning headaches in patients with sleep disorders: a systematic polysomnographic study

OBJECTIVES: Patients with sleep disorders suffer more often from headache after awakening than healthy subjects. However, it still is a matter of controversy whether this applies only to patients with sleep apnea syndrome (SAS) or also to patients with other diagnoses of sleep disorders. METHODS: We asked all patients in our sleep laboratory about the frequency of past headaches and also ascertained the occurrence of morning headaches after awakening in the sleep laboratory. Polysomnographic recordings from nights before morning headache were compared with nights without following headache. Four hundred and thirty-two patients with sleep disorders (age range 18-86 years, 37% women) and 30 healthy subjects (age range 24-55 years, 27% women) participated in this prospective study. RESULTS: The reported frequency of past headaches and the frequency of morning headache in the sleep laboratory were significantly increased in patients with SAS and other sleep disorders compared with healthy subjects. The occurrence of morning headache in the sleep laboratory was associated polysomnographically with a decrease in total sleep time, sleep efficiency and amount of rapid eye movement sleep and with an increase in the wake-time during the preceding night. CONCLUSIONS: We conclude that morning headaches in patients with sleep disorders might be associated with particular disturbances of the preceding night's sleep. We speculate that dysregulation in anatomically identical central regions modulating sleep and nociception might be relevant to morning headache, rather than one particular sleep disorder such as SAS.