Preliminary evidence of psychological improvements and increased maternal-fetal attachment associated with a mindfulness sleep programme: secondary analysis of uncontrolled data in 11 pregnant women with insomnia disorder.

Treating insomnia during pregnancy improves sleep and depressed mood. However, given well-established links between poor sleep and a broad spectrum of adverse maternal outcomes, the benefits of insomnia care may reach beyond sleep and depression. The present study evaluated the preliminary efficacy of 'Perinatal Understanding of Mindful Awareness for Sleep' (PUMAS)-a mindfulness sleep programme tailored to pregnancy that combines behavioural sleep strategies and meditation-for enhancing everyday mindfulness and maternal-fetal attachment, as well as for alleviating anxiety, repetitive thinking, and sleep-related daytime impairment. We conducted a secondary analysis of a single-arm proof-of-concept trial of 11 pregnant women with fifth edition of the Diagnostic and Statistical Manual of Mental Disorders diagnosed insomnia disorder who completed PUMAS (six sessions), which was delivered in an individual format via telemedicine video. Pre- and post-treatment outcomes included the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), Maternal-Fetal Attachment Scale (MFAS), Generalised Anxiety Disorder seven-item survey (GAD-7), Perseverative Thinking Questionnaire (PTQ), Daytime Insomnia Symptoms Response Scale (DISRS), and the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Scale (PROMIS-SRI). Symptom changes were evaluated with paired-samples t tests. Results showed PUMAS patients reported large increases in CAMS-R (Cohen's dz = 1.81) and medium-large increases in MFAS scores (Cohen's dz = 0.73). Moreover, PUMAS patients reported large reductions in scores on the GAD-7 (Cohen's dz = 1.09), PTQ (Cohen's dz = 1.26), DISRS (Cohen's dz = 1.38), and PROMIS-SRI (Cohen's dz = 1.53). Preliminary evidence suggests that a mindfulness-based perinatal sleep programme may benefit several domains of maternal wellbeing beyond sleep and depression. PUMAS substantially enhanced patient ratings of everyday mindfulness and maternal-fetal attachment, while reporting alleviations in anxiety, perseverative thinking, insomnia-focused rumination, and sleep-related daytime impairment.

Reducing cognitive arousal and sleep effort alleviates insomnia and depression in pregnant women with DSM-5 insomnia disorder treated with a mindfulness sleep program.

Objectives: Combining mindfulness with behavioral sleep strategies has been found to alleviate symptoms of insomnia and depression during pregnancy, but mechanisms for this treatment approach remain unclear. The present study examined nocturnal cognitive arousal and sleep effort as potential treatment mechanisms for alleviating insomnia and depression via a mindfulness sleep program for pregnant women. Methods: Secondary analysis from a proof-of-concept trial of 12 pregnant women with DSM-5 insomnia disorder who were treated with Perinatal Understanding of Mindful Awareness for Sleep (PUMAS), which places behavioral sleep strategies within a mindfulness framework. Data were collected across eight weekly assessments: pretreatment, six sessions, and posttreatment. Measures included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), pre-sleep arousal scale's cognitive factor (PSASC), and the Glasgow sleep effort scale (GSES). We used linear mixed modeling to test cognitive arousal and sleep effort as concurrent and prospective predictors of insomnia and depression. Results: Most patients reported high cognitive arousal before PUMAS (75.0%), which decreased to 8.3% after treatment. All insomnia remitters reported low cognitive arousal after treatment, whereas half of nonremitters continued reporting high cognitive arousal. Both nocturnal cognitive arousal and sleep effort were associated with same-week changes in insomnia throughout treatment, and sleep effort yielded a prospective effect on insomnia. Lower levels of nocturnal cognitive arousal and sleep effort prospectively predicted reductions in depression. Conclusions: The present study offers preliminary evidence that reducing sleep effort and nocturnal cognitive arousal may serve as key mechanisms for alleviating insomnia and depression via mindfulness-based insomnia therapy. ClinicalTrials.gov ID: NCT04443959.

Perinatal Understanding of Mindful Awareness for Sleep (PUMAS): A single-arm proof-of-concept clinical trial of a mindfulness-based intervention for DSM-5 insomnia disorder during pregnancy.

OBJECTIVES: Cognitive-behavioral therapy is effective for prenatal insomnia, but unresolved cognitive arousal limits patient outcomes. Therapies aimed at reducing cognitive arousal may benefit pregnant women with insomnia. This proof-of-concept trial evaluated Perinatal Understanding of Mindful Awareness for Sleep (PUMAS, which combines mindfulness with behavioral sleep strategies) on insomnia, depression, and cognitive arousal. METHODS: A single-arm trial of 12 pregnant women with DSM-5 insomnia disorder (n = 5/12 with comorbid depression) who received six sessions of PUMAS delivered individually via telemedicine. Pretreatment and posttreatment outcomes included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), pre-sleep arousal scale's cognitive factor (PSASC; nocturnal cognitive arousal), perinatal-focused rumination (appended to PSASC), and Glasgow sleep effort scale. RESULTS: Eleven of 12 patients completed all sessions. Intent-to-treat analyses revealed a 10.83-point reduction in ISI (Cohen's dz = 3.05), resulting in 83.3% insomnia remission. PUMAS produced large reductions in EPDS (Cohen's dz = 2.76 in depressed group), resulting in all five baseline depressed patients remitting from depression. PUMAS produced large reductions in nocturnal cognitive arousal, perinatal-focused rumination, and sleep effort (all Cohen's dzs>2.00). Patients were highly satisfied with PUMAS and identified the telemedicine format and meditation app as positive features of its delivery. Patients rated sleep restriction and guided meditations as the most helpful treatment components. CONCLUSION: Prenatal insomnia patients were highly engaged in PUMAS, which produced large acute reductions in insomnia, depression, and cognitive arousal. These findings support the concept and feasibility of PUMAS for pregnant women with insomnia who present with or without comorbid depression. GOV ID: NCT04443959.

Mindfulness and nocturnal rumination are independently associated with symptoms of insomnia and depression during pregnancy.

BACKGROUND: Insomnia and depression are highly prevalent perinatal complications. Ruminating on stress is etiologically implicated in both disorders, and ruminating while trying to fall asleep has been linked to insomnia and depression during pregnancy. Incompatible with rumination is everyday mindfulness, i.e., living with intentional and nonjudgmental awareness of internal and external experiences in the present moment. Responding to stress mindfully may protect against stress-related perinatal complications such as insomnia and depression. The present study described the association between everyday mindfulness and nocturnal rumination, and examined whether these trait characteristics were independently related to perinatal insomnia and depression. METHODS: Cross-sectional and secondary analysis of existing data from 65 pregnant women recruited from a multisite hospital in Metro Detroit, MI, USA. Subjects completed online surveys including the Insomnia Severity Index, Edinburgh Postnatal Depression Scale, Presleep Arousal Scale, and the revised Cognitive and Affective Mindfulness Scale. RESULTS: Over half (53.8%) of women screened positive for clinical insomnia and 12.3% screened positive for major depression. Women high in mindfulness, relative to those low in mindfulness, reported less nocturnal rumination (Cohen's d=1.16), insomnia symptoms (Cohen's d=1.24), and depressive symptoms (Cohen's d=1.35). Multivariate linear regression revealed that both mindfulness (ß=-.24, p=.03) and rumination (ß=.38, p<.01) were independently associated with insomnia. Similarly, a multivariate model showed that mindfulness (ß=-.41, p<.001) and rumination (ß=.35, p<.01) were independently associated with depression. CONCLUSIONS: Ruminating in bed at night is strongly associated with insomnia and depression during pregnancy, whereas mindfulness may potentially protect against these stress-related perinatal complications.

Can the Orexin Antagonist Suvorexant Preserve the Ability to Awaken to Auditory Stimuli While Improving Sleep?

STUDY OBJECTIVES: The safety profile of the dual orexin receptor antagonists (DORAs) are currently unknown with regard to nocturnal responsivity among people with insomnia. We compared the auditory awakening thresholds (AATs) of the DORA suvorexant (10 and 20 mg) versus placebo in 12 individuals with DSM-5 insomnia. METHODS: The study used a double-blind, placebo-controlled, three-way crossover design. Participants were randomly assigned to a treatment sequence that included placebo, suvorexant 10 mg, and suvorexant 20 mg. At the time of maximum drug concentration, auditory tones were played during stable stage N2 sleep. Tones increased by 5-decibel (db) increments until the participant awakened. The db at awakening was recorded as the AAT and compared between conditions. The proportion of awakenings higher than 85 db was also compared between conditions. Finally, sensitivity analyses were also conducted using surrounding thresholds (80 db and 90 db). RESULTS: The mean AAT did not differ significantly between either dose of suvorexant compared to placebo. Moreover, the proportions of individuals who remained asleep at the AAT 85 db cutoff did not differ across conditions. In addition, wake after sleep onset decreased and total sleep time increased in the suvorexant 20 mg condition compared to placebo. CONCLUSIONS: Suvorexant (10 and 20 mg) preserved the ability to respond to nocturnal stimuli, whereas the 20-mg dose improved the sleep of people with insomnia. This suggests that DORAs such as suvorexant can effectively treat insomnia while allowing patients to awaken to nocturnal stimuli in the environment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: A Phase IV 3-Way Double-blind, Randomized, Crossover Study to Compare the Awakening Threshold Effects (Responsivity) of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs; Identifier NCT03312517; URL: https://clinicaltrials.gov/ct2/show/NCT03312517. CITATION: Drake CL, Kalmbach DA, Cheng P, Roth T, Tran KM, Cuamatzi-Castelan A, Atkinson R, SinghM, Tonnu CV, Fellman-Couture C. Can the orexin antagonist suvorexant preserve the ability to awaken to auditory stimuli while improving sleep? J Clin Sleep Med. 2019;15(9):1285-1291.

Shift work sleep disorder: burden of illness and approaches to management.

More than 6 million Americans work night shifts on a regular or rotating basis. The negative consequences of shift work have been established, and recent evidence suggests that patients with shift work sleep disorder (SWSD) are at increased risk of these consequences and co-morbidities. SWSD is a relatively common but under-recognised, and hence undertreated, condition with potentially serious medical, social, economic and quality-of-life consequences. In addition to increased risk of gastrointestinal and cardiovascular disease, patients with SWSD experience clinically significant excessive sleepiness or insomnia associated with work during normal sleep times, which has important safety implications. A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. However, most studies evaluating pharmacological therapies and nonpharmacological interventions simulate night-shift work under conditions that may not accurately reflect real-world activities. Pharmacological and nonpharmacological countermeasures evaluated mostly in simulated laboratory conditions have been shown to improve alertness or sleep in shift workers but have not yet been evaluated in patients with SWSD. To date, three randomised, double-blind clinical studies have evaluated pharmacological therapies in patients with SWSD. These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. In conclusion, SWSD is a common condition that remains under-recognised and undertreated. Further research is needed to evaluate different treatment approaches for this condition, to clarify the substantial health and economic consequences of SWSD, and to determine the potential for interventions or treatments to reduce the negative consequences of this condition.

Correlation of the acid-sensitivity of polyethylene glycol daunorubicin conjugates with their in vitro antiproliferative activity.

Polyethylene glycol conjugates with linkers of varying acid-sensitivity were prepared by reacting five maleimide derivatives of daunorubicin containing an amide bond (1) or acid-sensitive carboxylic hydrazone bonds (2-5) with alpha-methoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 20000) or alpha,omega-bis-thiopropionic acid amide poly(ethylene glycol) (MW 20000). The polymer drug derivatives were designed to release daunorubicin inside the tumor cell by acid-cleavage of the hydrazone bond after uptake of the conjugate by endocytosis. In subsequent cell culture experiments, the order of antitumor activity of the PEG daunorubicin conjugates correlated with their acid-sensitivity as determined by HPLC (cell lines: BXF T24 bladder carcinoma and LXFL 529L lung cancer cell line; assay: propidium iodide fluorescence assay). The acid-sensitivity of the link between PEG and daunorubicin is therefore an important parameter for in vitro efficacy.