Abstract Introduction Hypersomnolence, defined as excessive daytime sleepiness with normal or prolonged sleep duration, is a common problem encountered in sleep medicine. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision categorizes unexplained hypersomnolence as hypersomnolence disorder (HD). The Hypersomnia Severity Index (HSI) was developed to assess the severity and impairment of hypersomnolence, yet no previous validation has been performed in patients experiencing unexplained hypersomnolence. As such, this investigation systematically examined the HSI's psychometric properties in a clinical sample of unexplained HD. Methods Archival data from unmedicated research participants and clinic patients (n = 179; average age = 27.8 ± 6.99 years; percent female = 77.7 %) were utilized for this validation. A comprehensive analysis of psychometric properties was performed to assess the validity (factorial, construct, and criterion) and reliability (internal consistency and test-retest) of the HSI. Receiver operating characteristic (ROC) analysis was utilized to identify a threshold that differentiated HD from non-HD participants. Results The HSI demonstrated strong psychometric properties. Internal consistency was excellent (Cronbach’s α = 0.92), with item-total correlations satisfactory across all items. Factor analysis confirmed a two-factor structure. Convergent and concurrent validity were evidenced by significant associations between the HSI and established measures of hypersomnolence (r = -0.63 to 0.84; r = -0.26 to 0.35). Discriminant validity was supported by weak or nonsignificant correlations with unrelated constructs (r = 0.15 to 0.25). Test-retest reliability over a one-year period was strong (r = 0.89), and a cutoff of ≥ 15 best differentiated HD from non-HD participants. Conclusion This investigation demonstrates the validity and reliability of the HSI in HD. While additional research is warranted, our findings support the use of this instrument in HD for both clinical and research purposes. Ultimately, the use of a validated instrument in HD will advance research in this important but understudied area of sleep disorders. Support (if any) This study was supported by grants from the American Sleep Medicine Foundation (138-SR-16 and 229 SR-20), National Institute for Nursing Research (R21NR018288), and National Institute of Mental Health (K23MH099234).

Background: Sleep disturbance is common in patients receiving hematopoietic stem cell transplantation (HCT). Mindfulness-based interventions (MBIs) can improve sleep quality during and following cancer treatment by reducing treatment-related symptoms and enhancing immune function. Methods: We conducted a randomized controlled pilot study investigating the feasibility of implementing Mindfulness Awareness Practices for Insomnia (MAP-I) in patients with multiple myeloma (MM) undergoing autologous HCT. Patients were randomized to receive either MAP-I or a Sleep Health Education (SHE) intervention, both consisting of six videos viewed pre-HCT and three virtual sessions in the two weeks post-HCT. Feasibility was assessed by meeting an enrollment rate of 35% and a retention rate of 85%. Results: We screened 120 patients; 54 (45%) were deemed ineligible and 42 (35%) declined participation. Twenty-four of the 66 eligible patients approached were enrolled into the study (36.4% enrollment rate) and were randomized to either MAP-I or SHE. Seven patients completed the study (29.2% retention rate). Most participants who withdrew consent cited feeling overwhelmed or too sick to continue post-HCT. Amendments were iteratively implemented to increase enrollment and retention rates including addition of a study incentive, modifications to the video timeline, and earlier introduction of the mindfulness instructor. Conclusion: Study results detail challenges and opportunities in retaining patients with MM in a virtual MBI sleep intervention during the peri-transplant period. While enrollment met feasibility criteria, most patients felt too overwhelmed or sick in the peri-transplant period to complete the intervention and associated study tasks. Future research should investigate MBIs at other time points throughout HCT. Trial registration: NCT04271930, 2/17/2020.

Evaluate nocturnal polysomnography sleep stage stability features in an adult, sample of clinical patients with hypersomnolence disorder (HD) against healthy sleeper controls (HSCs). Explore differences in sleep stage stability features across HD who displayed objective criteria for idiopathic hypersomnia (IH) (HD/IH+) and those who did not (HD/IH−). Sixty unmedicated clinical patients with HD (average age = 28.6 ± 8.6 years; percentage female = 78.3

Abstract Introduction Hypersomnolence disorder (HD) is characterized by excessive daytime sleepiness of undetermined etiology. HD is poorly understood with no established biomarkers. Slow waves during non-rapid eye movement (NREM) sleep are associated with the restorative aspects of sleep. Since nonrestorative sleep is a core feature of HD, it is hypothesized that alterations in sleep slow waves may be an HD feature. Thus, this investigation was designed to evaluate slow wave activity (SWA) and characteristics (SWC) in HD, relative to healthy sleeper controls (HSC). Methods 60 unmedicated clinical patients meeting criteria for HD were compared against 29 HSC. All participants underwent polysomnography (PSG) and multiple sleep latency testing (MSLT) at Wisconsin Sleep, with other subjective and objective measures also collected. All-night, six-channel electroencephalography (EEG) data from ad libitum, nocturnal PSG were processed using a validated automatic protocol followed by manual inspection. For each channel of artifact-free EEG from NREM staged epochs, normalized SWA (1-4.5hz) and SWC (incidence, pre-slope, post-slope, and peak amplitude) were calculated in accordance with previously utilized methodology. Post-hoc analyses evaluated slow wave characteristic differences between low- and high-amplitude (≥40μV) slow waves. Linear regression compared groups across normalized SWA and SWC, with adjusted models accounting for relevant, available covariates. Results HD participants were young- to middle-aged (mean age = 28.6 ± 8.6) and predominantly female (percentage female = 78.3%), and HSC were comparable. HD participants displayed significantly reduced SWA across all channels, with effects most pronounced frontally and centrally, and greater in the left relative to right hemispheres. HD participants displayed significant alterations across all SWC, with generally consistent patterns of reductions in incidence, amplitude, and slope across frontal and central EEG derivations. SWC alterations varied significantly by both brain region and low- versus high-amplitude waves. Conclusion This study demonstrates and expands on a growing evidence base that alterations in slow waves may be a core feature of HD. Targeted studies that manipulate NREM slow waves in disorders of unexplained hypersomnolence, including modification of incidence and morphology varied by brain region and hemisphere, are required to clarify whether alterations in slow waves are causal to symptoms of hypersomnolence. Support (if any) AASM Foundation (138-SR-16) and NINR (R21NR018288)

Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplant (HCT) and is associated with morbidity and high symptom burden. This study evaluated two biobehavioral mechanisms, inflammation and circadian rest-activity rhythms, that may underly commonly reported psychological and physical symptoms in cGVHD patients. Adults with cGVHD (N=57) wore a wrist actigraph for 7 days, provided a blood sample, and completed patient-reported outcome (PRO) measures. 24-hour rest-activity indices were derived from actigraphy. Cytokines and chemokines relevant to cGVHD were measured in peripheral blood plasma using multi-analyte immunoassays. Multiple regression evaluated the extent to which rest-activity indices and inflammatory biomarkers predicted PROs. Higher levels of circulating IL-8 and MIP-1α were associated with worse depression (β = 0.35, p = 0.01; β = 0.33, p = 0.02) and sexual function (β = -0.41, p = 0.01; β = -0.32, p = 0.03). MIP-1α was associated with more severe insomnia (β = 0.36, p = 0.01). Higher circulating MIF was associated with more severe anxiety (β = 0.28, p = 0.048) and fatigue (β = 0.35, p = 0.02). Il-6, TNFα, and MCP-1 showed few associations with PROs. There were few associations between actigraphy indices and PROs; however, participants with a later daily activity peak (acrophase) reported poorer sexual function (β = -0.31, p = 0.04). Models covarying for age, cGVHD severity, and time since HCT yielded a similar pattern of results. Results suggest that pro-inflammatory cytokines and chemokines associated with cGVHD may contribute to PROs, identifying a biobehavioral mechanism that may be a useful target for future interventions.

Objective Endometrial cancer survivors experience persistent health-related quality of life concerns, including pain, fatigue, and disrupted emotional and social functioning. The purpose of this longitudinal study was to evaluate associations between biobehavioral factors, including daytime physical activity, nighttime sleep, and 24-h circadian rest-activity rhythms, with psychological and physical symptoms following endometrial cancer surgery. Methods This study included 69 adult female patients undergoing surgery for endometrial cancer. At each of three assessment points (1, 4, and 16 weeks post-surgery), participants wore a wrist actigraph for 3 days and completed a sleep log and self-report measures of depression and anxiety (Inventory of Depression and Anxiety Symptoms), pain (Brief Pain Inventory), fatigue (Fatigue Symptom Inventory), and insomnia (Insomnia Severity Index). Physical activity, sleep, and 24-h rest-activity indices were derived from actigraphy. Mixed- and fixed-effects linear regression models were utilized to evaluate relationships between actigraphy indices and patient-reported outcomes. Results Clinically elevated fatigue persisted for a majority of participants (64 %), while a sizeable minority continued to report clinically elevated insomnia (41 %) and pain (19 %) at 16-weeks post-surgery. Participants who recorded less daytime activity, more disrupted sleep, and less consistent 24-h rest-activity rhythms by actigraphy reported more depression and anxiety symptoms and greater pain and fatigue. Within individual participants, at time points when activity was lowest, sleep most disrupted, and 24-h rest-activity rhythms least consistent, participants experienced more psychological and physical symptoms. Conclusions Findings suggest that disruptions in daytime physical activity, nighttime sleep, and 24-h rest-activity patterns contribute to patient-reported outcomes in the weeks and months after endometrial cancer treatment. Findings support modifiable intervention targets to address co-occurring physical and psychological symptoms and optimize health and recovery after endometrial cancer surgery.

Women have increased risks for both sleep disturbances and disorders and for mental health issues throughout their lives, starting in adolescence. Women have a higher prevalence of insomnia disorder and restless legs syndrome (RLS) versus men, and obstructive sleep apnea (OSA) is more likely as women age. Hormonal transitions are important to consider in women's sleep. For women, insomnia, OSA, and RLS are predictive of depression, and insomnia and sleep-disordered breathing are predictive of Alzheimer disease. These findings underscore the importance of assessment, treatment, and future research examining sleep and mental health in women, given their unique and increased vulnerability.

Purpose Chronic graft-versus-host disease (cGVHD) is a common late complication of allogeneic hematopoietic cell transplantation (HCT). This study comprehensively evaluated physical and psychological function among individuals with cGVHD. Additional aims were to investigate relationships between disease severity and psychological and physical function, and to investigate patterns of psychological and physical function by disease site. Method Adults at least 6 months post allogeneic HCT were enrolled and either had cGVHD ( n =59) or served as a reference sample of HCT survivors with no cGVHD history ( n = 19). Participants completed self-report measures of depression, anxiety, fatigue, insomnia, pain, cognition, and sexual function and had a comprehensive clinical evaluation of cGVHD using NIH consensus scoring criteria. Participants with cGVHD were stratified by disease severity and site and compared to the reference group with no cGVHD. Results Participants with mild cGVHD had comparable psychological and physical symptoms to the reference sample, while participants with moderate cGVHD experienced more severe anxiety and problems with sexual function, and participants with severe cGVHD experienced more severe depressive symptoms and pain compared to the reference sample. Participants with cGVHD manifesting in the skin and GI tract had the most severe symptoms, including mood disturbance, fatigue, and pain. Conclusions and Implications for Cancer Survivors Results suggest that patients with more severe cGVHD and those with cGVHD manifesting in the skin, GI tract, and lungs are at risk for poorer psychological and physical outcomes and may benefit from proactive interventions to optimize function.

This study evaluated the accuracy of the algorithmic oxygen saturation (SpO2) nadir detection of WatchPAT (Zoll/Itamar, Caesarea, Israel) compared with visual inspection in a real-world setting. SpO2 tracings for 209 consecutive adult WatchPAT recordings were reviewed for SpO2 artifact, with erroneous SpO2 data removed manually. Error rates for SpO2 minima were determined across all studies, and relationships between correct and erroneous studies examined. The overall error rate for SpO2 nadir was 22.5

Abstract Introduction Performance of split-night polysomnography, the application and titration of positive airway pressure (PAP) therapy after an initial diagnostic interval, is a common practice in clinical sleep medicine. There is no currently recommended apnea-hypopnea index (AHI) threshold at which PAP should be applied during polysomnography. Differences in American Academy of Sleep Medicine (AASM) and Centers for Medicare and Medicaid Services (CMS) hypopnea scoring criteria and limitations on real-time hypopnea classification complicates identification of an optimal split-night threshold. Of particular concern is that patients may be “split” under AASM hypopnea rules but have insufficiently severe sleep disordered breathing under CMS rules to be diagnosed or treated appropriately. This study aimed to clarify optimal AHI thresholds for split night polysomnography in the context of a laboratory-wide transition from CMS to AASM hypopnea scoring criteria. Methods Effective October 1, 2021, our laboratory transitioned solely to scoring AASM-defined hypopneas, with additional post hoc identification of CMS hypopneas for reporting purposes. With this change, the split-night threshold was changed from 15 to 30/hr. All diagnostic polysomnograms (without PAP therapy) performed on adult patients through October 31, 2022, were retrospectively analyzed to clarify the effect of changing hypopnea scoring criteria in this context. Results 634 diagnostic polysomnograms were analyzed. An AHI threshold of 15/hr (using AASM hypopnea criteria) in the first two hours of sleep with at least 3 hours of time remaining for PAP titration would have resulted in 96 additional patients receiving treatment with PAP therapy. Among these, only one (1.04%) had CMS AHI below 5/hr. Sixty-eight of these patients had CMS AHI 5-15/hr during the first two hours of sleep. Among these, only eight patients did not have an additional comorbidity or symptom profile under CMS guidelines making them eligible for PAP therapy, however, none had CMS AHI >15/hr when the full night of sleep was analyzed. Conclusion Our study suggests there is little need to raise the split-night threshold when transitioning from CMS to AASM hypopnea criteria, and doing so substantially reduces the number of patients treated with PAP therapy in the sleep laboratory. Support (if any) None

Background: Insomnia, fatigue, and depression are among the most persistent and distressing concerns for hematologic cancer patients recovering from hematopoietic cell transplantation (HCT). This study will evaluate a novel behavioral intervention, Restoring Sleep and Energy after Transplant (ReSET), designed to alleviate insomnia, fatigue, and depression by improving rest-activity patterns. Evidence-based behavioral strategies to improve nighttime sleep and increase non-sedentary daytime activity will be combined to optimize 24-h rest-activity patterns. Methods: The protocol herein evaluates the feasibility and acceptability of ReSET by conducting a pilot randomized controlled trial to compare the intervention with usual care. Adults undergoing HCT will be randomly assigned to ReSET or usual care. The ReSET arm will receive 3 face-to-face sessions and telephone coaching delivered in an individual format tailored to each patient. Patient-reported insomnia, fatigue, and depression will be the primary outcome measures. Actigraphy will be used to objectively quantify rest-activity patterns. Semi-structured interviews will evaluate participant satisfaction with ReSET. The goals are to determine: (1) participant satisfaction with and acceptability of the behavioral techniques; (2) facilitator fidelity and participant uptake of key intervention components; (3) ability to recruit, retain, and collect complete data from participants; (4) participant willingness to be randomized and acceptability of the control condition; and (5) validity and acceptability of the assessment strategy. Conclusion: The overarching goal is to optimize recovery following HCT with a brief, non-invasive intervention that can be implemented as a part of routine clinical care.

Abstract Introduction Sleep state misperception, or paradoxical insomnia, is a condition whereby an individual reports being awake even though polysomnographic evidence confirms they were asleep. Normally, an indication of sleep state misperception is determined by asking a patient to estimate the amount of wakefulness experienced after a full night of laboratory-monitored sleep. While clinically useful, this crude, post-hoc assessment does little to inform the neurobiological underpinnings of sleep state misperception. Here we used serial awakenings to exploit instances where a direct confirmation of sleep was followed by a subjective report of wakefulness. Methods 256 channel EEG with EMG, EOG and ECG was recorded in 19 primary insomnia (PI) subjects and 19 age- and sex-matched good sleeping controls (GSC) after a baseline sleep night ruled out comorbid disorders. After periods of stable sleep, participants were probed every 30 seconds with increasing intensity tones until a full awakening was achieved. Subjects were then asked to report whether they were awake or asleep before hearing the sound before going back to sleep. EEG data prior to the awakening was examined using multi-taper spectral analysis. Results Out of 464 serial awakenings (average 12 per subject, range 4-16), roughly 10% resulted in subjective wake reports during sleep (35 in NREM, 11 in REM; 24 in PI, 22 in GSC). Many of these occurrences included obvious arousals or other signs of wakefulness prior to the awakening tone. Altogether, 8 clean wake reports (4 in PI), occurred during stage N2 or N3 that could be matched with similarly clean data when the same subject reporting being asleep. Interestingly, spectral analysis of the 10 seconds prior to the awakening revealed significantly more alpha activity (9.1-11.3Hz paired t-test, p < .05) but no significant difference in slow wave activity. The alpha increase was localized to a mid-central region, similar to the alpha difference seen previously during deep sleep between PI and GSC groups, but also extended frontally. Conclusion Sleep state misperception may result from a localized increase in alpha activity while sleep persists. Serial awakenings are a useful tool for examining this paradoxical state. Support (If Any) Funded by the MERCK Sharp and Dohme Corporation.

Back to table of contents previous chapternext chapter No AccessChapter 16.Sleep and Circadian Rhythm Sleep-Wake DisordersEdited by:https://doi.org/10.1176/appi.books.9781615375196.ds16AboutSectionsView chapterExcerptView Full Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View chapterSectionsNormal Age-Related Changes | Sleep Disorders | Psychiatric and Medical Comorbidities | Medications | Behaviors | Assessment | Treatment | Conclusion | ReferencesExcerptMore than half of persons age 65 years and older report some type of sleep disturbance (Foley et al. 1995), and sleep disturbance is associated with increased risk of significant health consequences in older adults such as increased emergency department use, hospitalization, falls, nursing home placement, and mortality (Spira et al. 2012; Stone et al. 2008; Tzuang et al. 2021; Wallace et al. 2019). Unfortunately, a widespread misconception is that increased sleep disturbance is a normal function of aging. Although some normative changes in sleep are related to aging (Ohayon et al. 2004), sleep disturbance in older adults is not normative and is more likely to occur when common medical and psychiatric issues are present (Foley et al. 1995). Moreover, historically, sleep disturbance has been considered a secondary symptom of medical and psychiatric issues (e.g., chronic pain, depression). However, epidemiological data have supported a comorbid model in which sleep disturbance and medical and psychiatric issues have bidirectional relationships (Afolalu et al. 2018; Bao et al. 2017; Finan et al. 2013). This model supports the idea that all issues may warrant clinical attention, including the often-ignored issue of sleep disturbance. Thus, sleep disturbance is a key area to consider within geriatric psychiatry. In this chapter, we review normative age-related changes in sleep and the most common sleep disorders, medical and psychiatric comorbidities, medications and substances, and psychosocial stressors associated with sleep disturbance in older adults (Table 16–1). We also consider sleep assessment and treatment approaches in older adults. Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone The American Psychiatric Association Publishing Textbook of Geriatric Psychiatry Information©American Psychiatric Association Publishing History Published online 8 January 2023 Published in print 9 August 2022

Obstructive sleep apnea (OSA) is common in geriatric patients and has been associated with neurocognitive disorders such as Alzheimer's disease and other dementias. Dexter and Ebert (2019) reported a unique pattern of lower scores for immediate memory relative to delayed memory was observed in patients with OSA on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The aim of the current investigation was to examine the frequency of confirmed OSA diagnosis in persons with snoring and immediate memory scores less than delayed memory scores in ambulatory geriatric patients referred for memory assessment.Patients were initially assessed for memory complaints at the University of Wisconsin-Madison Geriatric Memory Assessment Clinic (2016 -2020). All patients completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Randolph, 1998, 2012) as part of a multidisciplinary evaluation. Patients were referred for a sleep evaluation if sleep disordered breathing was reported and the score difference was noted with immediate memory being less than delayed memory on RBANS. Sleep evaluations consisted of either home sleep testing or polysomnography, based on clinical indication. Board-certified sleep medicine physicians interpreted all sleep studies, and graded the severity of OSA as mild, moderate, or severe.Results are depicted in Table 1. There were 251 patients referred for sleep evaluation (mean age 75.5 years). Of these, 158 patients completed sleep testing (93 males; 65 females), of which 127 (80.4%) were ultimately diagnosed with OSA. Among sleep study completers, 72 (57%) had moderate or worse sleep apnea. The proportion of cases with moderate or worse sleep apnea was similar for male (59%) and female (53%) completers.This retrospective investigation involved geriatric memory clinic patients with RBANS scores that were lower in immediate memory compared to delayed memory and evidence of snoring that resulted in a referral for a sleep study. The finding of OSA in 80% of the patients evaluated, and the comparable results of male and female patients suggests that all patients who snore and have this unique RBANS profile should be assessed for OSA.

Introduction Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need. Methods We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome. Results All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation. Conclusions The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores.

Objective/Background: Dysfunctional sleep-related cognitions (SRCs) have been demonstrated in both insomnia and depression, but have not been evaluated in patients experiencing depression with co-occurring hypersomnolence. Given the prominence of maladaptive thinking in depression with comorbid insomnia, dysfunctional SRCs may also exist in depressed persons experiencing hypersomnolence. Identifying potentially maladaptive SRCs may assist development of cognitive-behavioral strategies to alleviate hypersomnolence and its related impairment, particularly when comorbid with depression. Participants: Twenty-two unmedicated persons with major depressive disorder (MDD) with comorbid hypersomnolence (MDD+/HYP+), as well as age- and sex-matched persons with MDD without hypersomnolence (MDD+/HYP-) and healthy controls (HC). Methods: Participants completed the Dysfunctional Beliefs and Attitudes About Sleep-16-item (DBAS-16) and underwent overnight polysomnography. Groups were compared across clinical and sleep domains, as well as DBAS-16 global, subscale, and individual item scores. Additional analyses evaluated DBAS-16 components while controlling for depression severity. Results: Groups significantly differed across all collected sleep and mood metrics consistent with diagnostic classification. MDD+/HYP+ DBAS-16 global score was significantly elevated, relative to HC, and was comparable to MDD+/HYP-. A DBAS-16 global score significant group effect was maintained while controlling for depression symptom severity, however only individual DBAS-16 items related to quantity and quality of sleep demonstrated particular relevance to MDD+/HYP+ compared to other groups. Conclusions: Results suggest potentially maladaptive SRCs in MDD+/HYP+. Further efforts are needed to clarify whether these beliefs and attitudes about sleep in persons with hypersomnolence are in fact dysfunctional, as well as identify relevant content for development of a novel hypersomnolence-related SRC metric.

Objectives Information is lacking regarding how commonly unblinding of treatment assignment occurs in hypnotic randomized clinic trials (RCTs). We now report the "best guesses" of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). Methods REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors. At the conclusion of study participation, 89 of the participants in this study, the study coordinators, and the study physicians each independently recorded their "best guess" of the treatment assigned. Results Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time, and none were different from chance alone. Agreement between patient/coordinator, patient/doctor, and coordinator/doctor dyads were 75%-78% with no significant differences in agreement between the dyads. Conclusions "Best guesses" of all parties were not different from chance, suggesting that the blind was maintained and that assessment bias was minimized in this RCT of zolpidem ER versus placebo. Our results may not apply to other hypnotics or other RCT designs.

Abstract Introduction Some hypnotic medications have obvious subjective effects, including therapeutic effects (i.e., anti-insomnia effects), and side effects (i.e., feelings of impairment/intoxication). Information is lacking regarding whether the subjective effects of hypnotics result in unblinding of treatment assignment (active drug versus placebo) in hypnotic randomized clinic trials (RCTs), thus undermining internal validity of study results. In response, we now report the ‘best guesses’ of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). Methods Eighty-nine of the 103 participants in the REST-IT study completed their ‘best guess’ regarding which randomized treatment they had been assigned. REST-IT was a blinded RCT, comparing zolpidem controlled release (CR) versus placebo at bedtime given over 8 weeks in adults with major depressive disorder who also had insomnia and suicidal ideation, and who also received open label fluoxetine. At the conclusion of study participation, the study participants, the study coordinators and the study physician each independently recorded their ‘best guess’ regarding which treatment arm the patient had been assigned. The study physicians and the study coordinators had access to the participants’ Insomnia Severity Index scores when the ‘best guess’ was made. Results Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time. The percentage guessed correctly did not differ significantly between groups. Physicians most often guessed placebo (56.2%) while study coordinators most often guessed zolpidem-CR (55.1%). Agreement between pairs of study participants with the study coordinators and the study physician was moderately high, with all kappa values 0.49- 0.57, and all kappa differences between zolpidem and placebo with p-values >0.8. Conclusion The blind was maintained in this RCT of zolpidem-CR versus placebo, especially for the physicians. Our results may not apply to other hypnotics or other RCT designs. Support NIMH MH095776, MH095780, MH95778