Towards quantitative cutoffs for insomnia: how current diagnostic criteria mischaracterize remission

ObjectiveAlthough sleep symptoms of insomnia can be quantified, none of the current diagnostic systems stipulate quantitative cutoffs for sleep-onset latency (SOL) or wake time after sleep onset (WASO). Diagnoses are based instead on idiographic patient reports of “difficulty” falling/staying asleep. Therefore, we examined whether remission of insomnia as per the diagnostic criteria results from a normalization of quantitative sleep disturbance, or if it is simply reflective of tolerance to sleep symptoms.MethodsThis study involved a yearlong prospective investigation of 649 adults (48.1 ± 11.6 years; 69.3% female) with DSM-5-based insomnia. Participants completed measures of sleep disturbance, perceived sleep-related distress, daytime sleepiness, functional impairment, and workplace productivity at baseline and follow-up one year later.ResultsA total of 271 participants no longer met the DSM-5-based insomnia criteria at follow-up. However, 66% of these remitters reported ≥31 min of SOL and/or WASO. Daytime impairment in this subgroup of remitters was no different from that among individuals who met the diagnostic criteria at both baseline and follow-up (ie, chronic insomniacs). By contrast, follow-up impairment was significantly lower (F = 12.3; P < 0.01) among remitters whose sleep disturbance returned below empirically derived quantitative cutoffs (both SOL and WASO <31 min) than in chronic insomniacs.ConclusionThis is the first study on the long-term course of insomnia based on the newly established DSM-5 criteria. A troubling implication of findings is that a majority of insomniacs stop meeting the diagnostic criteria despite continued sleep disturbance and impairment. “Remission” in these cases is attributable instead to tolerance of sleep symptoms. Incorporating quantitative criteria into current diagnoses may offer a more sensitive assay of treatment needs.     

Trajectories of sleep problems from adolescence to adulthood. Linking two population-based studies from Norway

Study objectiveThe aim of the study is to assess stability and predictors of insomnia and sleep duration from adolescence to early adulthood.MethodsA longitudinal sample of 1257 individuals from three age cohorts were assessed from linked population-based studies, the youth@hordaland study from 2012 (age 16–18) and the SHoT2018 study (age 22–25). Identical measures of insomnia symptoms and sleep duration were analysed.ResultsThe stability of insomnia was high from adolescence to young adulthood, 50% of those with insomnia symptoms in adolescence still had insomnia symptoms six years later (adjusted IRR = 2.01; (CI 95%; 1.5–2.44)). Short sleep duration was also stable, with 67.8% of the adolescents in the lowest sleep duration quartile still remaining in the lowest quartile six years later. The overall rate of insomnia symptoms, long wake after sleep onset (WASO), and oversleeping increased from adolescence to young adulthood. Also, we observed a reduction in sleep efficiency and later rise times. There was no significant change in sleep onset latency (SOL).ConclusionInsomnia symptoms and short sleep duration are prevalent during both adolescence and young adulthood. Considerable individual stability and a rising rate of insomnia symptoms were observed over time. These findings underscore the importance of early identification and timely interventions to prevent chronic sleep problems.     

The influence of placebo administration on the first- night effect in patients with insomnia disorder

ObjectiveWe aimed to investigate the effects of placebo on the first-night effect (FNE) in insomniacs.MethodsIn sum, 36 patients with insomnia disorder who met the DSM-5 criteria were enrolled in this study. Sixteen patients with insomnia disorder were given two days of placebo intervention (placebo-administration group, PL). Twenty patients with insomnia disorder (drug-free group, DF) were not given any interventions. All participants underwent two consecutive nights of polysomnographic (PSG) testing in the sleep laboratory. Sleep diaries were recorded during one week at home before the PSG nights and on two subsequent nights.ResultsThe results demonstrated that compared with the DF group, sleep onset latency (SOL), time in bed (TIB) and wake after sleep onset (WASO) significantly increased and sleep efficiency (SE) significantly decreased in the first sleep lab night in the PL group (all p < 0.05). Moreover, compared with the second night, significant differences were observed in lower self-reported total sleep time (TST) and more subjective WASO during the first night in the PL group (all p < 0.05). However, no significant difference was found in the duration and percentage of N1, N2, N3 and REM between the two groups.ConclusionIn patients with insomnia disorder, placebo administration may increase the occurrence of worse sleep without causing a change in the duration and percentage of N1, N2, N3 and REM on the first sleep lab night. In some cases, a placebo may not serve as treatment but may result in a nocebo effect.     

Sleep assessment in aging adults with type 2 diabetes: agreement between actigraphy and sleep diaries

ObjectiveActigraphy and sleep diaries have been widely used to evaluate various sleep parameters. However, their agreement in diabetes patients remains unclear. The objective of this study was to examine the agreement between sleep outcomes measured by actigraphy and sleep diaries in aging adults with type 2 diabetes (T2D).MethodsA convenience sample of 53 T2D adults (aged 50–76 years) were enrolled. Participants wore a wrist ActiGraph and filled out a daily sleep diary for eight days. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were obtained from the actigraphy and sleep diaries. Bland–Altman plots were conducted to examine the agreement between each sleep outcome.ResultsThe differences for TST and SE assessed by actigraphy and sleep diaries were 11.3 min (SD 65.3) and 0.2% (SD 10.5). Bland–Altman plots revealed wide limits of agreement between actigraphy- and diary-measured TST (95%CI: −139.3 min, 116.7 min) and SE (95%CI: −20.9%, 20.4%). Systematic biases were present for WASO and SOL: compared to actigraphy, sleep diaries underestimated WASO and overestimated SOL. As the SOL and WASO increased, the agreement became lower.ConclusionOverall, the agreement between actigraphy and sleep diaries is poor across all measures in aging adults with T2D patients. Findings from this study highlight the need for sleep researchers and clinicians to consider the method used for sleep assessment when developing interventions or interpreting study findings.     

A novel approach using actigraphy to quantify the level of disruption of sleep by in-home polysomnography: the MrOS Sleep Study: Sleep disruption by polysomnography

BackgroundThe “first-night effect” of polysomnography (PSG) has been previously studied; however, the ability to quantify the sleep disruption level has been confounded with the use of PSG on all nights. We used actigraphy to quantify disruption level and examined characteristics associated with disruption.MethodsTotally, 778 older men (76.2 ± 5.4 years) from a population-based study at six US centers underwent one night of in-home PSG. Actigraphy was performed on the PSG night and three subsequent nights. Actigraphically measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) from the PSG night and subsequent nights were compared. Linear regression models were used to examine the association of characteristics and sleep disruption.ResultsOn average, sleep on the PSG night was worse than the following night (p < 0.05, TST 21 ± 85 min less, SE 2.3 ± 11.3% less, WASO 4.9 ± 51.8 min more, SOL 6.6 ± 56.2 min more). Sleep on the PSG night was significantly worse than that two and three nights later. Characteristics associated with greater sleep disruption on the PSG night included older age, higher apnea–hypopnea index, worse neuromuscular function, and more depressive symptoms. Minorities and men with excessive daytime sleepiness slept somewhat better on the PSG night.ConclusionsAmong older men, there was sleep disruption on the PSG night, which may lead to sleep time underestimation. The increase of sleep on the night after the PSG suggests that data from the second monitoring may overestimate sleep.     

Quantitative association between nocturnal voiding frequency and objective sleep quality in the general elderly population: the HEIJO-KYO cohort

ObjectiveA significant association between nocturia and subjective sleep quality has previously been reported; however, the association between nocturia and objective sleep quality remains unclear. The purpose of this study was to evaluate the quantitative association between nocturnal voiding (NV) frequency and objective sleep quality in a large, general, elderly population.MethodsNocturnal voiding frequency, objective sleep quality, and subjective sleep quality were measured among 1086 community-based elderly individuals using actigraphy and the Pittsburgh Sleep Quality Index (PSQI) questionnaire.ResultsIn multivariate analyses adjusted for potential confounding factors (such as age, gender, body mass index, medication use, renal function, bedtime, rising time, daytime physical activity, endogenous melatonin levels, and bedroom light levels), increased NV frequency, ranging from zero, one, two, three or more voids, was significantly associated with poorer objective sleep quality, including lower sleep efficiency (SE) and longer wake after sleep onset (WASO) (mean SE, 86.3, 84.8, 83.6, and 81.2%, respectively; p for trend <0.001; mean WASO: 42.6, 49.0, 53.6, and 66.1 min, respectively; p for trend <0.001), but shorter sleep onset latency (SOL) (mean SOL, 3.0, 3.0, 2.8, and 2.8 log min, respectively; p for trend = 0.018). In addition, an increased NV frequency was significantly associated with poorer subjective sleep quality in a multivariate model (mean PSQI global score, 4.60, 4.86, 5.22, and 5.48, respectively; p for trend 0.012).ConclusionThe present study revealed a quantitative association between NV frequency and objective sleep quality in the general elderly population.     

Disrupted sleep maintenance is associated with altered circadian phase and phase angle in community-dwelling adults

ObjectiveWe aimed to compare the sleep onset, dim light melatonin onset (DLMO) and phase angle (PA) between sleep onset and DLMO of insomnia patients with those of controls, and to examine the difference in these parameters in relation to objective sleep quality.MethodsParticipants were recruited from three Public Health Centers in Korea. Actigraphy recordings were conducted for seven days. Five hourly saliva samples were obtained from three hours prior to sleep onset. A total of 48 controls and 64 insomnia patients were analyzed. Nocturnal sleep parameters, DLMO, and PA were compared between the controls and insomnia patients, and between the controls and patients with difficulty in maintaining sleep (DMS). These sleep and circadian parameters were compared among the subgroups divided by wake after sleep onset (WASO) amount.ResultsThere were no significant differences in sleep parameters between the control and insomnia groups, and between the controls and DMS subgroup. The sleep onset, DLMO, and PA of the insomnia group or those of DMS subgroup were not different from those of controls. There were significant differences in the sleep onset and DLMO (p < 0.05) among mild, moderate, and severe WASO groups. A regression analysis revealed the earlier DLMO and shorter PA predicted the severity of WASO (p < 0.0001) in total participants.ConclusionsInsomnia patients exhibited no difference in their sleep timing and melatonin rhythm compared to controls. However, these circadian parameters varied depending on the severity of WASO, and advanced melatonin phase and its shortened phase angle were associated with worsening of sleep maintenance.     

Subtypes of insomnia and the risk of chronic spinal pain: the HUNT study

ObjectiveTo examine the association between subtypes of insomnia and the risk of chronic spinal pain.MethodsThe study comprised 16,401 participants without chronic spinal pain at baseline who were followed for ∼11 years. People were categorized into ‘no insomnia symptoms’, ‘subthreshold insomnia’, and ‘insomnia’. Insomnia was defined according to the diagnostic classification system requiring both daytime and nighttime symptoms, and further categorized into subtypes based on nighttime symptoms (ie, sleep onset latency [SOL-insomnia], wake after sleep onset [WASO-insomnia], early morning awakening [EMA-insomnia], or combinations of these). Subthreshold insomnia comprised those with only daytime impairment or one or more nighttime symptoms. Chronic spinal pain was defined as pain in either ‘neck’, ‘low back’, or ‘upper back’, or a combination of these.ResultsIn multivariable regression analysis using people without insomnia as reference, people with subthreshold insomnia or insomnia had relative risks (RRs) of chronic spinal pain of 1.29 (95% confidence interval [CI] 1.21–1.38) and 1.50 (95% CI 1.34–1.68), respectively. The RRs for people with one nighttime symptom were 1.30 (95% CI 0.83–2.05) for WASO-insomnia, 1.32 (95% CI 1.06–1.65) for EMA-insomnia, and 1.70 (95% CI 1.32–2.18) for SOL-insomnia, respectively. Combinations of nighttime insomnia symptoms gave RRs from 1.45 (95% CI 1.08–1.94) for WASO + EMA-insomnia to 1.72 (95% CI 1.36–2.19) for all nighttime symptoms (SOL + WASO + EMA-insomnia).ConclusionsThese findings suggest that the risk of chronic spinal pain is highest among persons with insomnia subtypes characterized by sleep onset latency or among those having insomnia symptoms in all parts of the sleep period.     

Relationship between insomnia and pain in major depressive disorder: A sleep diary and actigraphy study

ObjectivesInsomnia and pain are frequent complaints during the course of a major depressive episode. We analyzed the association between insomnia and pain symptoms using subjective and objective sleep measures.MethodsThis is a prospective, naturalistic follow-up study in a university-based psychiatric unit. Ninety-one Chinese patients were enrolled during an acute episode of major depressive disorder (mean age = 48 years, 73 women); 82 of them were reassessed 3 months later using the same assessment on sleep, pain, depressive, and anxiety symptoms. Clinician-rated insomnia symptoms were obtained using the insomnia items of the Hamilton Rating Scale for Depression. Subjective sleep disturbances were assessed using the Insomnia Severity Index (ISI). Detailed sleep pattern was acquired using sleep diary and actigraphy. Pain intensity was evaluated using a verbal rating scale, a visual analog scale, and a multidimensional pain scale.ResultsCross-sectional analyses found that insomnia symptoms and quantitative sleep parameters were related to pain symptoms. The correlations between sleep and pain scores were more significant after 3 months of pharmacotherapy as compared to baseline. After controlling for the severity of anxiety and depression, the ISI total score and actigraphy-derived wake after sleep onset and total sleep time remained significant in predicting pain.ConclusionThis study supports specific role of subjective sleep disturbances and actigraphic measures in predicting pain symptoms in major depressive disorder. Further studies using a micro-longitudinal design are necessary to find out the causal relationship between sleep and pain in depressed patients.     

Intraindividual sleep variability and its association with insomnia identity and poor sleep

ObjectiveInsomnia identity refers to the conviction that one has insomnia, which can occur independently of poor sleep. Night-to-night variability in sleep (termed intraindividual variability [IIV]) may contribute to insomnia identity yet remain undetected via conventional mean analyses. This study compared sleep IIV across four subgroups: noncomplaining good sleepers (NG), complaining poor sleepers (CP), complaining good sleepers (CG), and noncomplaining poor sleepers (NP).MethodsThis study analyzed 14 days of sleep diary data from 723 adults. Participants were classified according to presence/absence of a sleep complaint and presence/absence of poor sleep. A 2 × 2 multivariate analysis of covariance (MANCOVA) was performed to explore differences on five measures of sleep IIV: intraindividual standard deviation in total sleep time (iSD TST), sleep onset latency (iSD SOL), wake after sleep onset (iSD WASO), number of nightly awakenings (iSD NWAK), and sleep efficiency (iSD SE).ResultsMANCOVA revealed significant main effects of poor sleep, sleep complaint, and their interaction on sleep IIV. Poor sleepers exhibited greater IIV across all sleep parameters compared to good sleepers. Similarly, individuals with a sleep complaint exhibited greater IIV compared to individuals with no complaint. The interaction revealed that iSD SOL was significantly greater among CP than NP, and iSD NWAK was significantly greater among CG than NG.ConclusionsGreater night-to-night variability in specific sleep parameters was present among complaining versus noncomplaining sleepers in good and poor sleep subgroups. These findings suggest certain aspects of sleep consistency may be salient for treatment-seeking individuals based on their quantitative sleep status.     

Efficacy of brief behavioral treatment for insomnia in older adults: examination of sleep,mood, and cognitive outcomes

ObjectiveThe aim of the present study was to examine the effects of a brief behavioral intervention for insomnia (BBTi) on sleep parameters, mood, and cognitive functioning in older adults.MethodsOlder adults (aged 65 years or more) underwent four weekly sessions of BBTi or self-monitoring control (SMC). Participants completed 14 days of sleep diaries and actigraphy measuring sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE), and sleep quality ratings at baseline, post-treatment, and three month follow-up. Participants also completed mood scales (Geriatric Depression Scale [GDS]; Beck Depression Inventory-II; and State Trait Anxiety Inventory) and neuropsychological testing (measuring global cognition, language, memory, attention and processing speed, and executive function) at the three timepoints.ResultsSignificant condition (BBTi vs. SMC) x time (baseline vs. post-treatment vs. follow-up) interactions revealed that BBTi improved relative to baseline in sleep diary-reported SOL, WASO, SE, and sleep quality, and these improvements were maintained at follow-up. SMC showed no change in these measures. A main effect of time showed that actigraphy-measured WASO improved from baseline for both BBTi and SMC at post-treatment. A main effect of time revealed that both BBTi and SMC patients endorsed fewer GDS symptoms relative to baseline at post-treatment and follow-up. We observed no change in performance on neuropsychological measures.ConclusionsA four-week BBTi is an efficacious intervention for reducing insomnia symptoms in older adults. BBTi does not selectively improve mood or cognitive functioning. Future work should examine effects of BBTi on physiological measures of sleep architecture and day-to-day cognition.Clinical Trial IdentiferNCT02967185.     

The role of actigraphy in the assessment of primary insomnia: a retrospective study

ObjectiveThe aim of our study was to evaluate quantitative actigraphic criteria obtained using the Actiwatch device (AW64; Cambridge Neurotechnology Ltd., Cambridge, UK) to differentiate participants with insomnia from normal sleepers.MethodsIn our retrospective study, we recovered 493 actigraphic records from two sleep measure databases of patients with insomnia (n = 151) and one of normal sleepers (n = 342). We considered the following actigraphic sleep parameters: time in bed (TIB), sleep-onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), sleep efficiency (SE), number of awakenings (NWAK), terminal wakefulness (TWAK), fragmentation index (FI), and mean motor activity (MA). We also considered two actigraphic circadian indexes: interdaily stability and intradaily variability. Using the Youden index, we calculated the quantitative actigraphic criteria that performed best for each actigraphic sleep parameter. Finally, we created receiver operating characteristic curves to test the accuracy of each criterion identified.ResultsAll sleep parameters except TST and TWAK differentiated the two groups of participants, allowing calculation of quantitative actigraphic criteria. There were no differences in the circadian indices.ConclusionsThe quantitative actigraphic criteria obtained in our study were not the same as those obtained previously with a different device, suggesting the need to adopt shared technical solutions for actigraphy.     

Sleep and cognitive performance: cross-sectional associations in the UK Biobank

ObjectiveThe relationship between insomnia symptoms and cognitive performance is unclear, particularly at the population level. We conducted the largest examination of this association to date through analysis of the UK Biobank, a large population-based sample of adults aged 40–69 years. We also sought to determine associations between cognitive performance and self-reported chronotype, sleep medication use and sleep duration.MethodsThis cross-sectional, population-based study involved 477,529 participants, comprising 133,314 patients with frequent insomnia symptoms (age: 57.4 ± 7.7 years; 62.1% female) and 344,215 controls without insomnia symptoms (age: 56.1 ± 8.2 years; 52.0% female). Cognitive performance was assessed by a touchscreen test battery probing reasoning, basic reaction time, numeric memory, visual memory, and prospective memory. Adjusted models included relevant demographic, clinical, and sleep variables.ResultsFrequent insomnia symptoms were associated with cognitive impairment in unadjusted models; however, these effects were reversed after full adjustment, leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without. Relative to intermediate chronotype, evening chronotype was associated with superior task performance, while morning chronotype was associated with the poorest performance. Sleep medication use and both long (>9 h) and short (<7 h) sleep durations were associated with impaired performance.ConclusionsOur results suggest that after adjustment for potential confounding variables, frequent insomnia symptoms may be associated with a small statistical advantage, which is unlikely to be clinically meaningful, on simple neurocognitive tasks. Further work is required to examine the mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance and the impairment associated with morning chronotype, sleep medication use, and sleep duration extremes.     

Validation of a multi-sensor activity monitor for assessing sleep in children and adolescents

ObjectiveTo assess the validity of a multi-sensor activity monitor in estimating sleep and wake compared to polysomnography in children and adolescents.MethodsA total of 43 children and adolescents (29 boys, 14 girls), aged 7–17 years (mean age [SD] = 11.0 [2.4] years) participated in the study. Participants wore the SenseWear Pro₃ Armband™ (SWA) body monitor (BodyMedia Inc) during an overnight polysomnographic assessment in a paediatric sleep laboratory. Sleep measures included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE).ResultsNo systematic bias of the SWA was noted for any of the sleep measures assessed, but limits of agreement were wide and amounted to −76 to +58 min for SOL, −75 to 102 min for WASO, −109 to +99 min for TST and −22 to +20% for SE. In addition, no effect of gender, age group (children versus adolescents) or overweight on the accuracy of the SWA was found.ConclusionsThe SenseWear Armband™ showed good agreement with polysomnography at the group level, while at the individual level rather, poor agreement between the two methods was observed. Consequently, at this point the use of the SWA in the clinical evaluation of sleep cannot be advocated.     

Actigraphy scoring for sleep outcome measures in chronic obstructive pulmonary disease

BackgroundActigraphy is commonly used to measure sleep outcomes so that sleep can be measured conveniently at home over multiple nights. Actigraphy has been validated in people with sleep disturbances; however, the validity of scoring settings in people with chronic medical illnesses such as chronic obstructive pulmonary disease remains unclear. The purpose of this secondary analysis was to compare actigraphy-customized scoring settings with polysomnography (PSG) for the measurement of sleep outcomes in people with chronic obstructive pulmonary disease who have insomnia.MethodsParticipants underwent overnight sleep assessment simultaneously by PSG and actigraphy at the University of Illinois of Chicago Sleep Science Center. Fifty participants (35 men and 15 women) with mild-to-severe chronic obstructive pulmonary disease and co-existing insomnia were included in the analysis. Sleep onset latency, total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE) were calculated independently from data derived from PSG and actigraphy. Actigraphy sleep outcome scores obtained at the default setting and several customized actigraphy settings were compared to the scored PSG results.ResultsAlthough no single setting was optimal for all sleep outcomes, the combination of 10 consecutive immobile minutes for sleep onset or end and an activity threshold of 10 worked well. Actigraphy overestimated TST and SE and underestimated WASO, but there was no difference in variance between PSG and actigraphy in TST and SE when the 10 × 10 combination was used. As the average TST and SE increased, the agreement between PSG and actigraphy appeared to increase, and as the average WASO decreased, the agreement between PSG and actigraphy appeared to increase.ConclusionResults support the conclusion that the default actigraphy settings may not be optimal for people with chronic obstructive pulmonary disease and co-existing insomnia.     

I'm tired and it hurts! Sleep quality and acute pain response in a chronic pain population

Objective/BackgroundThere are bidirectional links between sleep quality and pain, with recent research suggesting that sleep impairment more strongly predicts future pain than vice versa. Relatively few studies have examined the relationship between sleep quality and acute pain among chronic pain patients. The purpose of the current study is to investigate relationships among subjective sleep quality and behavioral and physiological responses to a cold pressor pain task (CPT) in chronic pain patients.Patients/methodsIn sum, 120 individuals with chronic pain were included. Participants completed a series of questionnaires followed by the CPT. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Physiological baseline state and stress response were assessed before and during the CPT using heart rate (HR), electromyography frontalis (EMGF), galvanic skin response conductance (GSR), and skin temperature (°C). Multiple linear regressions adjusting for opioid usage were performed.ResultsAfter adjusting for opioid use, PSQI global score explained significant variance in pain tolerance (B = −5.37, β = −0.23, p = 0.01), baseline GSR (B = −0.66, β = −0.24, p = 0.01), and HR change from baseline to CPT (B = 1.33, β = 0.25, p = 0.01).ConclusionsWorse perceived sleep quality was associated with lower pain tolerance, lower baseline GSR conductance, and greater HR change from baseline to CPT. These findings underscore the importance of accounting for opioid usage and psychological dimensions of pain in the relationship between sleep and acute pain response in chronic pain populations.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Sleep-wake misperception. A comprehensive analysis of a large sleep lab cohort

ObjectivesSleep-wake misperception has mainly been reported in insomnia patients. Conversely, the present study aimed to assess the prevalence and correlates of sleep-wake misperception in a large cohort of patients with various sleep-wake disorders, all diagnosed along the third version of the International Classification of Sleep Disorders.MethodsWe retrospectively included 2738 patients examined by polysomnography, who in addition estimated upon awakening their total sleep time, sleep onset latency and Wake after sleep onset (WASO). We computed subjective-objective mismatch by the formula (subjective – objective value)/objective value ×100; negative and positive values indicated under- and overestimation, respectively.ResultsIn the entire sample, the magnitude of under- and overestimation of total sleep time was similar, but varied significantly between diagnostic groups, with insomnia and insufficient sleep syndrome showing the most pronounced underestimation and REM parasomnia and circadian rhythm disorders showing the most pronounced overestimation of total sleep time. In all diagnostic categories, a majority tended to overestimate their sleep onset latency and to underestimate the amount of WASO. Younger age was independently correlated with underestimation of total sleep time and WASO, and with overestimation of sleep onset latency. Overestimation of sleep onset latency independently correlated to an increased latency to N3 sleep stage on polysomnography.ConclusionsWhile sleep-wake misperception is highly prevalent in all sleep-wake disorders, significant differences exist in magnitude of under- and overestimation between distinct diagnostic groups.     

Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial

ObjectiveEsmirtazapine (Org 50081), a medication that binds with high affinity to serotonin 5-HT_2A and histamine-1 receptors, was evaluated as a potential treatment for insomnia.MethodsAdults with primary insomnia were treated with esmirtazapine (3.0 or 4.5 mg) or placebo in this 6-week, double-blind, randomized, polysomnography (PSG) study. The end points included wake time after sleep onset (WASO) (primary), latency to persistent sleep, and total sleep time. Patient-reported parameters were also evaluated, including sleep quality and satisfaction with sleep duration. Residual daytime effects and rebound insomnia (sleep parameters during the single-blind placebo run-out week after treatment ended) were also assessed.ResultsOverall, 419 patients were randomized and 366 (87%) completed treatment. The median decrease in PSG WASO (double-blind average) was 20.5 min for placebo, and 52.0 min and 53.6 min for the 3.0- and 4.5-mg esmirtazapine groups, respectively (P < 0.0001 vs. placebo for both doses). Changes in the other PSG parameters and in all patient-reported parameters were also statistically significant with both doses versus placebo. Overall, 35–42% of esmirtazapine-treated patients had adverse events (AEs) versus 29% in the placebo group. AEs were mild or moderate in most esmirtazapine-treated patients. Furthermore, the incidence of AEs leading to discontinuation was low (<8%).ConclusionsSix weeks of treatment with esmirtazapine was associated with consistent improvements in objective and patient-reported parameters of sleep onset, maintenance, and duration. It was generally well tolerated, and residual daytime effects were minimal and no rebound insomnia was observed.     

A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.