Insomnia Items Research Articles

Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

Sleep Problems and Gambling Disorder: Cross-Sectional Relationships in a Young Cohort.

To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). Secondary analysis of previously published data from 152 young adults, aged 18-29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder.

Reduced coupling between global signal and cerebrospinal fluid inflow in patients with depressive disorder: A resting state functional MRI study

BackgroundDepressed patients often suffer from sleep disturbance, which has been recognized to be responsible for glymphatic dysfunction. The purpose of this study was to investigate the coupling strength of global blood‑oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics, which is a biomarker for glymphatic function, in depressed patients and to explore its potential relationship with sleep disturbance by using resting-state functional MRI. MethodsA total of 138 depressed patients (112 females, age: 34.70 ± 13.11 years) and 84 healthy controls (29 females, age: 36.6 ± 11.75 years) participated in this study. The gBOLD-CSF coupling strength was calculated to evaluate glymphatic function. Sleep disturbance was evaluated using the insomnia items (item 4 for insomnia-early, item 5 for insomnia-middle, and item 6 for insomnia-late) of The 17-item Hamilton Depression Rating Scale for depressed patients, which was correlated with the gBOLD-CSF coupling strength. ResultsThe depressed patients exhibited weaker gBOLD-CSF coupling relative to healthy controls (p = 0.022), possibly due to impairment of the glymphatic system. Moreover, the gBOLD-CSF coupling strength correlated with insomnia-middle (r = 0.097, p = 0.008) in depressed patients.LimitationsThis study is a cross-sectional study. ConclusionOur findings shed light on the pathophysiology of depression, indicating that cerebral waste clearance system deficits are correlated with poor sleep quality in depressed patients.

The Relationship between Insomnia and the Pathophysiology of Major Depressive Disorder: An Evaluation of a Broad Selection of Serum and Urine Biomarkers.

Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (N = 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR16) and insomnia severity (QIDS-SR16 insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (M = 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (M = 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD.

0057 Age at menopause and insomnia in a racially diverse cohort

Abstract Introduction Menopause is related to major hormonal, physical, and psychological changes for women, each of which could influence their sleep. However, sleep in women post-menopause may differ by race and ethnicity. We aimed to examine associations between age at menopause and insomnia symptoms among US women by race and ethnicity. Methods We utilized 2008-2012 data from the Health and Retirement Study, a nationally representative cohort of US adults age 50+, restricted to women with natural transition to menopause. Age at menopause was retrieved from baseline information (2008) and was used to categorized women into premature menopause (age≤40y), early menopause (age 41-45y), and normal menopause (age>45y). An insomnia composite score was constructed from 2010 and 2012 survey items that assessed insomnia symptoms (i.e., trouble falling asleep, nighttime awakenings, early morning awakenings, and feelings of nonrestorative sleep). Insomnia items that were reported as “most of the time” were considered positive and contributed to the composite score (range: 0-4). We estimated associations between age at menopause and insomnia symptoms using linear regression models and logistic regression models for continuous and binary outcomes, respectively. Models were stratified by White/non-White race and were adjusted for age, education, physical activity, parity, marital status, and survey year. Results Among 4,435 women, 338, 701, and 3,396 reported premature, early, and normal menopause, respectively. In White women, premature menopause was associated with a higher mean composite insomnia score than those who had normal menopause (b=0.20, p=0.03). However, this association was not seen in non-Whites. For individual insomnia survey items, premature menopause in White women was associated with greater odds of nonrestorative sleep (OR=1.98, 1.30-3.03) compared with normal menopause. In contrast, a premature menopause was not associated with nonrestorative sleep in non-Whites. Premature menopause was not associated with other individual insomnia symptoms for both groups. Conclusion Premature transition to menopause is associated with increased insomnia symptoms in White women. Among individual insomnia features, premature menopause had the greatest impact on nonrestorative sleep. Given the importance of sleep quality for various health outcomes, our findings highlight a need for more dedicated sleep assessments in women who experience premature menopause. Support (If Any)

The relationship between the HDRS insomnia items and polysomnographic (PSG) measures in individuals with treatment-resistant depression

The Hamilton Depression Rating Scale (HDRS), which includes several insomnia-related items, is potentially valuable in evaluating both depressive and sleep symptoms. However, the HDRS insomnia items have not been fully assessed by objective measures. This study compared the three HDRS insomnia items (Early, Middle, and Late) with the corresponding objective polysomnography (PSG) measures of Sleep Latency (SL), middle wakefulness, and late wakefulness. The study used HDRS and PSG data from 130 baseline nights, drawn from 80 participants enrolled in clinical trials for treatment-resistant depression (TRD). Mixed models evaluated the relationship between the HDRS and PSG, and primary analyses examined the Early, Middle, and Late Insomnia HDRS items and the PSG variables SL and Waking After Sleep Onset (WASO). To approximate the Middle and Late HDRS Insomnia items more closely, WASO was divided into WASO before 4:00 a.m. (waking between Sleep Onset and 0400 h) and WASO after 4:00 a.m. (waking between 0400 h and 0700 h). Secondary analyses included summed HDRS Global Insomnia score. HDRS Early and Late Insomnia items predicted objective PSG measures of early and late wakefulness. For Early Insomnia, each additional point in severity was associated with 61% [95%CI: 35%, 93%] longer SL. For Late Insomnia, each additional point was associated with a 35% [95% CI: 13%, 63%] increase in WASO after 4:00 a.m. Middle Insomnia was marginally related to WASO before 4:00 a.m. HDRS Early and Late Insomnia items may thus provide an index of wakefulness in TRD and help monitor treatment response when objective measures such as PSG are not feasible. Clinical trials identifierwww.clinicaltrials.gov (NCT01204918, NCT00054704, NCT00088699).

Network Analysis of Depressive Symptomatology in Elderly Patients with Major Depressive Disorder

Background: A novel psychopathological approach is the application of network analysis, as it is proposed that symptoms and their interconnections constitute a disease itself, rather than simply being components or outcome factors of disease. Objective: Using data from the Clinical Research Center for Depression (CRESCEND) Study, this study examined depressive symptoms in elderly patients with major depressive disorder using a network analysis approach. Methods: Among 135 elderly patients with major depressive disorder who were recruited from the CRESCEND study, we created a network based on individual items from the Hamilton Depression Rating Scale (HAMD), with the nodes being each item (symptom) and the edges being the strength of the association between the items (interconnection). By calculating measures of centrality of each of the nodes, we were able to determine which depressive symptoms were most central (influential) in the network. Results: The insight item was completely unconnected with other items and it was excluded in terms of network analysis. Thus, a network analysis of the 16 HAMD items estimated that the anxiety psychic item was the most central domain, followed by insomnia (middle of the night), depressive mood, and insomnia (early hours of the morning) items. On the contrary, the retardation item was the most poorly interconnected with the network. Conclusion: We suggest that our study contributes to the literature because we have found that anxiety, depressed mood, and insomnia are most central to the network, indicating that they are the most influential symptoms in major depression in elderly individuals.

Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

Psychometric Properties of the Concise Associated Symptom Tracking Scale and Validation of Clinical Utility in the EMBARC Study.

ObjectiveThe authors aimed to evaluate psychometric properties of the Concise Associated Symptom Tracking (CAST) Scale and validate the clinical utility of measuring irritability by updating and replicating a previously published outcome calculator from the Combining Medications to Enhance Depression Outcomes (CO‐MED) trial.MethodsParticipants were 292 adults from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study who had completed the CAST scale at baseline. The scale's five‐domain (irritability, anxiety, mania, insomnia, and panic) structure was evaluated with confirmatory factor analysis. Correlations with other clinical measures were used to confirm convergent and divergent validity. Logistic regression analyses from CO‐MED were used to estimate individual outcomes in EMBARC.ResultsCronbach's alpha for the CAST scale was 0.78. Model fit for the five‐domain structure was adequate (goodness of fit index=0.93, comparative fit index=0.92, root mean square error of approximation=0.06). Scores on irritability, anxiety, panic, insomnia, and mania were correlated with scores on the Anger Attack Questionnaire irritability item (rs=0.50), Hamilton Rating Scale for Depression anxiety subscale (rs=0.24), Mood and Anxiety Symptoms Questionnaire anxious arousal scale (rs=0.44), Quick Inventory of Depressive Symptomatology Self‐Report insomnia items (rs=0.38), and Altman Self‐Rating Mania Scale (rs=0.39), respectively. Individual outcomes of remission (area under the curve [AUC]=0.805) and no meaningful benefit (AUC=0.779) were predicted with high accuracy among EMBARC participants using their baseline and week 4 scores for depression and irritability and model estimates from CO‐MED.ConclusionsMeasuring irritability may help predict clinical course. The CAST scale is a valid measure of depression‐associated symptoms, including irritability.

0535 Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Sage-217 in Postpartum Depression

Abstract Introduction Postpartum depression (PPD) is a specifier of major depressive disorder (MDD) with peripartum onset. SAGE-217, an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, demonstrated improvements in depressive and anxiety symptoms versus placebo in a Phase 3 trial in PPD (NCT02978326; ROBIN) and a pivotal trial in MDD (NCT03000530). In PPD and MDD, insomnia symptoms are key diagnostic features, comorbid sleep disorders are frequent, and insomnia is a common residual symptom. Here we conducted post-hoc analyses to assess insomnia symptoms in the ROBIN trial. Methods Women (n=151) ages 18-45, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a Hamilton Rating Scale for Depression (HAM-D) total score ≥26, were randomized 1:1 to receive outpatient SAGE-217 30mg or placebo for two weeks, with 4 weeks follow-up. Change from baseline (CFB) in HAM-D score at Day 15 was the primary endpoint. Secondary endpoints included CFB in HAM-D at other time points and the Montgomery-Åsberg Depression Rating Scale (MADRS). Post-hoc analyses assessed HAM-D insomnia subscale (HAM-D-Ins) and MADRS individual insomnia item (MADRS-Ins) scores. HAM-D and MADRS measures were evaluated using a mixed-effects model for repeated measures. Safety and tolerability were assessed by adverse event (AE) reporting. Results SAGE-217 demonstrated statistically significant Day 15 CFB versus placebo in HAM-D (primary endpoint: -17.8 vs. -13.6, p=0.0028), MADRS (-22.1 vs. -17.6, p=0.0180), and associated insomnia sub-scales/items (difference SAGE-217 vs. placebo; HAM-D-Ins: -1.003, p=0.0038; MADRS-Ins: -0.773, p=0.0116). Significant CFB in insomnia sub-scales/items favoring SAGE-217 were observed by Day 3 (HAM-D-Ins: -0.841, p=0.0142; MADRS-Ins: -0.710, p=0.017) and at Day 45 (HAM-D-Ins: -0.730, p=0.0207; MADRS-Ins: -0.636, p=0.0221). Most common (≥5%) AEs were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Conclusion SAGE-217 demonstrated improvements in depression symptoms, including insomnia symptoms, and was generally well tolerated. Support This study was sponsored by Sage Therapeutics, Inc.

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice.

Insomnia is associated with suicide attempt in middle-aged and older adults with depression.

Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35). Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable. The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder. Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults.

A Longitudinal Twin Study of Insomnia Symptoms in Adults.

Twin modeling was used to conduct a genetically informative longitudinal analysis of insomnia symptoms in both sexes. Data from the Virginia Adult Twin Studies of Psychiatric and Substance Use Disorders (n = 7,500) were used. Past-month insomnia symptoms were assessed at two time points with the shortened version of the Symptom Checklist-90. A composite score for the insomnia items (trouble falling asleep, restless or disturbed sleep, early morning awakenings) was computed. Twin modeling on the composite score was conducted in OpenMx to decompose the phenotypic variance, to examine the longitudinal stability of etiologic influences on insomnia symptoms, and to test for sex differences. Insomnia symptoms were most commonly endorsed at a mild severity level (composite score mean = 2.24, standard deviation = 2.51). There was no evidence for sex effects in either of the univariate models, and insomnia symptoms were found to be modestly heritable (~25% at Time 1 and ~22% at Time 2). In the longitudinal measurement model, which accounts for error of measurement, the heritability for the latent factor of insomnia symptoms increased substantially, and demonstrated quantitative sex differences. The heritability of the latent insomnia factor was ~59% in females and ~38% in males. Genetic factors influence insomnia symptoms in adults, moreso for females than males, and these influences are largely stable over time. When taking into account measurement error, heritability estimates are substantial, but unique environmental factors continue to account for a large amount of variance in insomnia symptoms.

Clinical and sociodemographic correlates of severe insomnia in psychotropic drug-free, Asian outpatients with major depressive disorder

BackgroundLittle has been known regarding the correlates of severe insomnia in major depressive disorder (MDD). This post-hoc analysis aimed to examine the sociodemographic and clinical correlates of severe insomnia in psychotropic drug-free, Asian adult outpatients with MDD. MethodsParticipants were psychotropic drug-free patients with MDD, aged 18–65 years. By using the Symptom Checklist-90 Items, Revised (SCL-90-R), a score of 4 (severe distress) on any one of three insomnia items was defined as severe insomnia. Other measures included the Montgomery–Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the nine psychopathology subscales of SCL-90-R, the Physical and Mental Component Summaries of Short Form Health Survey (SF-36 PCS and SF-36 MCS), and the Sheehan Disability Scale (SDS). ResultsOf 528 participants, their mean age being 39.5 (SD=13.26) years, 64.2% were females, and 239 (45.3%) had severe insomnia. The logistic regression model revealed that low educational qualifications (less than secondary school completion), high SCL-90-R Depression scores, high SCL-90-R Anxiety scores, and low SF-36 PCS scores were independently correlated with severe insomnia (p's<.05). LimitationsInsomnia was determined only by the patient's distress. Middle insomnia was not assessed. Psychotropic drug-free patients with MDD are not commonly seen in psychiatric practice. ConclusionSevere insomnia is common in patients with MDD. It is closely related with low educational qualification, subjective depression and anxiety severity, and poor physical health. These findings may implicate the treatment of comorbid MDD and severe insomnia, for example, sleep hygiene education, pharmacological treatment.

Abstract P5-17-02: Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC

Abstract Introduction: Eribulin mesylate is a nontaxane microtubule inhibitor approved to treat MBC in patients (pts) who previously received ≥2 chemotherapeutic regimens for MBC. A phase 2 study of first-line eribulin for HER2-negative (HER2-) MBC showed an overall response rate of 29%, median 6.8 m progression-free survival, and tolerability consistent with earlier studies. We present prespecified quality of life (QoL) results for this trial. Methods: Pts (N=56) received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-wk cycle (median: 7 cycles). QoL was assessed using the EORTC QoL assessment (QLQ-C30) and a breast-cancer specific questionnaire (QLQ-BR23) pretreatment (baseline) and on day 1 of every other cycle during treatment. Percentage of pts with at least ±10-point change from baseline was summarized descriptively. Linear mixed-effects models were used to evaluate changes over time and compare responders vs nonresponders controlling for baseline score and time effect. Time-to-event analysis was performed on time to deterioration, defined as time from 1st dose to 1st occurrence of worsening in QoL score that reached minimally clinically important difference (MID; eg, 10 points in global health status in QLQ-C30) from baseline without further improvement of at least MID. Results: For QLQ-C30 at cycle 6 (n=29), more pts had at least a 10-point improvement from baseline in role, emotional, and social functioning; fatigue, nausea/vomiting, pain, dyspnea, and insomnia item scores, than had worsening. More pts had worsening in global health status/QoL, cognitive functioning, and diarrhea (Table). Category, n (%) ImprovedStableWorsenedGlobal health status/QoL2 (7)16 (55)11 (38)Physical functioning9 (31)13 (45)7 (24)Role functioning14 (48)10 (35)5 (17)Emotional functioning9 (31)14 (48)6 (21)Cognitive functioning2 (7)13 (45)14 (48)Social functioning10 (35)13 (45)6 (21)Fatigue16 (55)5 (17)8 (28)Nausea and vomiting8 (28)16 (55)5 (17)Pain15 (52)8 (28)6 (21)Dyspnea9 (31)18 (62)2 (7)Insomnia12 (41)15 (52)2 (7)Appetite loss7 (24)16 (55)6 (21)Constipation5 (17)18 (62)6 (21)Diarrhea2 (7)21 (72)6 (21) Median time to deterioration in global health status/QoL was 5.06 m (responders, 8.54 m; nonresponders, 3.71 m; hazard ratio=0.60, P=0.22). In linear mixed models, responders (n=16) performed better than nonresponders (n=40) in role functioning (P=0.011), emotional functioning (P=0.031), fatigue (P=0.007), pain (P=0.047), insomnia (P=0.018), and appetite loss (P=0.032). Mean symptom scores were significantly correlated with corresponding adverse event rates for nausea and vomiting, dyspnea, appetite loss, constipation, and diarrhea; Spearman rank correlation coefficients ranged from 0.31 to 0.54. For QLQ-BR23 at cycle 6, symptom scores were mostly stable; more pts had worsening in body image and systemic therapy side effects than had improvement and more pts had improvement in breast and arm symptoms than had worsening. Responders also had longer time to symptom deterioration. Conclusions: In this study of first-line eribulin treatment for HER2- MBC, a majority of pts had stable or improvement in QoL scales. Responders to eribulin were more likely than nonresponders to have stable or improved QoL. Citation Format: Lee Schwartzberg, Kristi McIntyre, Joyce O'Shaughnessy, Stefan Glück, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-02.

Various types of sleep disturbance due to different sorts of low back pain. A literature review: 2. A single insomnia severity measure and multiple insomnia items

Aim This is the second part of a literature review series and a data analysis study, which seek to find out whether different types of sleep disturbance can be caused by different sorts of back pain. Here in Part 2, we examine how the single item sleep question acts as a severity measure of back pain for statistical purposes. Conversely, there are multiple subdivisions, items, or factors that are distinctive each in their own right, and may each have clinical meaning. Methods The same search of Medline, Embase, PsycINFO, and the OVID journals databases using the keywords ‘low back pain’ and ‘sleep’ used for the initial part of the review process was again the basis for this part of the literature review. Results The manner in which ancient languages and modern English describe aspects of sleep, insomnia, fatigue, and tiredness has evolved over time was felt to be worth examination. Then the single and multiple item views of insomnia studied in questionnaire-based research were inspected. This was in part ...

EPA-1075 – Initial insomnia and cortisol levels in depressed adolescents

Introduction Many studies have observed hyperactivity of the hypothalamic-pituitary-adrenal axis in depression. In general, cortisol levels are tend to be lower in the evenings and exogenous corticosteroids administered around this time are known to cause insomnia. Objectives We planned to compare data on evening cortisol levels in subjects with initial insomnia versus those without initial insomnia. We also used peak morning cortisol levels to establish the specificity of our effect. Aims To test the hypothesis that high evening cortisol is associated with initial insomnia among depressed adolescents. Methods Data from the baseline results of the Improving Mood with Psychoanalytic And Cognitive Therapies (IMPACT) trial were used. There were 471 depressed subjects aged 11–17. Saliva was collected at waking, waking plus 30 minutes and late evening on two consecutive days for cortisol assay. Insomnia was defined as present or absent based on the insomnia item of the K-SADS-PL. Non-parametric analysis was used due to nonnormal data. Results Median evening cortisol for subjects with initial insomnia was 0.070μg/dl, whereas it was 0.050μg/dl for those without initial insomnia (n=151, Mann-Whitney z = 2.33, p=.02). In contrast, there was no statistically significant difference in morning cortisol levels between the two groups (n=151, p=.93). Conclusions As hypothesised, high evening cortisol was associated with initial insomnia. It is possible, therefore, that high evening cortisol drives insomnia among a sub-population of depressed adolescents. However, interpreting the direction of causality is difficult, as sleep deprivation has also been shown to cause high evening cortisol.

Relationship among nightmare, insomnia and depression among residents in Japanese rural community

Introduction Either nightmare or insomnia is known as independent factor associated with aggravation of depression. The aim of this community-based study was to clarify the relationship between the impacts of nightmare and insomnia on depressive status. Materials and methods This cross-sectional survey was conducted on residents in a rural community of Japan. A total of 2822 persons were eligible for this questionnaire survey including demographic variables, sleep hygiene related variables, the Pittsburgh Sleep Quality Index (PSQI) assessing the severity of insomnia, and a 12-item version of the Center for Epidemiological studies Depression scale (CES-D) manifesting the severity of depression. The frequency of nightmare was assessed with an item of nightmare on the PSQI. The total score of CES-D after excluding the insomnia item was used as the score of depression and that of PSQI after excluding the nightmare item was used as the score of insomnia. Results The result of multiple regression analysis revealed that both nightmare score and insomnia score were significantly associated with CES-D score (adjusted R2=0.18, p f A=0.09, p f A=0.39, p p fÅ 2=0.12). Post-hoc analysis revealed that the group with coexistence of nightmare and insomnia had significantly higher score than the healthy group ( p p p p p Conclusion Coexistence of nightmare and insomnia was thought to synergistically aggravate depressive symptom. Moreover, both nightmare and insomnia was thought to become a risk factor for the depression independently in the Japanese rural population. Acknowledgements We thank Kiyohisa Takahashi(Japan Foundation for Neuroscience and Mental Health) for helpful comments on the manuscript.

Insomnia, Quality Of Life and MPN Symptom Burden: An Analysis By The MPN Quality Of Life International Study Group (MPN-QOL ISG)

BackgroundWe have previously reported on the high prevalence and severity of insomnia amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between insomnia and the MPN disease features (in particular splenomegaly, status of blood counts), individual MPN symptom prevalence and severity, language, and overall quality of life. MethodsData was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF insomnia item asked about “difficulty sleeping”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF insomnia item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the insomnia item with the final multivariate model selected using forward regression. ResultsDemographics A total of 1992 MPN patients (essential thrombocythemia=834, polycythemia vera=703, myelofibrosis=449, unknown=6) completed the insomnia item. Participants were of typical age (median=61, range-15-94) and gender (female=54%). Overall, 1307 subjects endorsed the MPN insomnia item (score >0) with an overall mean symptom score of 3.0 (median=2.0, SD=3.1. range=0-10); 603/1992 (30%) of patients had severe insomnia related complaints (score >4). Univariate AnalysisAmong QLQ-C30 functioning scales, emotional functioning most highly correlated with the MPN-SAF insomnia item (r=-.47, p<0.001) with all other domains also having statistically significant but slightly weaker correlation (all p<0.001). Among QLQ-C30 symptom scales, insomnia (r=.79, p<0.001) and fatigue (r=.45, p<0.001) most highly correlated with the MPN-SAF insomnia item with all other QLQ-C30 symptoms having correlations between .13 and .37 (all p<.001). Among MPN-SAF items, the MPN-SAF insomnia item correlated with all MPN-SAF items (all p<0.001) including the TSS (r=0.55, p<0.001) and most highly with depression (r=.52, p<0.001), concentration problems (r=.43, p<0.001), overall QOL (r=.41, p<0.001), night sweats (r=.41, p<0.001), and extremity tingling (r=.40, p<0.001). MPN-SAF insomnia significantly differed by gender (means: M 2.4, F 3.4; p<0.001), language (means ranged from 2.6 [Italian] to 3.6 [German]; p=0.01), anemia (means: absent 2.8, present 3.5; p<0.001), prior hemorrhage (means: no 2.9, yes 3.7; p=0.01), and requiring red blood cell transfusion (means: no 2.9, yes 3.6; p=0.03), with a trend for a difference by MPN type (ET mean=2.7, PV mean=3.0, MF mean=3.2; p=0.06). Multivariate AnalysisIn a multivariate model of MPN-SAF insomnia containing all QLQ-C30 functioning scales, physical, emotional, and cognitive functioning along with global health status/QOL were all significant (all p<0.001). Numerous symptoms were also significant in a multivariate model of MPN-SAF insomnia containing all other MPN-SAF symptoms (all p<0.05: headaches, extremity tingling, depression, sexual problems, night sweats, pruritus, fever, and QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, gender, QLQ-C30 emotional functioning and MPN-SAF items to be significant. ConclusionsInsomnia is highly prevalent and severe in MPN patients and closely correlates with most other MPN-related symptoms and functional domains bearing a multi-faceted impact on overall quality of life. Correlations between insomnia and emotional, cognitive, and physical complaints including depression/sad mood, concentration problems, night sweats, and numbness/tingling in the extremities suggest that the cause of MPN-related sleep complaints is likely complex. Future studies should evaluate the impact of interventions on MPN associated insomnia as well as its biological underpinnings. Disclosures:Etienne:novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

Change in sleep symptoms across Cognitive Processing Therapy and Prolonged Exposure: A longitudinal perspective

Sleep disturbance is a core component in posttraumatic stress disorder (PTSD). Although cognitive-behavioral treatments for PTSD reduce the severity of sleep symptoms, they do not lead to complete remission. The present study examines the impact of Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) on subjective measures of sleep disturbance from treatment randomization through long-term follow-up (LTFU). Participants were 171 female rape victims with PTSD who were randomly assigned to CPT, PE, or Minimal Attention (MA). After 6-weeks, the MA group was randomized to CPT or PE. Sleep symptoms were assessed at baseline, post-MA, post-treatment, 3-months, 9-months and LTFU using the Pittsburgh Sleep Quality Index (PSQI) and nightmare and insomnia items from the Clinician Administered PTSD Scale. Change in sleep during MA, from pre- to post-treatment for CPT and PE, and from post-treatment through LTFU was assessed using piecewise hierarchical linear modeling with the intent-to-treat sample. Controlling for medication, sleep improved during CPT and PE compared to MA, and treatment gains were maintained through LTFU. CPT and PE were equally efficacious and improvements persist over LTFU, yet, neither produced remission of sleep disturbance. Overall, sleep symptoms do not remit and may warrant sleep-specific treatments.