European guideline for the diagnosis and treatment of insomnia

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Are questionnaires reliable in diagnosing sleep-disordered breathing in university students?

OBJECTIVE: This study aimed to screen young adults for sleep-disordered breathing, and compare those with high and low risk for sleep-disordered breathing. METHODS: A survey based on the Berlin questionnaire was completed by 330 university students, and the results were used to divide them into sleep-disordered breathing positive and sleep-disordered breathing negative groups. A representative group was selected from each cohort (positive group, n = 16; negative group, n = 21), and assessed with sleep study, ENT examination, the Nose Obstruction Symptom Evaluation scale, and the Epworth Sleepiness Scale. RESULTS: Sleep-disordered breathing prevalence was 11.2 per cent in the questionnaire and 24 per cent according to the sleep study. The sleep-disordered breathing positive and negative groups significantly differed in terms of coexisting sleep-disordered breathing symptoms. There were no significant differences between the positive and negative groups with regard to sleep study parameters (apnoea/hypopnoea index, respiratory disturbance index, oxygen desaturation index, snoring intensity) and the Epworth Sleepiness Scale. CONCLUSION: Subjective and objective diagnostic tools revealed that sleep-disordered breathing is a common problem among young adults.

Increased severity of sleep-disordered breathing is associated with insomnia and excessive somnolence in primary school children.

OBJECTIVE: The aim of the study was to investigate the prevalence of difficulty with initiation or maintenance of sleep (DIMS) and excessive daytime sleepiness (EDS) in a general pediatric population, and to evaluate the relationship between these conditions and sleep-disordered breathing (SDB) symptom intensity. METHODS: This population-based cross-sectional study from 27 primary schools in a medium-sized city in Poland was based on use of a questionnaire regarding demographic data, symptoms of SDB, DIMS, and EDS. Data were collected between September and December 2014. In all, 2940 caregivers were recruited and were asked to fill-out questionnaires and written consent. RESULTS: A total of 68% of the questionnaires (n = 1987) were returned and analyzed. Habitual snoring (HS) was reported in 104 (5.3%) children. DIMS and EDS were seen in 137 children (6.9%) and 117 children (5.9%), respectively. The prevalence of DIMS increased from 3.5% in children who never snored to 28.6% in children who snored very often or always. Similarly, the prevalence of EDS was 2.7% in children who did not snore and increased to 19% in children who snored very often or always. No correlation was seen between increasing DIMS (r = 0.006, p > 0.05) or EDS (r = -0.031, p > 0.05) scores and body mass index. CONCLUSIONS: This study is the first to measure the symptoms of both DIMS and EDS in a general pediatric population and to assess the relationship between both DIMS and EDS and SDB in children. We found that children with more frequent snoring had a higher prevalence of DIMS as well as EDS; however, there was no correlation between body mass index and either DIMS or EDS symptom severity.

Social and nonsocial affective processing in schizophrenia - An ERP study.

BACKGROUND: Despite social cognitive dysfunction that may be observed in patients with schizophrenia, the knowledge about social and nonsocial affective processing in schizophrenia is scant. The aim of this study was to examine neurophysiological and behavioural responses to neutral and negative stimuli with (faces, people) and without (animals, objects) social content in schizophrenia. METHODS: Twenty-six patients with schizophrenia (SCZ) and 21 healthy controls (HC) completed a visual oddball paradigm with either negative or neutral pictures from the Nencki Affective Picture System (NAPS) as targets while EEG was recorded. Half of the stimuli within each category presented social content (faces, people). RESULTS: Negative stimuli with social content produced lower N2 amplitude and higher mean LPP than any other type of stimuli in both groups. Despite differences in behavioural ratings and alterations in ERP processing of affective stimuli (lack of EPN differentiation, decreased P3 to neutral stimuli) SCZ were still able to respond to specific categories of stimuli similarly to HC. CONCLUSIONS: The pattern of results suggests that with no additional emotion-related task demands patients with schizophrenia may present similar attentional engagement with negative social stimuli as healthy controls.

Genetics of rapid eye movement sleep in humans.

The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases.

Low Risk for Switch to Mania during Treatment with Sleep Promoting Antidepressants.

INTRODUCTION: Sleep-promoting antidepressants are of interest because they are used not only as antidepressants, but also to promote sleep. METHODS: We reviewed case reports describing the switch to mania during treatment with trazodone, mirtazapine, or agomelatine. RESULTS: Trazodone, mirtazapine, and agomelatine may induce manic symptoms. However, the risk of switching is related, first of all, to doses recommended for antidepressant treatment, administered without mood-stabilizer co-therapy. Low doses of these antidepressants, used for their hypnotic or sedative effects, were observed to cause mania only in patients with other risk factors for switching. There is no evidence for trazodone or mirtazapine and only sparse evidence for agomelatine, claiming that treatment with these antidepressants is related to an increased risk of switching to mania when administered in combination with a mood stabilizer. DISCUSSION: These findings suggest that low doses of trazodone and mirtazapine are safe in bipolar disorder, and should still be considered important alternatives to hypnotics when long-term pharmacological treatment of insomnia is necessary. It seems that these antidepressants and agomelatine can also be used safely in antidepressant doses when combined with a mood stabilizer.

Sleep disorderd breathing and recurrence of cerebrovascular events, case-fatality, and functional outcome in patients with ischemic stroke or transient ischemic attack.

Ninety one patients with stroke or transient ischemic attack (TIA) were screened for sleep-disordered breathing (SDB). Case fatality, rate of recurrence of cerebrovascular events, and functional outcome were analyzed during a 2-year follow-up. The patients were stratified into groups: without (AH < or =5) and with SDB (AHI >5). SDB was present in 61 (67.7%) patients with stroke or TIA. The rate of recurrence of TIA or stroke in patients with SDB was significantly higher (12 patients, OR=1.52, P<0.05) as compared with patients without SDB (3 patients) within two years of observation. Case-fatality rates were not significantly different (4 patients with SDB and 2 patients without SDB). Our data show that SDB significantly increases the incidence of recurrent cerebrovascular events in patients with TIA or stroke in a two-year follow-up. SDB in patient with stroke or TIA did not influence functional outcome of stroke during the long-term observation.

Sleep related breathing disorders in patients with ischemic stroke and transient ischemic attacks: respiratory and clinical correlations.

Fifty five patients with ischemic stroke and 15 patients with transient ischemic attacks (TIA) were screened for sleep related breathing disorders (SRBD). Apnea-hypopnea index (AHI) and desaturation index (DI) were analyzed. The clinical status was assessed with National Institute of Health Stroke Scale (NIHSS). The patients with stroke were stratified into groups: without (AHI10). SRBD were present in 36 patients with stroke and in 10 patients with TIA. There were significant differences in the clinical status on admission, as quantified with NIHSS, between stroke patients with mild and moderate or severe SRBD. AHI positively correlated with NIHSS on admission in stroke patients (r=0.54, P<0.01). The final NIHSS score was significantly greater in patients with moderate or severe SRBD than in those with mild SRBD: 3.4+/-1.9 and 1.8+/-1.2, respectively. Our data suggest that the severity of SRBD is related to the clinical status on admission and it influence the clinical outcome after ischemic stroke.

The incidence of sleep apnea in patients with stroke or transient ischemic attack.

Disorders of breathing during sleep are defined as cessation or reduction of air flow thorough the upper airway, accompanied by a decrease of oxygen saturation. The results of many studies underline the association between sleep-disordered breathing (SDB) and cerebrovascular disorders. SDB, mostly obstructive sleep apnea syndrome (OSAS), is believed to be an independent risk factor of stroke and is related to poor outcome and increased long-term stroke mortality. The present study evaluated the frequency of SDB in patients with stroke or transient ischemic attack transient ischemic attack. We studied 43 patients (mean age 68.5 +/-11.0), which included 35 males and 8 females, with acute stroke (n=37) and transient ischemic attack (n=6). The assessment included body mass index (BMI), age, cardiovascular risk factors, and localization of stroke. All patients underwent all-night screening for SDB with a portable 8-channel recorder. The apnea/hypopnea index (AHI) for the whole group was 13.3 +/-15.2. AHI <5 was found in 16 patients. Overall, SDB was present in 27 (62.8%) patients with stroke and transient ischemic attack, stratified into those with AHI 5-10, (10 patients), 10-20 (8 patients), and AHI>20 (9 patients). In 15 patients, there was an increase in AHI >or=5 on assuming the supine position. The patients' mean BMI was 27.8 +/-4.7. The analysis of BMI, age, and localization of stroke was not sufficient to identify patients with high risk for SDB. We submit that overnight screening for SDB should be routinely performed in every patient after stroke and transient ischemic attack and it should become a diagnostic tool in neurological departments.

Spectral composition of NREM sleep in healthy subjects with moderately increased daytime sleepiness.

OBJECTIVE: This study addressed the relationship between daytime sleepiness and spectral composition of the preceding NREM sleep. METHODS: Nineteen healthy volunteers (mean age: 36.5 years; SD: 10.1) underwent polysomnography during two consecutive nights and the multiple sleep latency test (MSLT) on the following day. Daytime sleepiness was also assessed by the Epworth sleepiness scale (ESS). The sleep recordings were visually scored according to standard criteria. The quantitative sleep EEG analysis was performed using a fast Fourier transform routine. The sleep parameters were compared between subjects with short and long MSLT sleep latencies (cut-off=10 min) and between subjects with low and high ESS scores (cut-off=6 points). RESULTS: Subjects with short MSLT sleep latencies showed a reduced theta EEG activity. There was no evidence of reduced synchronization of sleep EEG in subjects with high ESS scores. CONCLUSIONS: Moderately increased daytime sleepiness as indicated by MSLT sleep latency less than 10 min is accompanied by decreased power of theta activity during NREM sleep indicating a deficit of sleep EEG synchronization.

Ghrelin promotes slow-wave sleep in humans.

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.

Rhythmic feet movements while falling asleep.

During the wake-sleep transition and sleep, diverse motor phenomena such as hypnagogic foot tremor may occur in the lower extremities. We investigated the relevance of this phenomenon in 375 consecutive subjects examined polysomnographically in a sleep disorders center. Rhythmic feet movements while falling asleep (RFM) were found in 28 subjects (7.5%). RFM occurred mostly as single, short series with a duration of between 10 and 15 seconds. They had a high night-to-night variability and were detected as rhythmic, oscillating movements of the whole foot or toes. Surface electromyographic (EMG) recordings displayed series of repetitive phasic bursts with a periodicity mostly between 1 and 2 per second. Single EMG burst duration varied between 300 and 700 msec. RFM at highest intensity occurred during presleep wakefulness, and usually persisted in sleep stages 1 and 2. RFM did not have a major sleep-disturbing effect in any of the affected subjects. Due to its high prevalence and the lack of a major sleep-disturbing effect, short series of RFM could be considered a quasiphysiological phenomenon. However, in more severe forms of RFM with evidence of a sleep-disturbing effect, RFM should be considered abnormal.

Comparison between eye movement latency and REM sleep parameters in major depression.

Alterations of sleep can be observed polysomnographically in approximately 90 percent of depressed patients. Most of the registered sleep abnormalities in depression also occur in other psychiatric disorders. Only some types of REM sleep alterations-- short REM latency, increase of REM density and shortening of mean latency of eye movements--were reported as more specific for affective disorders. In the present study polysomnograms of 21 medication free patients with major depressive disorder (assessed with a structured interview for DSM-III-R and Hamilton Scale) and 21 healthy controls were analysed. REM latency (LREM), REM density (RD), latencies of eye movements (LEM) and mean latency of eye movements (M-LEM) were calculated for both groups. Depressed patients (compared with healthy controls) showed increased RD (38.2% vs. 28.2%, p < 0.0001), shortened M-LEM (35.7 s vs. 48.3 s, p < 0.04) and shortening of LEM in the 1st (28.9 s vs. 48.9 s, p < 0.007) and 4th (27.0 s vs. 59.1 s, p < 0.043) REM sleep periods. LREM was not shortened significantly in depressives (78.5 min vs. 91.3 min, ns). In healthy subjects a negative correlation between M-LEM and RD was found (rho = -0.47, p < 0.03). Since in the current study depressed patients differed from healthy controls, especially concerning phasic activity during REM sleep, presented data support the essential role of REM density for the assessment of sleep in depression. As a quick and easy manner to compute measurement, M-LEM is suggested as additional parameter for the assessment of phasic activity during REM sleep.