bluuebunny/crossref_metadata_2025 huggingface dataset:
0328 The Natural History of Insomnia: High Sleep Reactivity Interacts with Greater Life Stress to Predict the Onset of Acute Insomnia
Authors: Walker Jamie , Vargas Ivan , Drake Christopher , Ellis Jason , Muench Alexandria , Perlis Michael
Published: May 2023

Introduction

Previous studies have shown that stressful life events are the primary trigger in the development of insomnia. One etiological model of insomnia suggests that sleep reactivity, or the vulnerability to stress-related sleep disturbance, may be an important moderator of this association. That is, some individuals have a predisposition to experience insomnia following acute stressors (i.e., sleep reactivity). The goal of the present study was to provide a proof of concept and, specifically, additional empirical evidence that the link between stressful life events and the onset of acute insomnia is moderated by sleep reactivity.

Methods

1,225 adults with a history of good sleep (Mage = 53.2 years, 68% female, 83% white) were recruited nationwide for an online study on sleep health. Participants completed surveys to assess sleep reactivity (baseline), sleep patterns (daily sleep diaries), and stressful life events (weekly survey). This high-density data (daily/weekly measures) allowed for a close examination of whether sleep reactivity predicts acute insomnia and how the association between stressful life events and sleep disturbance varies as a function of sleep reactivity. Due to the high variability of stressful life events and sleep over time, frequent data points were needed to test this etiological model of insomnia. Sleep diary data were used to identify sleep initiation/maintenance difficulties, including whether they met criteria for acute insomnia at any point during the one-year interval.

Results

Participants with high sleep reactivity, compared to low sleep reactivity, were at 76% increased odds of developing acute insomnia during the one-year interval. In general, greater weekly stressful life events were associated with greater insomnia during the subsequent week. Additionally, those participants with high sleep reactivity demonstrated a stronger relationship between weekly stressful life events and insomnia, such that they reported the greatest levels of insomnia following weeks where they experienced a greater number of stressful life events.

Conclusion

These results further support the sleep reactivity model of insomnia, and specifically, provide evidence that sleep reactivity predicts the incidence of acute insomnia in a sample of participants with no history of insomnia.

Support (if any)

Perlis: R01AG041783, K24AG055602; Vargas: K23HL141581, R25HL10544
0331 Effects of Cognitive Behavioral Therapy for Insomnia (CBTI) on Daytime Cognitive Functioning: A Report from the AIR Trial
Authors: Edinger Jack , Manber Rachel , Simmons Bryan , Johnson Rachel , Horberg Roxane , Depew Ann , Abraibesh Aysha , Eldridge-Smith E Devon , Strand Matt , Kushida Clete , Tsai Sheila
Published: May 2023

Introduction

Prior studies have shown that CBTI improves patient reported outcomes including daytime fatigue, mood status and quality of life, yet there are limited data concerning the effects of therapy on objective measures of daytime function. The current study tested the effects of CBTI on measures derived from the psychomotor vigilance test (PVT) in a sample of patients with comorbid insomnia disorder and sleep apnea.

Methods

Patients with insomnia and comorbid OSA, who were prescribed PAP therapy (N =155; Mage= 56.8±12.5 yrs.; 58.1% women) were randomized to digital CBTI (dCBTI) or Sleep Hygiene (CTRL). They completed PVT at baseline and after 8 weeks of treatment. Patients in the dCBTI arm who reached remission were offered no additional insomnia treatment, whereas those who did not were randomly assigned to 8 weeks of continued access to dCBTI or to a therapist delivered CBTI. Patients again completed the PVT after this second 8-week treatment phase. PVT outcome measures included mean reaction time, attentional lapses and efficiency scores. Linear mixed models were used to compare the PVT measures of patients receiving either of the CBTI treatment sequences with those assigned to the CTRL.

Results

Analyses showed significant group x time interactions for PVT attentional lapses (F = 3.04; p < .05) and for efficiency scores (F= 4.06; p< .025). Those who received either of the CBTI treatment sequences showed a greater reduction in attentional lapses and greater improvement in their efficiency scores from baseline to the post-treatment assessments than did those assigned the CTRL.

Conclusion

Findings indicate that CBTI improves objective indices of daytime cognitive functioning among those with comorbid apnea and insomnia disorder. Further tests of CBTI’s effects on these and other measures of cognitive functioning are warranted in other samples of insomnia patients who do and do not have medical, psychiatric and sleep disorder comorbidities.

Support (if any)

Funding support from the National Heart, Lung and Blood Institute, Grant # 1R01HL130559-01A1.
0333 INSOMNIA WITH OBJECTIVE SHORT SLEEP DURATION IS ASSOCIATED WITH INCIDENT CARDIOVASCULAR AND/OR CEREBROVASCULAR DISEASE
Authors: Karagkouni Efthalia , Fernandez-Mendoza Julio , He Fan , Bixler Edward , Karataraki Maria , Vgontzas Alexandros
Published: May 2023

Introduction

Insomnia with objective short sleep duration (ISSD) has been associated with adverse cardiometabolic outcomes, including hypertension and diabetes. However, data on the association between ISSD and the development of cardiovascular and/or cerebrovascular disease (CBVD) are limited. We aimed to examine whether ISSD is associated with incident CBVD.

Methods

1,211 men and women from the Penn State Adult Cohort (56.9% women, 51.82±12.85 years) without CBVD at baseline were followed up for 9.21±4.08 years. Based upon clinical history and physical examination, we defined the presence of CBVD as a history of diagnosis or treatment of heart disease and/or stroke. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year. Poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours sleep based on a 1-night, 8-hours, in-lab polysomnography. Logistic regression models examined the odds of incident CBVD, while simultaneously adjusting for race, sex, age, BMI, smoking, alcohol use, physical and mental health problems, sleep-disordered breathing and follow-up duration.

Results

Compared to normal sleepers with normal sleep duration, the highest risk of incident CBVD was in the ISSD group (OR=2.68, 95%CI=1.17-6.14), and the second highest in normal sleepers with short sleep duration (OR=1.65, 95%CI=1.10-2.49). The risk for incident CBVD was not significantly increased, in poor sleepers or those with insomnia with normal sleep duration (INSD).

Conclusion

Our findings indicate that the combination of short sleep duration with the complaint of chronic insomnia (ISSD) is associated with an additive effect on incident heart disease and stroke. These data add to the cumulative evidence supporting the existence of two insomnia phenotypes and that ISSD is the more severe biological phenotype of the disorder associated with physiologic hyperarousal and cardiovascular morbidity. The diagnostic and treatment implications of insomnia phenotyping based on objective sleep duration will be discussed.

Support (if any)
0334 INSOMNIA WITH OBJECTIVE SHORT SLEEP DURATION IS ASSOCIATED WITH METABOLIC SYNDROME
Authors: Karagkouni Efthalia , Fernandez-Mendoza Julio , He Fan , Bixler Edward , Karataraki Maria , Vgontzas Alexandros
Published: May 2023

Introduction

Several studies have shown that the insomnia with objective short sleep duration (ISSD) phenotype is associated with stage 2 hypertension and type 2 diabetes. We aimed to determine if there is an association between ISSD and metabolic syndrome (MetS).

Methods

We studied 1,741 adults from the Penn State Adult Cohort (age 20-88 years, 52.3% female, 12.4% racial/ethnic minority) who underwent a 1-night polysomnographic (PSG) evaluation, clinical history, and physical examination. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year, while poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours. MetS was defined by the presence of 3 or more of: BMI≥30 kg/m2, elevated total cholesterol (≥200 mg/dL), triglycerides (≥150 mg/dL), fasting glucose (≥100 mg/dL), or treatment, and blood pressure (≥130/85 mm Hg) or treatment. Logistic regression models examined the odds of developing MetS, while simultaneously adjusting for sex, race, age, alcohol, smoking, sleep-disordered breathing, mental and physical problems, and sampling weight.

Results

Compared to normal sleepers with normal sleep duration, ISSD was associated with a significantly increased risk of MetS (OR=2.04, 95%CI=1.13-3.70), while insomnia with normal sleep duration (INSD) was not (OR=1.03, 95%CI=0.53-1.99). Neither normal sleepers with short sleep duration nor poor sleeper with normal or short sleep duration were associated with increased risk of MetS. Further analysis of the clustering of the cardiometabolic risk factors revealed that in the ISSD group who had MetS, 94% had elevated blood pressure, 78% had elevated cholesterol, 72% had insulin resistance, 53% had elevated triglycerides, and 53% had BMI≥30 kg/m2.

Conclusion

These data indicate that hypercholesterolemia, but not hypertriglyceridemia or obesity, contributes to the association of ISSD with MetS. These data suggest that in addition to the previously-identified elevated blood pressure and insulin resistance, treatment of hypercholesterolemia in patients with ISSD may prevent the development of cardiovascular and cerebrovascular disease.

Support (if any)
0336 Tele-Self CBTi: Results of a Randomized Controlled Trial of a Nurse-Supported Self-Management Intervention for Insomnia Disorder
Authors: Ulmer Christi , Voils Corrine , Zervakis Jennifer , Goodwin Kaitlyn , Jeffreys Amy , Gentry Pamela , Rose Cynthia , Olsen Maren , Bosworth Hayden B
Published: May 2023

Introduction

Approximately half of all Veterans meet diagnostic criteria for Insomnia Disorder. Cognitive Behavioral Therapy for Insomnia (CBTi) is recommended as first-line treatment but access is limited. Self-help CBTi could increase patient access and is more effective with provider support. Self-help CBTi has not been evaluated in those with significant mental health morbidity or Veterans; a population having greater medical and mental health morbidity and more severe sleep difficulties than non-Veterans.

Methods

Treatment-seeking Veterans were randomly assigned to 6 sessions of Tele-Self CBTi or Health Education Control (HEC). Nurses without sleep medicine experience were trained to deliver Tele-Self CBTi; the combination of provider support plus professionally designed patient and provider CBTi treatment manuals developed through an iterative process integrating expert and patient feedback. Both arms received nurse phone contacts (≤20 minutes). Outcomes including insomnia severity, subjective and objective sleep parameters, fatigue and mood were assessed at baseline, post-treatment (8 weeks), and 6 months.

Results

Study participants (N=178) were 55 years of age (SD=13), mostly male (72%), with a mental health condition (83%), and about half African American (43%) and half Caucasian (49%). At post-treatment, Veterans randomized to Tele-Self CBTi realized greater reductions in insomnia severity (ISI estimated mean improvement 5.7 vs 2.0, p<.001) and greater improvements in fatigue and depression symptoms (ps<.04). At 6 months, ISI findings were sustained (5.3 vs. 2.4, p<.001) and more Tele-Self CBTi than HEC participants (32% vs 10%) scored below the cutoff suggestive of insomnia disorder (ISI< 11) (p=.001). Preliminary findings also suggest better post-treatment outcomes for Tele-Self CBTi on sleep diary SOL (25 vs 45 minutes) and WASO (34 vs 55 minutes).

Conclusion

A self-management CBTi requiring minimal provider resources was effective in reducing insomnia severity in veterans with considerable mental health co-morbidity. Tele-Self CBTi can help bridge the gap between unavailable resources and high demand for services and can serve as the entry level in stepped-care treatment for insomnia disorder. Future research is needed to identify characteristics of patients most likely to benefit from Tele-Self CBTi.

Support (if any)

Funding was provided by Veterans Affairs Office of Research and Development (CIN 13-410 and IIR 16-281).
0338 A Naturalistic within and between Subjects Comparison of the effects of Cannabis on Sleep among Young Adult, African Americans
Authors: Hurst Travan , Lavela Pewu , Sandhu Ishaan , Mellman Thomas
Published: May 2023

Introduction

Cannabis use is increasing, despite limited knowledge of its potential benefits and adverse effects. Reducing sleep disturbance appears to be a frequent motivation for nighttime cannabis use yet its effects on sleep are poorly documented. We leveraged data from an observational study of urban residing young adult African Americans where pre-bedtime cannabis use was variably endorsed with digital ecological momentary assessment (EMA) to conduct within and between subjects’ comparisons of sleep with and without preceding cannabis use.

Methods

Participant were recruited from an ongoing observational study that enrolls African Americans living in urban environments. 20 participants endorsed cannabis use on some but not all nights and were included in the within subjects’ comparison. 25 participants who used cannabis on 2 or more nights were compared with 28 participants who did not endorse prebedtime substance use. Total sleep time (TST), and wake after sleep onset WASO were derived from actigraphy monitoring; sleep quality (SQ) (scale: 1 “not at all rested”-10 “very rested”) and time in bed (TIB) were obtained from the EMA.

Results

While TST and WASO were very similar in both conditions and groups, within subjects’ SQ was superior on nights without cannabis (7.2 + 1.7 vs. 6.4 + 2.2, t=2.2, p=.04) and cannabis users spent more time in bed (minutes) than their non-cannabis using counterparts (447.6 + 77.1 vs. 373.6 + 66.1; t= 2.4, p=.04).

Conclusion

Among urban residing young African American adults, cannabis does not appear to improve sleep.

Support (if any)

This research was supported by the NIHLB grant R01HL136626 to Dr. Thomas A. Mellman.
0339 A phenomenological study on facilitators and barriers of Zero-time exercise in physically inactive adults with insomnia disorder
Authors: Chau Ching Sum , Yeung Wing Fai , Chen Shu Cheng , Lai Yuen Kwan , Lam Tai Hing
Published: May 2023

Introduction

Zero-time Exercise (ZTEx), a lifestyle-integrated exercise, might have beneficial effects on relieving insomnia. Exercise adherence is a key component for the success of exercise therapy. This study is to explore facilitators and barriers of Zero-time exercise adherence and the improvement in sleep quality in physically inactive adults with insomnia disorder.

Methods

The qualitative study used ten 1-hour focus group interviews (5 groups at immediately after training program, and groups at the end of 24-week study period) on improving sleep quality of 35 physically inactive adults with insomnia disorder who had enrolled in our previous randomized controlled trial, from Oct 2019 to Mar 2022. A framework approach with a semi-structured interview guide was used to reflect subjects' facilitators and barriers of adherence to Zero-time exercise. Different strategies were used to ensure the credibility, dependability, confirmability, and transferability of the study. Transcripts were analyzed using qualitative thematic content analysis. The interviews were audio-recorded and transcribed verbatim. In addition, the contents of each group were summarized into generalized descriptions using NVivo 11.0.

Results

35 physically inactive adults with insomnia disorder (female: 58.7%, mean age: 47.2 years). Four themes were identified: (1) perceived benefits or changes (e.g. perceived better sleep quality; perceived improved physical health and more energetic, and positive lifestyle changing), (2) facilitators to intervention delivery (e.g. the understanding of benefits of doing exercises and risks of not doing exercise, expectations of participants, monitoring and reminders provided in the study, and belief and responsibility of participation), (3) barriers to intervention delivery (e.g. difficulties in integrating exercises into daily live, physical health challenges faced by participants, limited improvement, and lack of support from people around) and (4) suggestions from participants (e.g. modifying the content of ZTEx to be more interesting; and providing more easily accessible exercise video).

Conclusion

Participants perceived benefits from the ZTEx intervention besides improving sleep quality. Participants’ compliance could be further enhanced if more assistance in helping them to integrate exercise into daily life. Social and familial support was also essential for their adherence.

Support (if any)

The study was supported by the Research Grants Council, General Research Fund, Hong Kong SAR (Project no.: 15100419)
0341 Acupuncture and Its Effects on Various Patterns of Insomnia
Authors: Tipaldo Kristen , Seixas Azizi , Chery Maurice , Bernard Maritza , Jean-Louis Girardin , Blanc Judite
Published: May 2023

Introduction

Acupuncture has been shown to treat Insomnia. Insomnia is classified as difficulty falling asleep and staying asleep, waking up throughout the night, and waking up early, which is associated with decreased daytime function, mental health, and cardiometabolic health. The purpose of our study is to describe a series of 12 cases seen in an Acupuncture Clinic in Tampa for symptoms of Insomnia.

Methods

We used intakes from eight females, seven Caucasians, one African American, and four Caucasian males aged 30-65 and assessed information through Acupuncture systems. Patients were seen for Insomnia along with other treatable symptoms between January 2019 and October 2022. Information on Gynecological, Orthopedic, Genito-Urinary, Psycho-Emotional, Gastrointestinal, Respiratory, Ear/Nose/Throat, Neurological, Endocrine, and Allergic/Immunologic were collected. Follow-up intake information and Subjective, Objective, Assessment Plan (SOAP) notes were conducted during each visit through the electronic medical system. Differential diagnosis, as well as ICD codes, are housed within the system. The Acupuncture method utilized was Traditional Chinese Medicine (TCM) and not dry needling, which does not include a differential diagnosis and is typically used for Orthopedic conditions.

Results

We retrieved data from twelve patients, eight women and four men receiving Acupuncture treatment in private practice. The mean age of the sample was 46.91 [30-65] years. Of the 12 patients, 10 of them fully recovered after treatment. Among those who fully recovered, treatments ranged as low as two up to 14, with three patients receiving six treatments and one receiving 14. One patient discontinued treatment after six treatments with a slight change to differential insomnia pattern. One patient received fourteen treatments with only partial remission to differential insomnia pattern.

Conclusion

Acupuncture may be an effective modality in treating Insomnia, regardless of the pattern. Further studies are necessary to determine the mechanism of action.

Support (if any)

R01HL152453, R01MD007716, and R01HL142066
0342 Are Clinical Trials for Insomnia Recruiting Real World Patients?
Authors: Golebiowski Raphael , Kolla Bhanuprakash , Mansukhani Meghna
Published: May 2023

Introduction

Studies that have resulted in recent approval of hypnotics for chronic insomnia disorder (CID) have extremely restrictive inclusion criteria. We sought to determine how many patients seen in a sleep medicine clinic would be eligible to participate in these trials in order to assess the generalizability of these findings to clinical populations.

Methods

Six-hundred and twenty-eight patients were screened to identify 100 patients who were ≥18 years old, had a diagnosis of CID, and were prescribed a hypnotic medication at a sleep medicine clinic in a quaternary level healthcare center. Information regarding age, sex, body mass index, comorbid diagnoses, sleep schedule, medications, alcohol/tobacco/illicit drug use, caffeine intake, as well as Epworth Sleepiness Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index scores were abstracted. These data were compared against the inclusion and exclusion criteria for recent regulatory Phase III trials of orexin receptor antagonists (suvorexant, lemborexant, daridorexant).

Results

Of the 100 patients with CID (mean age=56.2 years; 57% female), only 3 patients met eligibility criteria for inclusion. A majority of patients (80%) would have been excluded due to a prior/concurrent trial of cognitive behavioral therapy for insomnia. If this criterion was set aside, only 11 patients would have been eligible to participate. The remaining top reasons for potential exclusion from the regulatory trials were: presence of medical comorbidities (36%), daytime napping (33%), and sleep apnea (30%).

Conclusion

A very small number of patients with CID seen in a clinical setting met eligibility criteria for clinical trials of hypnotic medications resulting in regulatory approval. This substantially limits the generalizability of findings from these trials and restricts our ability to determine the efficacy of these drugs in clinical populations. Future trials should enroll patients with less restrictive criteria to help determine the effectiveness of these medications in real world settings.

Support (if any)
0343 Association between the real-world use of trazodone and daytime impairment in US patients with insomnia
Authors: Büsser Alexander , Olivieri Antonio , Grandner Michael , McCall William V
Published: May 2023

Introduction

Trazodone is approved for the treatment of depression and is used off-label to treat insomnia despite Clinical Practice Guidelines recommending against this use. The objective of this real-world retrospective study is to explore whether trazodone use is associated with improvements in daytime impairment in US patients with insomnia.

Methods

Information on insomnia patients aged ≥ 18 years prescribed trazodone as first-line treatment between October 2015 and March 2020 was retrieved from HealthVerity. Insurance claims data were extracted for each patient alongside physician notes in free-text form. From the claims, patient demographics and prescription information were extracted. An ontology analogous to the Insomnia Daytime Symptoms and Impact Questionnaire (IDSIQ) was designed with three domains (i.e., alert/cognition, mood and sleepiness). The 14 IDSIQ terms were extended to 109 terms to reflect physicians’ language. Daytime impairment symptom frequency occurring from 182 days before treatment to ~3 months (mean) during treatment was measured as annualized rates normalized by one year as the duration before and during treatment is different. Each symptom noted in a visit is counted once in a specific domain. Results were stratified by dose: trazodone < 150mg (typically used for off-label insomnia treatment) and trazodone ≥150mg (approved dose for depression treatment).

Results

1187 and 246 unique patients were identified on the < 150mg and ≥150 mg trazadone doses, respectively. For trazodone < 150mg, the annualized rate of daytime impairment symptoms before and during treatment was 139.4 and 147.5, respectively, with a statistically non-significant overall increase (6%, p=0.313) and statistically non-significant increases in each domain (alert/cognition: 4%,p=0.574; mood: 10%, p=0.173; sleepiness: 5%,p=0.401). For ≥150mg trazodone, the annualized rate of daytime impairment symptoms before and during treatment was 143.5 and 142.2, respectively, with a statistically non-significant overall decrease (1%,p=0.941), statistically non-significant decreases in the alert/cognition (19%,p=0.128) and sleepiness (5%,p=0.712) domains and statistically non-significant increase in the mood domain (14%,p=0.400).

Conclusion

Patients with insomnia prescribed trazodone show similar levels of daytime impairment before and during treatment. This study suggests that the use of trazodone in patients with insomnia is not associated with a decrease in daytime impairment.

Support (if any)

Idorsia Pharmaceuticals Ltd.
0344 Behavioral Treatment of Insomnia with Concurrent Nocturia
Authors: Tyagi Shachi , Clarkson Becky , Perera Subashan , Newell Kandy , Resnick Neil , Buysse Daniel
Published: May 2023

Introduction

Behavioral therapy has proved effective for insomnia in older adults. However, its efficacy has not been examined among those with nocturia (awakening to urinate) which is the most common cause of insomnia in this age group. Thus we assessed the impact of behavioral sleep treatment on sleep in older adults with nocturia.

Methods

Fifty-six community-dwelling older adults (mean age, 72±6 years; 64% women) with nocturia frequency ≥2 per night were randomized to receive Brief Behavioral Treatment for Insomnia (BBTI) or information-only control (IC). We determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by a 3-day voiding and sleep diary. Participants concurrently wore a single-channel, EEG device Z-machine® for objective in-home sleep assessment. Insomnia Severity Index (ISI) was used to assess insomnia symptoms.

Results

Participants had a mean nocturia frequency of 2.2±0.7/night at baseline. Time in bed (TIB) decreased by 42±76 minutes among the BBTI group, but total sleep time (TST) increased by 20±95. Significant differences ± standard error between BBTI and IC in pre- to post-intervention changes were observed for TIB (-41±18 minutes, p=.03) but not TST (27±18, p=.14). Compared to the IC group, the BBTI group also showed a greater improvement in ISI (-3.3±1.4, p=.02) as well as objectively measured sleep onset latency (-9.8±3.5, p=.008), latency to deep sleep (-19±11, p=.08), and percentage of total sleep time spent in deep sleep (8.4±3.1, p=.01). BBTI also decreased nocturia frequency to a greater extent (-0.49±0.20, p=.02)

Conclusion

BBTI improves insomnia symptoms, objective sleep measures, and nocturia in older adults with frequent sleep interruptions related to nocturia. Treatment for insomnia may be an important addition to current treatments for nocturia.

Support (if any)

NIA AG 060292
0345 BZRA Hypnotic Receptor Specificity and Ability to Discontinue Chronic Hypnotic Use
Authors: Roehrs Timothy , Koshorek Gail , Roth Thomas
Published: May 2023

Introduction

Clinicians prescribing hypnotics remain concerned regarding the inability to discontinue hypnotics after chronic use. In a controlled prospective study using self-administration choice procedures we tested whether BZRA hypnotic receptor specificity is predictive of discontinuation difficulty in a clinical trial in which insomnia subjects are instructed to stop taking their study medication after 6 months of nightly use.

Methods

DSM-V diagnosed insomnia subjects, aged 23-61 yrs, (n=41, 36 females), with no other sleep disorders, unstable medical or psychiatric diseases or drug dependency completed the trial. Following a screening polysomnogram and MSLT, participants were randomized to zolpidem XR 12.5 mg (n=16), eszopiclone 3 mg (n=11), or placebo (n=14) nightly for 6 months. After 6 months, nightly use, over a 2-week choice period, they were instructed to discontinue hypnotic use, but if necessary, to self-administer either 1, 2, or 3 capsules of their assigned “blinded” medication (zolpidem XR 6.25 mg, 6.25 mg, placebo; eszopiclone 2 mg, 1 mg, placebo as capsules 1, 2 and 3 respectively; or 3 placebos).

Results

Over the 14 nights 21 subjects took zero (51%) capsules; among the 20 taking capsules the median total number chosen over the two weeks was 3. Most took one capsule per night; 6 took > 1 capsule on a given night. Overall, the number of capsules taken declined from week 1 to 2 (p< .001). The eszopiclone group took a greater number of capsules than the placebo group (p<.005), with the zolpidem group between. The eszopiclone group also showed a trend (p<.07) to fail to reduce use from week 1 to 2.

Conclusion

The majority (51%) of the participants discontinued 6-month nightly hypnotic use and among those taking capsules the rate declined from week 1 to 2. The non-hypnotic receptor specific eszopiclone group took a greater number of capsules than the placebo group. This is the first ­demonstration of differential abuse liability among BzRA hypnotics.

Support (if any)

NIDA, grant#: R01DA038177 awarded to Dr. Roehrs.
0346 Cannabinol (CBN) effects in insomnia disorder: A randomised, double-blind, placebo-controlled, crossover, clinical trial protocol
Authors: Lavender Isobel , McGregor Iain , Sureav Anastasia , McCartney Danielle , Irwin Chris , Marshall Nathaniel , Gordon Chris , D'Rozario Angela , Saini Bandana , Grunstein Ron , Yee Brendon , Hoyos Camilla
Published: May 2023

Introduction

There is a clear need for novel interventions for insomnia disorder. Growing evidence suggests a role of the endogenous cannabinoid system in regulating circadian sleep-wake cycles, highlighting a potential avenue for novel therapeutics. Cannabinol (CBN), a trace cannabinoid formed through oxidation of delta-9-tetrahydrocannbinol (THC), is hypothesised to impact sleep. Despite anecdotal and ­preclinical evidence, the effects of CBN isolate on sleep have never examined through well-designed clinical trial procedures.

Methods

This randomised, double-blind, placebo-controlled, three-arm, crossover, single-site, pilot study will investigate the acute effects of oral dose CBN at 30 and 300 mg in twenty patients with clinician-diagnosed insomnia disorder (and Insomnia Severity Index [ISI] Score ≥15). Across three treatment sessions, each separated by two-weeks washout, participants will receive two doses of CBN and matched placebo, at random. Participants will undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioral function tests. The primary outcomes are CBN (30 and 300 mg) effects on sleep continuity (wake after sleep onset minutes), compared to placebo, measured using polysomnography.

Results

Secondary outcomes include changes to sleep micro-architecture, traditional sleep staging, and absolute spectral power during non-rapid eye movement sleep. Various other subjective and objective safety measures will be obtained.

Conclusion

This study will provide novel preliminary data on the effects of CBN on sleep and next-day function in adults living with insomnia disorder which will inform the design of larger clinical trials.

Support (if any)
0347 CBT-I Leads to Changes in Actigraphy and Sleep Diary-Assessed Sleep Parameters in Veterans with Psychosis and Insomnia
Authors: Klingaman Elizabeth , Howell Mary Katherine , Brown Clayton , Li Lan , Kreyenbuhl Julie , Taylor Maddison , Glieger Justine , Vivino Anthony
Published: May 2023

Introduction

Up to 80% of people with psychosis have insomnia. While insomnia worsens psychotic symptoms and functioning, treating insomnia may improve functioning and recovery. Cognitive Behavioral Therapy for Insomnia (CBT-I) is an effective treatment, but there is limited research on CBT-I in people living with psychosis. We developed guidelines and materials for conducting CBT-I with people with psychosis and evaluated actigraphy and sleep diary-measured outcomes in Veterans who participated in an RCT of CBT-I for psychosis.

Methods

Forty-seven Veterans with insomnia and psychosis were randomized to either CBT-I using novel psychosis-specific guidelines and materials (n=26) or to an active treatment control, the Health and Wellness (HW) intervention (n=21). Participants completed both actigraphy and daily sleep logs for two weeks at baseline, post-treatment, and 3-month follow-up.

Results

Using a mixed effects model for repeated measures, mean change from baseline at post and follow-up was compared for CBT-I for psychosis and HW. For actigraphy-measured total sleep time (TST) and time in bed (TIB), and diary-measured TIB, there was a significant decrease in these parameters for the CBT-I group relative to an increase for HW at post (t(1082)=-2.41, p=.016, d=-.38; t(1082)=-2.19, p=.029, d=-.44; t(1318)=-3.19, p=.002, d =-.70, respectively) and in diary-measured TIB at follow-up (t(1318)=-1.97, p=.049, d=-.37. Sleep diary-measured sleep efficiency (SE) increased significantly more in CBT-I than in HW (t(1266)=1.99, p=.047, d=.54) at post. There were no group differences in actigraphy-measured SE, sleep onset latency (SOL), or WASO, or sleep diary-measured TST, SOL, WASO, or number of awakenings at post. There were no other group differences for actigraphy- or diary-measured sleep variables at follow-up, though underpowered due to sample size at the follow-up timepoint.

Conclusion

Results indicate that CBT-I tailored to the needs of people with psychosis can change several actigraphy- and diary-assessed common sleep variables of interest--TST, TIB, and SE. CBT-I for psychosis should be further investigated with a larger randomized controlled trial over a longer time period.

Support (if any)

Time supported by U.S. Department of Veterans Affairs, RR&D-1IK2RX001836, PI: Elizabeth A. Klingaman.
0350 Daridorexant in patients with insomnia disorder: number needed to treat, number needed to harm & likelihood to be helped or harmed
Authors: Chalet François-Xavier , Luyet Pierre-Philippe , Rabasa Cristina , Vaillant Cédric , Saskin Paul , Ahuja Ajay , Citrome Leslie
Published: May 2023

Introduction

Patients with insomnia disorder have difficulty initiating or maintaining sleep and have impaired daytime functioning. Daridorexant is a dual orexin receptor antagonist approved for the treatment of insomnia. This analysis reports the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) with daridorexant 25 mg or 50 mg versus placebo over 3 months.

Methods

Phase 3 data from one of two pivotal trials (N=930: randomized 1:1:1 to daridorexant 25 mg, 50 mg, or placebo) were used to calculate NNT, NNH, and LHH. For the NNT analysis, wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, the Insomnia Daytime Symptoms and Impacts Questionnaire, and the Insomnia Severity Index were explored. NNT was assessed using a range of clinically meaningful thresholds (CMTs), from minimal clinical improvement (MiCI) to marked clinical improvement. NNH analysis was performed on adverse events (AEs) occurring in >1% of participants in any treatment arm. LHH values were calculated for all NNT outcomes using the NNH estimates for somnolence and fatigue AEs.

Results

At Month 1 and 3, NNT values at MiCI thresholds for daridorexant 50 mg ranged from 5–9 and 6–12, respectively, and were all statistically significantly different versus placebo, indicating a good therapeutic response. Daridorexant 50 mg had at least one NNT < 10 for CMTs across all outcomes. NNTs at MiCI thresholds for daridorexant 25 mg ranged between 7–328 and 8–1666. NNH values for daridorexant 25 and 50 mg were negative or not significantly different from placebo, confirming a good tolerability profile. For a somnolence AE, LHH values ranged from 83.3–200 for daridorexant 50 mg versus placebo. For a fatigue AE, LHH ranged from 4.3–10.2.

Conclusion

Daridorexant 25 mg and 50 mg both have a positive benefit-risk ratio compared with placebo over 3 months. Furthermore, daridorexant 50 mg showed ‘good’ NNT values (i.e. NNT < 10) over all efficacy endpoints in relation to the CMTs. NNH results confirmed the good tolerability profile of both doses.

Support (if any)

Funded by Idorsia Pharmaceutical Ltd.
0351 Differential Effect of Lemborexant and Zolpidem on Wake Across the Night in Patients with Insomnia Disorder
Authors: Roth Thomas , Cheng Jocelyn , Kumar Dinesh , Moline Margaret
Published: May 2023

Introduction

Insomnia can involve difficulty with falling and/or staying asleep; older adults tend to report more sleep maintenance issues. While zolpidem tartrate extended-release 6.25mg (ZOL) is indicated to treat sleep onset and maintenance, data indicate that ZOL may be less effective in the last 2 hours of the night. It is important to understand the differences between ZOL and lemborexant (LEM), a dual-orexin-receptor-antagonist with the same indication. In Study 304 (E2006-G000-304; NCT02783729), LEM treatment significantly improved objective sleep maintenance (wake after sleep onset [WASO] and WASO in the second half of the night) assessed by polysomnography (PSG) over 1 month compared with placebo (PBO) and ZOL in older adults with insomnia disorder. This post-hoc analysis assessed the effect of LEM and ZOL on wake at each hour (H) of an 8-h sleep period.

Methods

Study 304 was a randomized, double-blind, PBO- and active-controlled, parallel-group study in adults ≥55y. Subjects (n=1006) received PBO, LEM 5mg (LEM5) or 10mg (LEM10), or ZOL for 1 month. Wake (minutes) was assessed hourly from paired PSGs during single-blind PBO run-in and post-randomization at nights (NT) 1/2 and NT29/30. Change from baseline (CfB) for H1-8 was analyzed using pooled t-tests.

Results

Between-group baseline wake was similar. On NT1/2 and NT29/30, CfB for LEM10 was significantly greater (less wake) than PBO for all hours except H4 NT29/30. On NT1/2 and NT29/30, CfB for LEM5 was significantly greater than PBO for all hours except H4 NT1/2 and NT29/30 and H8 NT1/2. On NT1/2 and NT29/30, CfB for LEM5 and LEM10 were significantly greater than ZOL during H1,2,7, and 8. CfB for ZOL was not significantly different than PBO except for H2-6 NT1/2 and H3,5,6 NT29/30; CfB for PBO was significantly greater (better) than ZOL during H1 NT29/30.

Conclusion

LEM improves total sleep time by decreasing wake time throughout the night after sleep onset compared to PBO, and at the beginning/end of the night compared to ZOL. These findings support that ZOL may be less effective in maintaining sleep during the last 2 hours of the night compared with LEM in older subjects, especially those with sleep maintenance difficulties.

Support (if any)

Eisai Inc.
0352 Digital cognitive behavioral therapy in treating insomnia in older adulthood: A sub-analysis using individual participant data
Authors: Tarnai Kathryn , Henry Alasdair , Miller Christopher , Waxmonsky Jeanette , Emsley Richard , Espie Colin
Published: May 2023

Introduction

Insomnia prevalence increases across the lifespan with rates reported as high as 40% in the over 65 yo population. Although cognitive behavioral therapy (CBT) for insomnia is the first-line recommended treatment, low accessibility leaves many older adults with less effective treatment options including medication and sleep hygiene. Medication is not recommended due to side effects, which may be more probable in older individuals. Digital CBT (dCBT) for insomnia permits access to first-line treatment; however, little is known about its effectiveness in older adults. We evaluated the effects of fully-automated dCBT on symptoms of insomnia, anxiety, and depression in adults aged 65 and older.

Methods

Individual participant data from prior randomized controlled trials of dCBT for insomnia (Sleepio) were combined for those aged 65+ (range=65-92yo) with insomnia disorder (N=486). Participants received access to dCBT or a control. As the insomnia, anxiety, and depression outcomes were assessed differently across studies, scores were standardized into z-scores. Mixed-effects models estimated the effect of treatment on the combined sleep, depression and anxiety outcomes at post-treatment and follow-up. For studies using the SCI-8, chi-squared tests evaluated insomnia remission rates between groups at post-treatment.

Results

Digital CBT led to significantly greater improvements at post-treatment and follow-up relative to control for the combined sleep (ds≤-1.34, ps<.001) and depression (ds≤-0.35, ps≤.001) outcomes. For the combined anxiety outcome, dCBT led to significantly greater improvements at post-treatment (d=-0.30, p=.004). Those randomized to dCBT were more likely to achieve remission of insomnia (60% vs. 16%, p<.001) at post-treatment.

Conclusion

Fully-automated dCBT for insomnia is effective at improving symptoms of insomnia, anxiety, and depression in adults aged 65+. Digital CBT may therefore serve as a first-line treatment option for older adults with insomnia to improve sleep and broader mental health. Importantly, dCBT may serve as an accessible means for older adults to receive guideline concordant treatment at scale.

Support (if any)

This work was supported in part by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR, or Department of Health and Social Care.
0353 Effect of Lemborexant on Sleep Architecture in Adult and Elderly Subjects with Mild to Severe Obstructive Sleep Apnea
Authors: Zammit Gary , Cheng Jocelyn , Hall Nancy , Shah Dhara , Moline Margaret
Published: May 2023

Introduction

Lemborexant (LEM) is a dual-orexin-receptor antagonist approved to treat adults with insomnia. In such patients, LEM increased total sleep, with prominent increases in rapid eye movement (REM). Since patients with obstructive sleep apnea (OSA) may report sleep difficulties and show decreased REM sleep, sleep architecture was analyzed after treatment with LEM.

Methods

Studies 102 and 113 were double-blind, placebo (PBO)-controlled crossover studies in adult and elderly subjects with mild (apnea-hypopnea index [AHI] ≥5 to < 15) or moderate (AHI ≥15 to < 30)/severe (AHI ≥30) OSA, respectively, without insomnia. Subjects were randomized to LEM 10mg (LEM10) or PBO in two 8-night treatment periods (separated by ≥14 days). Least-squares-mean (LSM) for each sleep stage (minutes) was compared across conditions on Days 1 (D1) and 8 (D8). Treatment-emergent adverse events (TEAEs) were recorded.

Results

The analysis set comprised 39 subjects with mild OSA and 33 with moderate/severe OSA. On both days, total sleep time was significantly higher in the LEM condition in subjects with mild (D1: LEM10, 434.08; PBO, 385.46; P< 0.0001; D8: LEM10, 415.90; PBO, 386.85; P=0.003) and moderate/severe (D1: LEM10, 423.10; PBO, 385.48; P< 0.0001; D8: LEM10, 416.96; PBO, 385.57; P=0.001) OSA. Compared with PBO, total non-REM sleep significantly increased only on D1 in subjects with mild OSA (D1: LEM10, 330.57; PBO, 308.55; P=0.001; D8: LEM10, 323.77; PBO, 308.97; P=0.060) but on both days in subjects with moderate/severe OSA (D1: LEM10, 343.23; PBO, 327.45; P=0.006; D8: LEM10, 341.83; PBO, 322.48; P=0.018). Total REM sleep significantly increased in subjects with mild (D1: LEM10, 103.59; PBO, 76.91; P< 0.0001; D8: LEM10, 92.13; PBO, 77.93; P=0.004) and moderate/severe (D1: LEM10, 79.87; PBO, 58.03; P< 0.0001; D8: LEM10, 75.13; PBO, 62.69; P=0.006) OSA. REM latency was significantly decreased on both days in subjects with mild OSA (D1: LEM10, 51.96; PBO, 83.36; P< 0.0001; Day 8: LEM10, 67.52; PBO, 102.34; P=0.005) and only on D1 in subjects with moderate/severe OSA (D1: LEM10, 72.13; PBO, 98.90; P=0.029; D8: LEM10, 90.42; PBO, 106.63; P=0.242). LEM was well-tolerated; most TEAEs were mild.

Conclusion

In OSA subjects without insomnia, LEM nevertheless increased total sleep, non-REM, and REM sleep versus PBO.

Support (if any)

Eisai Inc.
0357 Pimavanserin 34mg at Bedtime for Insomnia in Veterans with Post-traumatic Stress Disorder: Open-label Case Series
Authors: Jones Melissa , Agrawal Ritwick , Sharafkhaneh Amir , Elammari Mohamed , Zhao Zhifang , Jorge Ricardo , Marsh Laura
Published: May 2023

Introduction

There is a critical need for effective and feasible interventions to address insomnia associated with post-traumatic stress disorder (PTSD). Several lines of evidence suggest that pimavanserin, a 5-HT2A inverse agonist approved by the FDA for the treatment of Parkinson's disease psychosis, may benefit PTSD-related sleep disturbances. We conducted a pilot, open-label study of pimavanserin 34mg at bedtime for the treatment of PTSD-associated insomnia to preliminarily assess the feasibility of this intervention and tolerability of our protocol (NCT04188392).

Methods

Adult, male and female Veterans with chronic insomnia disorder and PTSD received fixed dose, open label pimavansern 34mg at bedtime for 6 weeks. Subjects completed 7 days of actigraphy monitoring and two consecutive in-lab polysomnograms (PSGs) pre-treatment. Safety and adherence were assessed in-person at weeks 3 and 6 and otherwise weekly via telephone. Actigraphy monitoring and a closeout PSG were repeated at week 6. Primary outcomes were recruitment and retention rates, defined as the total number of subjects recruited into treatment (goal n=6) and treatment completion rates (goal 75%), respectively.

Results

A total of 6 subjects (mean age 35.3 [S.D. 6.3] years, 2 [33.3%] female, 2 (33.3%] black or African American, 2 [33.3%] Hispanic, 4 [66.7%] comorbid depression) were recruited over 5.8 months. One subject was found to have mild OSA (AHI 5.6). Insomnia Severity Index (ISI) scores were in the severe range for 4 of 6 [66.7%] subjects. All subjects (100%) completed treatment. There were no serious adverse events or medication discontinuations due to adverse events. Preliminary analyses revealed a greater tend toward improvement on subjective measures of insomnia compared to objective sleep measures.

Conclusion

This open-label case series provides preliminary evidence for the tolerability of pimavanserin in Veterans with PTSD-associated insomnia and feasibility of our protocol. A larger, randomized controlled trial is needed to detect a meaningful clinical difference in insomnia severity following treatment with pimavanserin.

Support (if any)

Michael E. DeBakey VA Medical Center Seed & Bridge Award; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine