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Background: Patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) experience many distressing symptoms. One frequently reported symptom is insomnia. There are unique issues about HD treatments and schedules that disrupt regular sleep/wake routines and possibly contribute to the high severity of insomnia. Despite evidence for broad-ranging health effects of insomnia, very few clinical trials have tested the efficacy of treatments for HD patients. Cognitive-behavioral therapy for insomnia (CBT-I) is a recommended first-line therapy but largely inaccessible to HD patients in the United States, partly because they commit considerable amounts of time to thrice-weekly dialysis treatments. Another important reason could be the logistical and reimbursement challenges associated with providing behavioral health care at the dialysis center. CBT-I delivered by telehealth can overcome barriers to access, but its efficacy has never been rigorously tested for these patients. Pharmacotherapy is the most widely used treatment for insomnia; however, some drugs presently used are unsafe as they are associated with a higher risk for death for HD patients (benzodiazepines and zolpidem-like drugs). The efficacy and safety of other medications (trazodone) for the treatment of insomnia has never been tested for patients treated with HD.Methods: This trial tests the short- and long-term comparative effectiveness of 6-week treatment with telehealth CBT-I, trazodone, or medication placebo. This will be accomplished with a randomized controlled trial (RCT) in which 126 participants treated with HD in community-based dialysis facilities with chronic insomnia will be assigned 1:1:1 to telehealth CBT-I, trazodone, or medication placebo, respectively; short-term effectiveness of each treatment arm will be determined at the end of 6-weeks of treatment and long-term effectiveness at 25-weeks. The primary and secondary patient-reported outcomes will be assessed with computer-based telephone interviewing by research scientists blinded to treatment assignment; additional secondary outcomes will be assessed by participant interview and actigraphy.Discussion: This clinical RCT will provide the first evidence for the comparative effectiveness of two distinct approaches for treating chronic insomnia and other patient-reported outcomes for patients receiving maintenance HD.Trial Registration: NCT03534284 May 23, 2018. SLEEP-HD Protocol Version: 1.3.4 (7/22/2020). [ABSTRACT FROM AUTHOR]

Background: Among the over 5 million informal caregivers for patients with Alzheimer's disease (AD) in the United States (US), over 60% experience insomnia. Research on insomnia treatment efficacy in AD caregivers is limited. An ongoing randomized non-inferiority clinical trial, the Caregiver Sleep Research study, is evaluating whether mindfulness meditation is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) in the treatment of insomnia in AD caregivers. The present report examines estimated intervention costs in this ongoing trial.Methods: Micro-costing was used to itemize and abstract costs of the two interventions: a mindfulness-based intervention known as mindful awareness practices for insomnia (MAP-I); and CBT-I. This approach involves collecting detailed data on resources utilized and the unit costs of those resources, thereby revealing actual resource use and economic costs for each treatment arm. Personnel time, patient time, and supplies were inventoried, and unit costs were applied. Caregiver time costs, including travel, were based on US Labor Bureau home-health aide national mean hourly wages; instructor/staff costs were based on hourly wages. Per-participant and program costs were calculated assuming individual- and group-delivery to reflect real-world implementation. Sensitivity analyses evaluated robustness of estimates.Results: From the societal perspective, per-participant MAP-I costs were $1884 for individual and $1377 for group delivery; for CBT-I, these costs were $3978 and $1981, respectively. Compared with CBT-I, MAP-I provided cost savings of $2094 (53%) and $604 (30%) per treated caregiver for individual and group delivery, respectively. From the US healthcare system perspective, MAP-I vs. CBT-I participant savings were $1872 (65%) for individual and $382 (44%) for group interventions, respectively. For MAP-I and CBT-I, instructor in-class time was the highest cost component. Results were most sensitive to combined instructor time costs.Conclusions: Treatment of insomnia with MAP-I, compared to CBT-I, yields substantial cost savings for society and the healthcare system. With this potential for cost savings, results of the ongoing non-inferiority trial have critical implications for insomnia treatment dissemination and its benefits to AD caregivers and other community populations with insomnia. [ABSTRACT FROM AUTHOR]

Background: The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks.Methods: Adult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms).Discussion: Results from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes.Trial Registration: TRN: NCT01928758 , registered August 21, 2013. [ABSTRACT FROM AUTHOR]

Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and wellcontrolled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment. Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit. Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome. Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. Methods: The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. Results: Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p < 0.002). Conclusion: Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary. [ABSTRACT FROM AUTHOR]

Background: Chronic insomnia is among the most reported complaints of Veterans and military personnel referred for mental health services. It is highly comorbid with medical and psychiatric disorders, and is associated with significantly increased healthcare utilization and costs. Evidence-based psychotherapy, namely Cognitive Behavioral Therapy for Insomnia (CBTI), is an effective treatment and recommended over prescription sleep medications. While CBTI is part of a nationwide rollout in the Veterans Health Administration to train hundreds of providers, access to treatment is still limited for many Veterans due to limited treatment availability, low patient and provider knowledge about treatment options, and Veteran barriers such as distance and travel, work schedules, and childcare. Uptake of a briefer, more primary-care-friendly treatment into routine clinical care in Veterans Affairs (VA) primary care settings, where insomnia is typically first recognized and diagnosed, may effectively and efficiently increase access to effective insomnia interventions and help decrease the risks and burdens related to chronic insomnia., Methods: This hybrid type I trial is composed of two aims. The first preliminarily tests the clinical non-inferiority of Brief Behavioral Treatment for Insomnia (BBTI) versus the current "gold standard" treatment, CBTI. The second is a qualitative needs assessment, guided by the Consolidated Framework for Implementation Research (CFIR), to identify potential factors that may affect successful implementation and integration of behavioral treatments for insomnia in the primary care setting. To identify potential implementation factors, individual interviews are conducted with the Veterans who participate in the clinical trial, as well as VA primary care providers and nursing staff., Discussion: It is increasingly important to better understand barriers to, and facilitators of, implementing insomnia interventions in order to ensure that Veterans have the best access to care. Furthermore, it is important to evaluate the potential for new avenues of treatment delivery, like BBTI in the primary care setting, which can benefit Veterans who may not have adequate access to specialty mental health providers trained in CBTI., Trial Registration: ClinicalTrials.gov, ID: NCT02724800 . Registered on 31 March 2016.