Effects of a Triage Checklist to Optimize Insomnia Treatment Outcomes and Reduce Hypnotic Use: The RESTING Study.

STUDY OBJECTIVES: Evaluate a triaged stepped-care strategy among adults 50 and older with insomnia disorder. METHODS: Participants (N=245) were classified at baseline by a Triage-Checklist. Those projected to do better if they start treatment with therapist versus digitally delivered CBT-I (tCBT-I versus dCBT-I) constituted the YES stratum (n=137); the rest constituted the NO stratum (n=108). Participants were randomized within stratum to a strategy that utilized only dCBT-I (ONLN) or to a strategy that prospectively allocated the first step of care to dCBT-I or tCBT-I based on the Triage-Checklist and switched dCBT-I non-responders at 2-months to tCBT-I (STEP). Co-primary outcomes were the insomnia severity index (ISI) and the average nightly amount of prescription hypnotic medications used (MEDS), assessed at 2,4,6,9, and 12 months post-randomization. RESULTS: Mixed effects models revealed that, compared to ONLN, participants in STEP had greater reductions in ISI (p=0.001; η2=0.01) and MEDS (p=0.019, η2=0.01). Within the YES stratum, compared to ONLN, those in STEP had greater reductions in ISI (p=0.0001, η2=0.023) and MEDS (p=0.018, η2=0.01). Within the ONLN arm, compared to the YES stratum, those in the NO stratum had greater reductions in ISI (p=0.015, η2=0.01) but not in MEDS. Results did not change with treatment-dose covariate adjustment. CONCLUSIONS: Triaged-stepped care can help guide allocation of limited CBT-I treatment resources to promote effective and safe treatment of chronic insomnia among middle age and older adults. Further refinement of the Triage-Checklist and optimization of the timing and switching criteria may improve the balance between effectiveness and use of resources.

Patient perceptions of digital and therapist-led CBT for insomnia: A qualitative study.

OBJECTIVES: Technology has the potential to increase access to evidence-based insomnia treatment. Patient preferences/perceptions of automated digital cognitive behavior therapy for insomnia (CBTI) and telehealth-delivered CBTI remain largely unexplored among middle-aged and older adults. Using a qualitative approach, the current study describes patients' reasons for participating in the clinical trial, preferences for digital CBTI (dCBTI) versus therapist-led CBTI, patient attitudes toward dCBTI, and patient attitudes toward telehealth-delivered therapist-led CBTI. METHOD: Middle-aged and older adults (N = 80) completed a semi-structured interview before CBTI exposure. Qualitative responses were coded, and themes were inductively extracted. RESULTS: Most (62.5%) of the participants expressed a preference for therapist-led CBTI to dCBTI. Convenience was the most commonly reported advantage of dCBTI (n = 55) and telehealth-delivered CBTI (n = 65). Decreasing transit time and pandemic-related health concerns were identified as advantages to dCBTI and telehealth-delivered CBTI. Lack of human connection and limited personalization were perceived as disadvantages of dCBTI. Only three participants reported technological barriers to dCBTI and telehealth-delivered CBTI. CONCLUSION: Findings suggest that, despite an overall preference for therapist-led treatment, most middle-aged and older adults are open to dCBTI. As both dCBTI and telehealth-delivered CBTI are perceived as convenient, these modalities offer the potential to increase access to insomnia care.

Perspectives on increasing the impact and reach of CBT-I.

Cognitive behavioral therapy for insomnia is now recognized as the front-line treatment for chronic insomnia, yet many challenges remain in improving its impact and reach. This manuscript describes our perspective on some of these challenges. Based on the literature that maladaptive cognitions predict low adherence and that high levels of cognitive-emotional hyperarousal may be associated with poor outcomes, we propose added focus on cognitive therapy strategies in CBT-I. Specifically, we propose broadening the range of traditional cognitive therapy strategies, utilizing acceptance-based strategies, and fuller integration of the broadened range of cognitive strategies into CBT-I throughout the course of treatment. We also highlight a few other promising emerging approaches to enhance the impact of CBT-I. These include involving partners to promote adherence with CBT-I treatment recommendations, using culturally relevant treatment adaptations to increase retention of patients in treatment, and using strategies for timely identification of barriers to engagement. We propose broadening the public health impact of CBT-I by integrating support for reduction in long-term use of hypnotic sleep medications, which is in line with current medical guidelines. We advocate for a case conceptualization-based approach for implementing CBT-I in a patient-centered manner, flexibly, yet with fidelity, to enhance its impact by addressing the factors above. For increasing the reach of CBT-I, we discuss the need to train more clinicians and ways to combine therapist and digital deliveries of CBT-I, highlighting stepped care strategies.

Randomized controlled trial of cognitive behavioral therapy for perinatal insomnia: postpartum outcomes.

STUDY OBJECTIVES: This study aimed to assess the effectiveness of cognitive behavioral therapy for insomnia (CBTI) during the postpartum period as part of a larger randomized controlled trial of CBTI on perinatal insomnia. METHODS: A total of 179 women of 18-30 gestational weeks with insomnia disorder were randomly assigned to CBTI or an active control (CTRL) therapy. Participants were assessed between 18 and 32 weeks of pregnancy at baseline, after the intervention during pregnancy, and at 8, 18, and 30 weeks postpartum. The primary outcomes were Insomnia Severity Index (ISI) scores and total awake time, defined as minutes awake during the sleep opportunity period, assessed with actigraphy and sleep diaries. Included in the analyses were women who provided data for at least 1 of 3 postpartum assessments (68 in CBTI; 61 in CTRL). RESULTS: Piecewise mixed-effects models revealed a main effect reflecting reduction in ISI scores from 8-18 weeks postpartum (P = .036) and a nonsignificant increase from 18-30 weeks; significant effects for group allocation were present only in week 30 (P = .042). CTRL participants reported significantly longer time awake, excluding time spent caring for the infant, at each postpartum assessment; time awake at night caring for the infant did not differ between groups. There was no significant group difference in the postpartum trajectory of actigraphy-measured total awake time, the two diary measures of time awake (P values > .05). CBTI participants with at least 50% reduction in ISI during pregnancy had consistently stable ISI scores (mean < 6) during the postpartum period; those in the CTRL group had variable ISI scores over time with large individual differences. CONCLUSIONS: For women with insomnia disorder during pregnancy, CBTI initiated during pregnancy conferred postpartum benefits in terms of wakefulness after sleep onset (excluding time spent caring for the infant) and insomnia severity, though the latter emerged only later in the postpartum period. These findings underscore the importance of treating insomnia during pregnancy, a conclusion that is further supported by our finding that pregnant women who responded to insomnia treatment during pregnancy experienced better sleep in the postpartum period. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrials.gov; Name: Treatment for Insomnia During Pregnancy; URL: https://www.clinicaltrials.gov/ct2/show/NCT01846585; Identifier: NCT01846585. CITATION: Manber R, Bei B, Suh S, et al. Randomized controlled trial of cognitive behavioral therapy for perinatal insomnia: postpartum outcomes. J Clin Sleep Med. 2023;19(8):1411-1419.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.

Background: The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined. Methods: We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) phenotype. Findings: The median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS, majority were female, and obesity (BMI > 30 Kg/m2) (P = 0.00377895) and worse functional status (P = 0.0110474) were significantly associated with ME/CFS. Interpretations: Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.

Beliefs about prescription sleep medications and interest in reducing hypnotic use: an examination of middle-aged and older adults with insomnia disorder.

STUDY OBJECTIVES: To examine beliefs about prescription sleep medications (hypnotics) among individuals with insomnia disorder seeking cognitive behavioral therapy for insomnia and predictors of wishing to reduce use. METHODS: Baseline data was collected from 245 adults 50 years and older enrolled in the "RCT of the Effectiveness of Stepped-Care Sleep Therapy in General Practice" study. T-tests compared characteristics of prescription sleep medication users with those of nonusers. Linear regression assessed predictors of patients' beliefs about sleep medication necessity and hypnotic-related concerns. Among users, we examined predictors of wishing to reduce sleep medications, including perceived hypnotic dependence, beliefs about medications, and demographic characteristics. RESULTS: Users endorsed stronger beliefs about the necessity of sleep medications and less concern about potential harms than nonusers (P < .01). Stronger dysfunctional sleep-related cognitions predicted greater beliefs about necessity and concern about use (P < .01). Patients wishing to reduce sleep medications reported greater perceived hypnotic dependence than those disinterested in reduction (P < .001). Self-reported dependence severity was the strongest predictor of wishing to reduce use (P = .002). CONCLUSIONS: Despite expressing strong beliefs about necessity, and comparatively less concern about taking sleep medications, three-quarters of users wished to reduce prescription hypnotics. Results may not generalize to individuals with insomnia not seeking nonpharmacological treatments. Upon completion, the "RCT of the Effectiveness of Stepped-Care Sleep Therapy in General Practice" study will provide information about the extent to which therapist-led and digital cognitive behavioral therapy for insomnia contribute to prescription hypnotic reduction. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The RESTING Insomnia Study: Randomized Controlled Study on Effectiveness of Stepped-Care Sleep Therapy (RESTING); URL: https://clinicaltrials.gov/ct2/show/NCT03532282; Identifier: NCT03532282. CITATION: Tully IA, Kim JP, Simpson N, et al. Beliefs about prescription sleep medications and interest in reducing hypnotic use: an examination of middle-aged and older adults with insomnia disorder. J Clin Sleep Med. 2023;19(7):1247-1257.

Alterations of pain pathways by experimental sleep disturbances in humans: central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways.

STUDY OBJECTIVES: There is strong evidence that sleep disturbances are an independent risk factor for the development of chronic pain conditions. The mechanisms underlying this association, however, are still not well understood. We examined the effect of experimental sleep disturbances (ESDs) on three pathways involved in pain initiation/resolution: (1) the central pain-inhibitory pathway, (2) the cyclooxygenase (COX) pathway, and (3) the endocannabinoid (eCB) pathway. METHODS: Twenty-four healthy participants (50% females) underwent two 19-day long in-laboratory protocols in randomized order: (1) an ESD protocol consisting of repeated nights of short and disrupted sleep with intermittent recovery sleep; and (2) a sleep control protocol consisting of nights with an 8-hour sleep opportunity. Pain inhibition (conditioned pain modulation, habituation to repeated pain), COX-2 expression at monocyte level (lipopolysaccharide [LPS]-stimulated and spontaneous), and eCBs (arachidonoylethanolamine, 2-arachidonoylglycerol, docosahexaenoylethanolamide [DHEA], eicosapentaenoylethanolamide, docosatetraenoylethanolamide) were measured every other day throughout the protocol. RESULTS: The central pain-inhibitory pathway was compromised by sleep disturbances in females, but not in males (p < 0.05 condition × sex effect). The COX-2 pathway (LPS-stimulated) was activated by sleep disturbances (p < 0.05 condition effect), and this effect was exclusively driven by males (p < 0.05 condition × sex effect). With respect to the eCB pathway, DHEA was higher (p < 0.05 condition effect) in the sleep disturbance compared to the control condition, without sex-differential effects on any eCBs. CONCLUSIONS: These findings suggest that central pain-inhibitory and COX mechanisms through which sleep disturbances may contribute to chronic pain risk are sex specific, implicating the need for sex-differential therapeutic targets to effectively reduce chronic pain associated with sleep disturbances in both sexes. CLINICAL TRIALS REGISTRATION: NCT02484742: Pain Sensitization and Habituation in a Model of Experimentally-induced Insomnia Symptoms. https://clinicaltrials.gov/ct2/show/NCT02484742.

Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder.

STUDY OBJECTIVES: Examine bidirectional associations between daytime napping and nighttime sleep among pregnant individuals with insomnia disorder. METHODS: We used baseline data from a randomized controlled trial of insomnia treatment during pregnancy (n = 116). Participants in their second or third trimester of pregnancy self-reported daytime napping and nighttime sleep parameters using a sleep diary and wore an Actiwatch-2 during the same 7-day period. Linear regression models, accounting for intraindividual correlation, were used to estimate associations between daytime napping and nighttime sleep parameters (duration, efficiency, quality, awakenings). Models were also stratified by trimester of pregnancy. RESULTS: Sixty-three percent of participants reported napping on at least 1 day. Among participants in the second trimester (65%), napping 15-59 minutes was associated with 6.3% greater self-reported sleep efficiency (95% confidence interval: 2.3, 10.2) and 0.5 units greater self-reported sleep quality (95% confidence interval: 0.0, 0.9) that night; napping 60+ minutes was associated with 0.6 hours shorter actigraphy-measured sleep duration (95% confidence interval: -1.0, -0.2). Napping was not associated with nighttime sleep overall or during the third trimester. Nighttime sleep parameters were not associated with napping duration the following day. CONCLUSIONS: Among pregnant individuals with insomnia in the second trimester, short napping duration was associated with higher self-reported sleep efficiency and quality; long napping duration was associated with shorter actigraphy-measured sleep duration. Additional research is needed to examine the interaction between nap duration and nap timing. In the future, these results may lead to more nuanced recommendations for daytime napping among pregnant individuals with insomnia disorder. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment for Insomnia during Pregnancy; URL: https://clinicaltrials.gov/ct2/show/NCT01846585; Identifier: NCT01846585. CITATION: Badon SE, Dietch R, Simpson N, Lyell DJ, Manber R. Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder. J Clin Sleep Med. 2023;19(2):371-377.

Differential effects of an experimental model of prolonged sleep disturbance on inflammation in healthy females and males.

Sleep disturbances, including disrupted sleep and short sleep duration, are highly prevalent and are prospectively associated with an increased risk for various widespread diseases, including cardiometabolic, neurodegenerative, chronic pain, and autoimmune diseases. Systemic inflammation, which has been observed in populations experiencing sleep disturbances, may mechanistically link disturbed sleep with increased disease risks. To determine whether sleep disturbances are causally responsible for the inflammatory changes reported in population-based studies, we developed a 19-day in-hospital experimental model of prolonged sleep disturbance inducing disrupted and shortened sleep. The model included delayed sleep onset, frequent nighttime awakenings, and advanced sleep offset, interspersed with intermittent nights of undisturbed sleep. This pattern aimed at providing an ecologically highly valid experimental model of the typical sleep disturbances often reported in the general and patient populations. Unexpectedly, the experimental sleep disturbance model reduced several of the assessed proinflammatory markers, namely interleukin(IL)-6 production by monocytes and plasma levels of IL-6 and C-reactive protein (CRP), presumably due to intermittent increases in the counterinflammatory hormone cortisol. Striking sex differences were observed with females presenting a reduction in proinflammatory markers and males showing a predominantly proinflammatory response and reductions of cortisol levels. Our findings indicate that sleep disturbances causally dysregulate inflammatory pathways, with opposing effects in females and males. These results have the potential to advance our mechanistic understanding of the pronounced sexual dimorphism in the many diseases for which sleep disturbances are a risk factor.

Stepped care management of insomnia co-occurring with sleep apnea: the AIR study protocol.

BACKGROUND: Obstructive sleep apnea (OSA) and insomnia are commonly co-occurring conditions that amplify morbidity and complicates the management of affected patients. Unfortunately, previous research provides limited guidance as to what constitutes the best and most practical management approach for this comorbid patient group. Some preliminary studies show that when cognitive behavioral insomnia therapy (CBT-I) is combined with standard OSA therapies for these patients, outcomes are improved. However, the dearth of trained providers capable of delivering CBT-I has long served as a pragmatic barrier to the widespread use of this therapy in clinical practice. The emergence of sophisticated online CBT-I (OCBT-I) programs could improve access, showing promising reductions in insomnia severity. Given its putative scalability and apparent efficacy, some have argued OCBT-I should represent a 1st-stage intervention in a broader stepped care model that allocates more intensive and less assessable therapist-delivered CBT-I (TCBT-I) only to those who show an inadequate response to lower intensity OCBT-I. However, the efficacy of OCBT-I as a 1st-stage therapy within a broader stepped care management strategy for insomnia comorbid with OSA has yet to be tested with comorbid OSA/insomnia patients. METHODS/DESIGN: This dual-site randomized clinical trial will use a Sequential Multiple Assignment Randomized Trial (SMART) design to test a stepped care model relative to standard positive airway pressure (PAP) therapy and determine if (1) augmentation of PAP therapy with OCBT-I improves short-term outcomes of comorbid OSA/insomnia and (2) providing a higher intensity 2nd-stage CBT-I to patients who show sub-optimal short-term outcomes with OCBT-I+PAP improves short and longer-term outcomes. After completing baseline assessment, the comorbid OSA/insomnia patients enrolled will be randomized to a 1st-stage therapy that includes usual care PAP + OCBT-I or UC (usual care PAP + sleep hygiene education). Insomnia will be reassessed after 8 weeks. OCBT-I recipients who meet "remission" criteria (defined as an Insomnia Severity Index score < 10) will continue PAP but will not be offered any additional insomnia intervention and will complete study outcome measures again after an additional 8 weeks and at 3 and 6 month follow-ups. OCBT-I recipients classified as "unremitted" after 8 weeks of treatment will be re-randomized to a 2nd-stage treatment consisting of continued, extended access to OCBT-I or a switch to TCBT-I. Those receiving the 2nd-stage intervention as well as the UC group will be reassessed after another 8 weeks and at 3- and 6-month follow-up time points. The primary outcome will be insomnia remission. Secondary outcomes will include subjective and objective sleep data, including sleep time, sleep efficiency, fatigue ratings, PAP adherence, sleepiness ratings, sleep/wake functioning ratings, and objective daytime alertness. DISCUSSION: This study will provide new information about optimal interventions for patients with comorbid OSA and insomnia to inform future clinical decision-making processes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03109210 , registered on April 12, 2017, prospectively registered.

RCT of the effectiveness of stepped-care sleep therapy in general practice: The RESTING study protocol.

Cognitive behavioral therapy for insomnia (CBT-I) is an effective, non-pharmacological intervention, designated by the American College of Physicians as the first-line treatment of insomnia disorder. The current randomized controlled study uses a Hybrid-Type-1 design to compare the effectiveness and implementation potential of two approaches to delivering CBT-I in primary care. One approach offers therapy to all patients through an automated, digital CBT-I program (ONLINE-ONLY). The other is a triaged STEPPED-CARE approach that uses a simple Decision Checklist to start patients in either digital or therapist-led treatment; patients making insufficient progress with digital treatment at 2 months are switched to therapist-led treatment. We will randomize 240 individuals (age 50 or older) with insomnia disorder to ONLINE-ONLY or STEPPED-CARE arms. The primary outcomes are insomnia severity and hypnotic medication use, assessed at baseline and at months 2, 4, 6, 9, and 12 after randomization. We hypothesize that STEPPED-CARE will be superior to ONLINE-ONLY in reducing insomnia severity and hypnotic use. We also aim to validate the Decision Checklist and explore moderators of outcome. Additionally, guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, we will use mixed methods to obtain data on the potential for future dissemination and implementation of each approach. This triaged stepped-care approach has the potential to improve sleep, reduce use of hypnotic medications, promote safety, offer convenient access to treatment, and support dissemination of CBT-I to a large number of patients currently facing barriers to accessing treatment. Clinical trial registration:NCT03532282.

Mothers' postpartum sleep disturbance is associated with the ability to sustain sensitivity toward infants.

BACKGROUND/OBJECTIVE: Infancy is a period of rapid development when the quality of caregiving behavior may be particularly consequential for children's long-term functioning. During this critical period for caregiving behavior, parents experience changes in their sleep that may affect their ability to provide sensitive care. The current study investigated the association of mothers' sleep disturbance with both levels and trajectories of maternal sensitivity during interactions with their infants. METHODS: At 18 weeks postpartum, mothers and their infants were observed during a home-based 10-minute "free play" interaction. Mothers' nighttime sleep was objectively measured using actigraphy and subjectively measured using sleep diaries. Maternal sensitivity was coded in two-minute intervals in order to characterize changes in sensitivity across the free play interaction. We used exploratory factor analysis to reduce the dimensionality of the objective and subjective measures of mothers' sleep, identifying a subjective sleep disturbance and an objective sleep continuity factor. RESULTS: Using multi-level modeling, we found that mothers with poorer objective sleep continuity evidenced decreasing sensitivity toward their infants across the interaction. Mothers' self-reports of sleep disturbance were not associated with maternal sensitivity. CONCLUSIONS: Although future research is necessary to identify the mechanisms that may explain the observed association between poor sleep continuity and the inability to sustain sensitivity toward infants, mothers' postpartum sleep continuity may be one factor to consider when designing interventions to improve the quality of caregiving. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01846585.

Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications.

Pain can be both a cause and a consequence of sleep deficiency. This bidirectional relationship between sleep and pain has important implications for clinical management of patients, but also for chronic pain prevention and public health more broadly. The review that follows will provide an overview of the neurobiological evidence of mechanisms thought to be involved in the modulation of pain by sleep deficiency, including the opioid, monoaminergic, orexinergic, immune, melatonin, and endocannabinoid systems; the hypothalamus-pituitary-adrenal axis; and adenosine and nitric oxide signaling. In addition, it will provide a broad overview of pharmacological and non-pharmacological approaches for the management of chronic pain comorbid with sleep disturbances and for the management of postoperative pain, as well as discuss the effects of sleep-disturbing medications on pain amplification.

Cognitive Behavioral Therapy for Prenatal Insomnia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of cognitive behavioral therapy for insomnia during pregnancy. METHODS: Randomized, unmasked, 3-site controlled trial. Participants were randomly allocated to cognitive behavioral therapy for insomnia (a first-line, empirically supported psychosocial intervention that addresses sleep-related behaviors and cognitions) or a control intervention consisting of imagery exercises that paired patient-identified distressing nighttime experiences with patient-identified neutral images. Participants were eligible if they met diagnostic criteria for insomnia disorder and were between 18 and 32 weeks of gestation. Patients were ineligible if they met diagnostic criteria for major psychiatric disorders, including depression, or were receiving nonstudy treatments that could affect sleep (or both). The primary outcome was the Insomnia Severity Index score, a validated brief questionnaire, with scores between 14 and 21 representing clinically meaningful insomnia of moderate severity, scores higher than 21 representing severe insomnia, and scores less than 8 representing no insomnia. Secondary outcomes included remission of insomnia (Insomnia Severity Index score less than 8), objectively measured and self-reported time awake (ie, total wake time), and the Edinburgh Postnatal Depression Scale score. All outcomes were measured weekly. Analysis included 48 participants who did not complete treatment. We estimated that 184 women would be required to have 80% power, with a two-tailed test, to detect a moderate Cohen's d effect size (.5) with α=.05. RESULTS: Between May 2013 and April 2017, 194 pregnant women were randomized and 149 completed treatment; 179 with available baseline data (92%) were ultimately analyzed, 89 in the cognitive therapy group and 90 in the control group. Women assigned to cognitive behavioral therapy for insomnia experienced significantly greater reductions in insomnia severity (scores decreased from 15.4±4.3 to 8.0±5.2 in the cognitive behavioral therapy group vs from 15.9±4.4 to 11.2±4.9 in the control therapy group [P<.001, d=0.5]). Remission of insomnia (to an Insomnia Severity Index score less than 8) disorder was attained by 64% of women in the cognitive behavioral therapy for insomnia group vs 52% in the control group. Women receiving cognitive behavioral therapy for insomnia experienced faster remission of insomnia disorder, with a median of 31 days vs 48 days in the control therapy (P<.001). Cognitive behavioral therapy for insomnia led to significantly greater reduction in self-reported but not objective total wake time and a small but significantly greater decline in Edinburgh Postnatal Depression Scale scores vs the control group. CONCLUSION: Cognitive behavioral therapy for insomnia is an effective nonpharmacologic treatment for insomnia during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01846585.

Heart rate variability rebound following exposure to persistent and repetitive sleep restriction.

While it is well established that slow-wave sleep electroencephalography (EEG) rebounds following sleep deprivation, very little research has investigated autonomic nervous system recovery. We examined heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) during four blocks of repetitive sleep restriction and sequential nights of recovery sleep. Twenty-one healthy participants completed the 22-day in-hospital protocol. Following three nights of 8-hr sleep, they were assigned to a repetitive sleep restriction condition. Participants had two additional 8-hr recovery sleep periods at the end of the protocol. Sleep EEG, HRV, and BRS were compared for the baseline, the four blocks of sleep restriction, and the second (R2) and third (R3) nocturnal recovery sleep periods following the last sleep restriction block. Within the first hour of each sleep period, vagal activation, as indexed by increase in high frequency (HF; HRV spectrum analysis), showed a rapid increase, reaching its 24-hr peak. HF was more pronounced (rebound) in R2 than during baseline (p < 0.001). The BRS increased within the first hour of sleep and was higher across all sleep restriction blocks and recovery nights (p = 0.039). Rebound rapid eye movement sleep was observed during both R2 and R3 (p = 0.004), whereas slow-wave sleep did not differ between baseline and recovery nights (p > 0.05). Our results indicate that the restoration of autonomic homeostasis requires a time course that includes at least three nights, following an exposure to multiple nights of sleep curtailed to about half the normal nightly amount.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

Chronic pain conditions are highly comorbid with insufficient sleep. While the mechanistic relationships between the 2 are not understood, chronic insufficient sleep may be 1 pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of 3 weeks of restricted sleep with limited recovery (5 nights of 4-hour sleep per night followed by 2 nights of 8-hour sleep per night) was compared with 3 weeks of 8-hour sleep per night (control protocol). Seventeen healthy adults participated, with 14 completing both 3-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared with the control protocol, participants in the sleep-restriction protocol experienced mild increases in spontaneous pain (P < 0.05). Heat-pain thresholds decreased after the first week of sleep restriction (P < 0.05) but normalized with longer exposure to sleep restriction. By contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both P < 0.05), although only in the past 2 weeks of the sleep-restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Repeating patterns of sleep restriction and recovery: Do we get used to it?

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.