Elevated estradiol during a hormone simulated pseudopregnancy decreases sleep and increases hypothalamic activation in female Syrian hamsters.

Sleep disruptions are a common occurrence during the peripartum period. While physical and environmental factors associated with pregnancy and newborn care account for some sleep disruptions, there is evidence that peripartum fluctuations in estrogens may independently impact sleep. However, the impact of these large fluctuations in estrogens on peripartum sleep is unclear because it is difficult to tease apart the effects of estrogens on sleep from effects associated with the growth and development of the fetus or parental care. We therefore used a hormone-simulated pseudopregnancy (HSP) in female Syrian hamsters to test the hypothesis that pregnancy-like increases in estradiol decrease sleep in the absence of other factors. Adult female Syrian hamsters were ovariectomized and given daily hormone injections that simulate estradiol levels during early pregnancy, late pregnancy, and the postpartum period. Home cage video recordings were captured at seven timepoints and videos were analyzed for actigraphy. During "late pregnancy," total sleep time and sleep efficiency were decreased in hormone-treated animals during the white light period compared to pretest levels. Likewise, during "late pregnancy," locomotion was increased in the white light period for hormone-treated animals compared to pretest levels. These changes continued into the "postpartum period" for animals who continued to receive estradiol treatment, but not for animals who were withdrawn from estradiol. At the conclusion of the experiment, animals were euthanized and cFos expression was quantified in the ventral lateral preoptic area (VLPO) and lateral hypothalamus (LH). Animals who continued to receive high levels of estradiol during the "postpartum" period had significantly more cFos in the VLPO and LH than animals who were withdrawn from hormones or vehicle controls. Together, these data suggest that increased levels of estradiol during pregnancy are associated with sleep suppression, which may be mediated by increased activation of hypothalamic nuclei.

Association Between Pretreatment Sleep Disturbance and Radiation Therapy-Induced Pain in 573 Women With Breast Cancer.

CONTEXT: Pain can be a debilitating side effect of radiation therapy (RT). Data from the general population have shown that sleep disturbance can influence pain incidence and severity; however, less is known about this relationship in patients with breast cancer receiving RT. OBJECTIVES: This secondary analysis examined the association of pretreatment moderate/severe levels of sleep disturbance with subsequent RT-induced pain after adjusting for pre-RT pain. METHODS: We report on 573 female patients with breast cancer undergoing RT from a previously completed Phase II clinical trial for radiation dermatitis. Sleep disturbance, total pain, and pain subdomains-sensory pain, affective pain, and perceived pain intensity were assessed at pre-RT and post-RT. At pre-RT, patients were dichotomized into two groups: those with moderate/severe sleep disturbance (N = 85) vs. those with no/mild sleep disturbance (control; N = 488). RESULTS: At pre-RT, women with moderate/severe sleep disturbance were younger, less likely to be married, more likely to have had mastectomy and chemotherapy, and more likely to have depression/anxiety disorder and fatigue than the control group (all Ps < 0.05). Generalized estimating equations model, after controlling for pre-RT pain and other covariates (e.g., trial treatment condition and covariates that were significantly correlated with post-RT pain), showed that women with moderate/severe sleep disturbance at pre-RT vs. control group had significantly higher mean post-RT total pain as well as sensory, affective, and perceived pain (effect size = 0.62, 0.60, 0.69, and 0.52, respectively; all Ps < 0.05). CONCLUSION: These findings suggest that moderate/severe disturbed sleep before RT is associated with increased pain from pre-to-post-RT in patients with breast cancer.

Cognitive Behavioral Therapy for Insomnia Reduces Depression in Cancer Survivors.

STUDY OBJECTIVES: The current archival analyses examine the direct and indirect effects of cognitive behavioral therapy for insomnia (CBT-I) on depression in cancer survivors. METHODS: We report on 67 cancer survivors from a 2 × 2 randomized controlled trial of CBT-I and armodafinil for insomnia, after collapsing across the noneffective study medication conditions (armodafinil/placebo) to create CBT-I (yes/no). Depression and insomnia were assessed before, during the 7-week CBT-I intervention, at postintervention, and 3 months later by the Patient Health Questionnaire and the Insomnia Severity Index, respectively. RESULTS: Mean depression at baseline for all participants was 6.44 (standard error = 0.41, range 0-15). Paired t tests showed that depression improved from baseline to postintervention by 48% (P < .001) in the CBT-I group versus 15% (P = .016) in the non-CBT-I group. Analysis of covariance controlling for baseline found that participants receiving CBT-I had significantly less depression at postintervention (effect size = -0.62; P = .001), compared to those who did not receive CBT-I. These benefits were maintained at the 3-month follow-up. Spearman rank correlations showed that changes in insomnia severity from baseline to postintervention were significantly correlated with concurrent changes in depression (r = .73; P < .001). Path analysis revealed that improvement in depression was mediated by improvement in insomnia severity (P < .001). CONCLUSIONS: Our findings provide preliminary support that in cancer survivors, CBT-I reduces depression via improvement in insomnia. Further, this reduction in depression remained stable 3 months after completing CBT-I. This suggests that a CBT-I intervention has a meaningful effect on depression. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Cognitive Behavioral Therapy +/- Armodafinil for Insomnia and Fatigue Following Chemotherapy; Identifier: NCT01091974; URL: https://clinicaltrials.gov/ct2/show/record/NCT01091974.

Social Support, Insomnia, and Adherence to Cognitive Behavioral Therapy for Insomnia After Cancer Treatment.

OBJECTIVE/BACKGROUND: While cognitive-behavioral therapy for insomnia (CBT-I) has been shown to be efficacious in treating cancer survivors' insomnia, 30-60% of individuals have difficulty adhering to intervention components. Psychosocial predictors of adherence and response to CBT-I, such as social support, have not been examined in intervention studies for cancer survivors. PARTICIPANTS: Data from a randomized placebo-controlled 2 x 2 trial of CBT-I and armodafinil (a wakefulness promoting agent) were used to assess adherence. Ninety-six cancer survivors participated in the trial (mean age 56, 86% female, 68% breast cancer). METHODS: CBT-I and armodafinil were administered over the course of seven weeks, and participants were assessed at baseline, during intervention, postintervention, and at a three-month follow-up. Social support was assessed using a Functional Assessment of Chronic Illness Therapy subscale, insomnia severity was assessed using the Insomnia Severity Index, and adherence was measured based on CBT-I sleep prescriptions. RESULTS: At baseline, social support was negatively correlated with insomnia severity (r = -0.30, p = 0.002) and associations between social support, CBT-I, and insomnia were maintained through the three-month follow-up. Social support was positively associated with adherence to CBT-I during intervention weeks 3, 4, and 5, and with overall intervention adherence. At postintervention, both social support and treatment with CBT-I independently predicted decreased insomnia severity (p < 0.01) when controlling for baseline insomnia severity. CONCLUSIONS: Higher social support is associated with better intervention adherence and improved sleep independent of CBT-I. Additional research is needed to determine whether social support can be leveraged to improve adherence and response to CBT-I.

Are sleep continuity disturbance and fatigue prodromal symptoms of cancer development?

Sleep continuity disturbance (also known as insomnia) and fatigue are common complaints of individuals diagnosed with cancer. Traditionally, many have believed that sleep continuity disturbance and fatigue are caused, in large measure, by the impact of the cancer diagnosis and treatment. Recent prospective research suggests however, that sleep continuity disturbance and fatigue may actually precede a cancer diagnosis. We suggest that sleep continuity disturbance and fatigue may in fact represent prodromal symptoms of cancer. We review the current perspectives of this sequence of events and present a revised schematic that accounts for the role of biological, behavioural, and cognitive factors that contribute to the development and maintenance of sleep continuity disturbances in cancer patients. Monitoring emergent and unexplained patient-reported fatigue, sleepiness, and insomnia may serve as early warning signs of new onset cancer, providing opportunity for early detection and early intervention.

Effects of cognitive behavioral therapy for insomnia and armodafinil on quality of life in cancer survivors: a randomized placebo-controlled trial.

PURPOSE: Cancer-related insomnia is associated with diminished quality of life (QOL), suggesting that improvement in insomnia may improve QOL in cancer survivors. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia, but less is known regarding its effect on QOL and whether improvement in insomnia corresponds to improved QOL. The present analysis examines the effects of CBT-I, with and without armodafinil, on QOL both directly and indirectly through improvements of insomnia. METHODS: This is an analysis of 95 cancer survivors for a specified secondary aim of a four-arm randomized controlled trial assessing the combined and individual effects of CBT-I and armodafinil to improve insomnia. QOL and insomnia severity were assessed before, during the intervention, at post-intervention, and 3 months later by Functional Assessment of Cancer Therapy-General and Insomnia Severity Index, respectively. RESULTS: Mean change in QOL from pre- to post-intervention for CBT-I + placebo, CBT-I + armodafinil, armodafinil, and placebo was 9.6 (SE = 1.8; p < 0.0001), 11.6 (SE = 1.8; p < 0.0001), -0.2 (SE = 3.2; p = 0.964), and 3.3 (SE = 2.0; p = 0.124), respectively. ANCOVA controlling for pre-intervention scores showed that participants receiving CBT-I had significantly improved QOL at post-intervention compared to those not receiving CBT-I (p < 0.0001, effect size = 0.57), with benefits being maintained at the 3-month follow-up. Path analysis revealed that this improvement in QOL was due to improvement in insomnia severity (p = 0.002), and Pearson correlations showed that changes in QOL from pre- to post-intervention were significantly associated with concurrent changes in insomnia severity (r = -0.56; p < 0.0001). Armodafinil had no effect on QOL for those who did or did not receive it (p = 0.976; effect size = -0.004). CONCLUSION: In cancer survivors with insomnia, CBT-I resulted in clinically significant improvement in QOL via improvement in insomnia. This improvement in QOL remained stable even 3 months after completing CBT-I. IMPLICATIONS FOR CANCER SURVIVORS: Considering the high prevalence of insomnia and its detrimental impact on QOL in cancer survivors and the effectiveness of CBT-I in alleviating insomnia, it is important that evidence-based non-pharmacological sleep interventions such as CBT-I be provided as an integral part of cancer care.

Questionnaires that screen for multiple sleep disorders.

The goal of this review was to identify, describe, and evaluate the existing multiple sleep disorders screening questionnaires for their comprehensiveness, brevity, and psychometric quality. A systematic review was conducted using Medline/PubMed, cumulative index to nursing & allied health literature, health and psychosocial instruments and the "grey literature". Search terms were "sleep disorders, screening, questionnaires, and psychometrics". The scope of the search was limited to English language articles for adult age groups from 1989 through 2015. Of the n = 2812 articles identified, most were assessment or treatment guideline reviews, topical reviews, and/or empirical articles. Seven of the articles described multiple sleep disorders screening instruments. Of the identified instruments, two questionnaires (the Holland sleep Disorders questionnaire and sleep-50) were evaluated as comprehensive and one questionnaire (the global sleep assessment questionnaire [GSAQ]) was judged to be both comprehensive and efficient. The GSAQ was found to cover four of the six core intrinsic disorders, sleep insufficiency, and daytime sequela with 11 questions. Accordingly, the GSAQ is the most suitable for application as a general sleep disorders screener. Additional work is required to validate this instrument in the context of primary care. Finally, the future development of multiple sleep disorders screening questionnaires should not only cover all six intrinsic sleep disorders but also acquire some basic demographic information (age, sex, body mass index, presence/absence of bed partner, work status and shift) and some limited data regarding sleep sufficiency and the daytime consequences of sleep disturbance.

Effects of armodafinil and cognitive behavior therapy for insomnia on sleep continuity and daytime sleepiness in cancer survivors.

STUDY OBJECTIVES: This study involves the analysis of a secondary outcome of a trial examining whether cognitive behavior therapy for insomnia (CBT-I), a wake-promoting medication (armodafinil), or both results in greater improvement in prospectively assessed sleep continuity and daytime sleepiness than a placebo-alone group among a heterogeneous group of cancer survivors. Whether or not armodafinil alone, and/or when combined with CBT-I, affected adherence with CBT-I was evaluated. DESIGN: This study is a randomized, placebo-controlled, clinical trial. SETTING: This study was conducted at two northeastern academic medical centers. PARTICIPANTS: Eighty-eight cancer survivors with chronic insomnia were recruited between October 2008 and November 2012. Participants were assigned to one of four conditions: 1) CBT-I and placebo (CBT-I+P); 2) CBT-I and armodafinil (CBT-I + A); 2) armodafinil alone (ARM); or 4) placebo alone (PLA). INTERVENTIONS: CBT-I was delivered in seven weekly individual therapy sessions (three in person, four via telephone). The armodafinil dosage was 50 mg BID. MEASUREMENTS AND RESULTS: Sleep continuity was measured with daily sleep diaries assessing sleep latency (SL), wake after sleep onset (WASO), and total sleep time (TST). The Epworth Sleepiness Scale (ESS) measured daytime sleepiness. Compared to the PLA group, the CBT-I+P and CBT-I+A groups reported a significant reduction in SL with effect sizes of 0.67 and 0.58, respectively. A significant reduction was observed in WASO in the CBT-I+A group with an effect size of 0.64. An increasing trend of TST was observed in the CBT-I+P, CBT-I+A, and PLA groups, but not in the ARM group. No statistically significant reductions in daytime sleepiness (ESS) were observed for any of the groups. CONCLUSION: CBT-I alone and in combination with armodafinil caused significant improvement in sleep continuity. The addition of armodafinil did not appear to improve daytime sleepiness or enhance adherence to CBT-I.

Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial.

PURPOSE: Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors. Herein, we examine the effect of CBT-I, with and without A, on fatigue in cancer survivors. PATIENTS AND METHODS: This study was a four-arm factorial study with CBTI-I (yes/no) versus A (yes/no). It consisted of 96 cancer survivors (average age 56 years; 88 % female; 68 % breast cancer). Fatigue was assessed by the brief fatigue inventory (BFI) and the FACIT-Fatigue scale. The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A. RESULTS: Analyses adjusting for baseline differences showed that CBT-I improved fatigue as measured by two separate scales (BFI: P = 0.002, Std. error = 0.32, effect size (ES) = 0.46; FACIT-Fatigue: P < 0.001, Std. error = 1.74, ES = 0.64). Armodafinil alone did not show a statistically significant effect on fatigue levels (all Ps > 0.40) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue. CONCLUSIONS: CBT-I with and without armodafinil resulted in a clinically and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia. Armodafinil did not improve cancer-related fatigue (CRF) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and, if indicated, treated for insomnia as part of a comprehensive fatigue management program.

Randomized placebo-controlled trial of cognitive behavioral therapy and armodafinil for insomnia after cancer treatment.

PURPOSE: Insomnia is a distressing and often persisting consequence of cancer. Although cognitive behavioral therapy for insomnia (CBT-I) is the treatment of choice in the general population, the use of CBT-I in patients with cancer is complicated, because it can result in transient but substantial increases in daytime sleepiness. In this study, we evaluated whether CBT-I, in combination with the wakefulness-promoting agent armodafinil (A), results in better insomnia treatment outcomes in cancer survivors than CBT-I alone. PATIENTS AND METHODS: We report on a randomized trial of 96 cancer survivors (mean age, 56 years; female, 87.5%; breast cancer, 68%). The primary analyses examined whether ≥ one of the 7-week intervention conditions (ie, CBT-I, A, or both), when compared with a placebo capsule (P) group, produced significantly greater clinical gains. Insomnia was assessed by the Insomnia Severity Index and sleep quality by the Pittsburgh Sleep Quality Inventory. All patients received sleep hygiene instructions. RESULTS: Analyses controlling for baseline differences showed that both the CBT-I plus A (P = .001) and CBT-I plus P (P = .010) groups had significantly greater reductions in insomnia severity postintervention than the P group, with effect sizes of 1.31 and 1.02, respectively. Similar improvements were seen for sleep quality. Gains on both measures persisted 3 months later. CBT-I plus A was not significantly different from CBT-I plus P (P = .421), and A alone was not significantly different from P alone (P = .584). CONCLUSION: CBT-I results in significant and durable improvements in insomnia and sleep quality. A did not significantly improve the efficacy of CBT-I or independently affect insomnia or sleep quality.

Suicidal ideation in veterans misusing alcohol: relationships with insomnia symptoms and sleep duration.

OBJECTIVE: The aim of this investigation was to assess the relationships between suicidal ideation and insomnia symptoms in Veterans misusing alcohol. METHOD: Data were extracted in this retrospective chart review of Veterans referred from primary care for a behavioral health evaluation (N=161) based on evidence of heavy drinking, drug use or another behavioral problem. Suicidal ideation (SI) was assessed using the Paykel questionnaire. Insomnia symptoms were assessed with standard diary questions in an interview format and pertained to sleep latency (SL), wake after sleep onset time (WASO), sleep quality (SQ), and habitual sleep duration (HSD). The relations between suicidal ideation and insomnia symptoms were assessed using ordinal regression analyses adjusted for socio-demographic, psychiatric and addiction-related variables. RESULTS: Suicidal ideation was reported in 62 (39%) of the Veterans interviewed. In a multivariable model, only inadequate SQ was associated with suicidal ideation. Short sleepers were more likely to endorse suicidal ideation and have attempted suicide in the past year. In addition, older age, inadequate financial status, and the presence of a psychiatric disorder were also significantly associated with suicidal ideation in most of the adjusted models. CONCLUSION: Given their association with suicidal ideation, insomnia symptoms in Veterans misusing alcohol should prompt an assessment of underlying psychiatric and social factors.

Insomnia in alcohol dependence: predictors of symptoms in a sample of veterans referred from primary care.

OBJECTIVE: Patients with alcohol dependence presenting for treatment may have multiple associated co-morbid conditions and limited social supports, which complicate treatment. Each of these factors has been independently associated with complaints of insomnia. In this preliminary study, we investigated the relations between insomnia complaints and socio-demographic factors and psychiatric co-morbidity in treatment-seeking patients with alcohol dependence. METHOD: We conducted a retrospective chart review on 84 consecutive patients referred to the Behavioral Health Laboratory of the Philadelphia Veterans Affairs Medical Center for evaluation of psychiatric and substance use disorders. Patients met DSM-IV diagnostic criteria for alcohol dependence and completed a series of self-assessments of sleep. Univariate and multivariable analyses were used to examine the relations amongst the variables of interest. RESULTS: In multivariable models, Sleep Latency was significantly greater in individuals without partners (p = .01), those with psychiatric disorders (p = .03) and smokers (p = .01), with a non-significant trend for those with past-year suicidal ideation. No significant predictor of Wake Time After Sleep Onset was seen. Poor Sleep Quality was predicted by younger age (OR = .93 [.88, .98], p = .004) and the presence of a psychiatric disorder (OR = 20.80 [4, 102], p = .0002), with a non-significant trend for suicidal ideation. CONCLUSIONS: Insomnia symptoms in treatment-seeking alcohol dependent patients should prompt consideration of the individuals' psychiatric and psychosocial features.

Cognitive behavioral therapy for insomnia comorbid with COPD is feasible with preliminary evidence of positive sleep and fatigue effects.

BACKGROUND: Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep. Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain). However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies. The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning. METHODS: The study had two phases. In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability. Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist. RESULTS: Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE. Participants indicated that both interventions were acceptable. Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000). Significant positive effects were noted for depressed mood after WE (P = 0.005). CONCLUSION: Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses.

Few changes observed in polysomnographic-assessed sleep before and after completion of chemotherapy.

OBJECTIVE: Sleep disturbance is prevalent among patients undergoing chemotherapy and is strongly associated with cancer-related fatigue (CRF). However, little objective evidence has been gathered on the patterns of sleep before and following chemotherapy. METHODS: Twenty-six patients scheduled to receive chemotherapy were recruited. Sleep parameters were assessed by in-lab polysomnography (PSG) for two consecutive nights prior to first chemotherapy, approximately 3weeks following the patients' last chemotherapy, and 3months following the last treatment. Fatigue was measured on the first night of each of the two-night PSG assessments. We focus on Slow-Wave Sleep (SWS) as we hypothesized that a decrease of this restorative phase of sleep might be implicated in CRF. RESULTS: Repeated-measures analyses examining changes from baseline to the later time points in the proportion of time asleep spent in each of the four sleep architecture stages (Stage 1, Stage 2, SWS, and REM sleep) were non-significant, all Ps>0.41. Canonical correlation analysis showed that the proportion of time spent in SWS was not significantly correlated with any of the three CRF measures at any of the three assessment points, P=0.28. CONCLUSIONS: Sleep architecture is not affected by cancer treatment. No evidence of an association between CRF and SWS, or alterations in SWS, was found.

The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain.

STUDY OBJECTIVES: To assess the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in patients with non-malignant chronic pain. METHODS: Twenty-eight subjects with chronic neck and back pain were stratified according to gender, age, and ethnicity, then assigned to one of the two treatment groups: CBT-I or a contact control condition. INTERVENTION: Eight weeks of CBT-I including sleep restriction, stimulus control, sleep hygiene, and one session of cognitive therapy devoted to catastrophic thoughts about the consequences of insomnia. MEASUREMENTS AND RESULTS: Outcomes included sleep diary assessments of sleep continuity, pre-post measures of insomnia severity (ISI), pain (Multidimensional Pain Inventory), and mood (BDI and POMS). Subjects receiving CBT-I (n=19), as compared to control subjects (n=9), exhibited significant decreases in sleep latency, wake after sleep onset, number of awakenings, and significant increase in sleep efficiency. The diary findings were paralleled by significant changes in the ISI (p=0.05). Significant improvement (p=0.03) was found on the Interference Scale of the Multidimensional Pain Inventory. The groups did not significantly differ on mood measures or measures of pain severity. CONCLUSIONS: CBT-I was successfully applied to patients experiencing chronic pain. Significant improvements were found in sleep as well as in the extent to which pain interfered with daily functioning. The observed effect sizes for the sleep outcomes appear comparable to or better than meta-analytic norms for subjects with Primary Insomnia.

Cancer-related fatigue and sleep disorders.

Sleep disorders, such as difficulty falling asleep, problems maintaining sleep, poor sleep efficiency, early awakening, and excessive daytime sleepiness, are prevalent in patients with cancer. Such problems can become chronic in some patients, persisting for many months or years after completion of cancer therapy. For patients with cancer, sleep is potentially affected by a variety of factors, including the biochemical changes associated with the process of neoplastic growth and anticancer treatments, and symptoms that frequently accompany cancer, such as pain, fatigue, and depression. Fatigue is highly prevalent and persistent in patients with cancer and cancer survivors. Although cancer-related fatigue and cancer-related sleep disorders are distinct, a strong interrelationship exists between these symptoms, and a strong possibility exists that they may be reciprocally related. The majority of studies that have assessed both sleep and fatigue in patients with cancer provide evidence supporting a strong correlation between cancer-related fatigue and various sleep parameters, including poor sleep quality, disrupted initiation and maintenance of sleep, nighttime awakening, restless sleep, and excessive daytime sleepiness. This paper reviews the data from these studies with a view toward suggesting further research that could advance our scientific understanding both of potential interrelationships between sleep disturbance and cancer-related fatigue and of clinical interventions to help with both fatigue and sleep disturbance. Disclosure of potential conflicts of interest is found at the end of this article.

A longitudinal study of depression, pain, and stress as predictors of sleep disturbance among women with metastatic breast cancer.

OBJECTIVE: Sleep disturbances are common among women with breast cancer and can have serious consequences. The present study examined depression, pain, life stress, and participation in group therapy in relation to sleep disturbances in a sample of women with metastatic breast cancer. METHODS: Ninety-three women with metastatic breast cancer participated in a large intervention trial examining the effect of the group therapy on their symptoms. They completed measures of depression, pain, life stress, and sleep disturbance at baseline, 4, 8 and 12 months. RESULTS: The results showed that higher initial levels of depression at baseline predicted problems associated with getting up in the morning, waking up during the night, and daytime sleepiness. Increases in depression over the course of 12 months were associated with fewer hours of sleep, more problems with waking up during the night and more daytime sleepiness. Higher levels of pain at baseline predicted more problems getting to sleep. Increases in pain predicted more difficulty getting to sleep and more problems waking up during the night. Greater life stress at baseline predicted more problems getting to sleep and more daytime sleepiness. CONCLUSIONS: Depression, pain, and life stress scores were each associated with different types of negative change in self-reported sleep disturbances. Depression, especially worsening depression, was associated with the greatest number of types of negative change. The relationships found between sleep disturbance and depression, pain, and life stress suggest specific ways to address the problem of sleep disturbance for women with metastatic breast cancer and show how different types of disturbed sleep may be clinical markers for depression, pain, or life stress in this population.

Suicidal ideation in outpatients with chronic musculoskeletal pain: an exploratory study of the role of sleep onset insomnia and pain intensity.

OBJECTIVES: Sleep disturbance, depression, and heightened risk of suicide are among the most clinically significant sequelae of chronic pain. While sleep disturbance is associated with suicidality in patients with major depression and is a significant independent predictor of completed suicide in psychiatric patients, it is not known whether sleep disturbance is associated with suicidal behavior in chronic pain. This exploratory study evaluates the importance of insomnia in discriminating suicidal ideation in chronic pain relative to depression severity and other pain-related factors. METHODS: Fifty-one outpatients with non-cancer chronic pain were recruited. Subjects completed a pain and sleep survey, the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, and the Multidimensional Pain Inventory. Subjects were classified as "suicidal ideators" or "non-ideators" based on their responses to BDI-Item 9 (Suicide). Bivariate analyses and multivariate discriminant function analyses were conducted. RESULTS: Twenty-four percent reported suicidal ideation (without intent). Suicidal ideators endorsed higher levels of: sleep onset insomnia, pain intensity, medication usage, pain-related interference, affective distress, and depressive symptoms (P < 0.03). These 6 variables were entered into stepwise discriminant function analyses. Two variables predicted group membership: Sleep Onset Insomnia Severity and Pain Intensity, respectively. The discriminant function correctly classified 84.3% of the cases (P < 0.0001). DISCUSSION: Chronic pain patients who self-reported severe and frequent initial insomnia with concomitant daytime dysfunction and high pain intensity were more likely to report passive suicidal ideation, independent from the effects of depression severity. Future research aimed at determining whether sleep disturbance is a modifiable risk factor for suicidal ideation in chronic pain is warranted.