Comorbid Insomnia Research Articles

0839 Does CBT-I Dose Improve Depression and Anxiety in Patients Diagnosed with Breast and Prostate Cancer?

Abstract Introduction It has been widely reported in the literature that insomnia, depression, and anxiety are reciprocally related, and that CBT-I not only improves insomnia but also symptoms of depression and anxiety. With respect to cancer, patients of-ten report high co-morbidity of insomnia, fatigue, depression, and anxiety, with fatigue occurring in almost all patients diagnosed with cancer (irrespective of diagnoses and staging) and extending well into survivorship. The underlying mechanisms of fatigue are not well understood and, as such, there could be many contributing factors (e.g., insomnia and mood disturbance). The present analysis is based on a pilot study evaluating whether sleep continuity and CRF is improved by CBT-I dose (4 & 8 [Low dose] vs 10 & 12 [High dose] sessions). The present analysis evaluates whether dose of CBT-I effects depression and anxiety in patients diagnosed with breast and prostate cancer. Methods This descriptive analysis (percent change from pre to post treatment) includes 12 adult subjects (83.3% female, Mage 58.4±7.5yrs.; [Low dose, n=6], [High dose, n=6]). CBT-I was provided by a master therapist via video conferencing (telehealth CBT-I). Subjects were asked to complete sleep diaries and weekly measures of fatigue (FACIT), insomnia severity (ISI), depression (PHQ-9), and anxiety (GAD-7). Results On the PHQ-9, subjects in the Low dose group exhibited a 57% improvement and subjects in the High dose group had a 52% improvement. On the GAD-7, this corresponded to a 26% improvement (High dose group) and 25% improvement. Conclusion As increasingly reported in the literature, CBT-I produced robust effects on depression as assessed by the PHQ-9. The effects on anxiety appear to be less robust. This may be the case because CBT-I’s effects on fatigue are likely to impact a variety of depressive symptoms, where this is less the case for anxiety. Analyses are ongoing, where the relative effects will be adjusted for insomnia-related items and rendered in terms of effect sizes. Support (if any) 5T32HL00795320;K24AG055602

0406 Impact of comorbid insomnia and nocturia on subjects' lives as assessed through a concept elicitation study

Abstract Introduction The lived experiences of individuals with insomnia and comorbid nocturia are not properly understood. This study explored the lived experiences of individuals with insomnia and comorbid nocturia to identify relevant concepts that could be reflected in patient-reported outcome (PRO) endpoints in clinical studies. Methods This was a cross-sectional, qualitative observational study. Data were collected from a sample of 10 adult subjects from the US suffering from insomnia disorder (DSM-5) and comorbid nocturia (≥2 nocturnal voids). Interviews were conducted using semi-structured guides, lasted 60–90 minutes, and assessed patient-relevant concepts of interest for their insomnia and nocturia. Institutional review board approval and web-based informed consent were obtained prior to the interviews. Results Overall, 10 participants were included, and the mean age was 61 years (SD=6). Most participants were female (8/10), White (9/10), and lived with a partner/spouse, family, or friends (8/10). Almost all participants experienced insomnia symptoms at least 5 nights per week (9/10), most often impacting their emotional (10/10), social (10/10), physical (9/10), cognitive (9/10), and work and productivity (6/10) functioning. Almost all participants reported that decreasing the impact of insomnia would be meaningful (8/10), most often mentioning improvements in physical impacts such as having more energy or feeling less exhausted (7/10). All participants experienced nocturia at least 6 nights per week (10/10), often impacting their emotional (7/10), social (6/10), physical (6/10), cognitive (4/10), and work and productivity (4/10) functioning. Participants reported that going to the bathroom less often (i.e., two times per night, once per night, or not at all; each 2/10) and being able to sleep through the night (2/10) would be meaningful improvements. Conclusion Individuals with insomnia and nocturia experience disrupted sleep patterns that impact their emotional, social, physical, cognitive, and work functioning. Feeling less tired, being able to sleep through the night, and getting up less often to use the bathroom would be meaningful to patients living with both conditions. Support (if any) Funded by Idorsia Pharmaceuticals Ltd.

0659 Nightmares in the acute aftermath of trauma predict later suicidal ideation in trauma survivors

Abstract Introduction Nightmares are a common occurrence after experiencing a traumatic event and are a symptom of post-traumatic stress disorder (PTSD). Additionally, nightmares are associated with higher levels of suicidal ideation, attempt, and death from suicide. Nightmares may be an early sign of suicide risk in populations that have experienced trauma, however, there are no studies that have investigated this potential link. This study aims to determine whether more severe nightmares in the aftermath of trauma will prospectively predict later suicidal ideation, independent of comorbid insomnia. Methods We recruited adults that were admitted to the intensive care unit at Henry Ford Hospital in Detroit after experiencing a DSM-5 Criterion A traumatic event (N = 76, Mage = 38.39, 65.8% male). Participants completed study surveys at three time points: T1 (an average of 6 days after trauma), T2 (two weeks after T1), and T3 (1 month after T1). Nightmare and insomnia severity were measured at T2 with the Nightmare Disorder Index (NDI) and Insomnia Severity Index (ISI), respectively. Suicidal ideation was measured at T3 using item nine on the Patient Health Questionnaire (PHQ-9). Results More severe nightmares in the acute aftermath of trauma (T2) predicted more severe SI two weeks later at T3 (β = 0.49, SE = .17, p = .004, R2 = .22). This association remained even after adjusting for T1 SI, T2 ISI, age, and sex (β = 0.36, SE = .18, p = .044, R2 = .31). Conclusion More severe nightmares in the acute aftermath of trauma predicted more severe SI one month after trauma, independent of comorbid insomnia symptoms and baseline suicidal ideation. These findings suggest that the onset of nightmares immediately after trauma may confer a unique risk for SI. In clinical practice, it may be useful to detect nightmares in the aftermath of trauma using brief measures such as the NDI. Trauma survivors that develop frequent and severe nightmares within the acute recovery phase could then be given targeted nightmare treatment to reduce the risk of later SI. Support (if any)

0514 Association of muscle distribution and insomnia severity in COMISA

Abstract Introduction Insomnia and obstructive sleep apnea(OSA) may co-exit, and it is now named comorbid insomnia and OSA(COMISA). Such combined condition is associated with increased morbidity, and impairment, which requires treatment for both insomnia and OSA. Bioelectrical impedance analysis(BIA) is a widely used convenient method of body composition. In OSA patients, muscle and fat distribution are different among different sex, and severity of OSA. We hypothesized that the muscle distributions in COMISA were different from OSA, which can help early identification COMISA to optimize treatment. Methods All the patients aged 18 or older with symptoms of sleep disturbances who visited single tertiary sleep clinic in Korea were enrolled from December 2017 to September 2022. All patients underwent structured sleep evaluation, insomnia severity index (ISI), overnight polysomnography and BIA. All patients with apnea-hypopnea index (AHI) 15 or greater were enrolled. The COMISA were classified by insomnia symptoms based on the ISI score greater than 15. Results Total of 3328 subjects were finally enrolled(79.7% males and 20.3% females), and among them 29.5%(n=981) was COMISA. Compare to OSA without insomnia symptoms COMISA were older(COMISA,56.6 ± 12.9, OSA,54.3 ± 13.3; p< 0.001), and were more likely to be female(COMISA,27.5%, OSA,17.3%; p< 0.001). Although AHI had no significance, apnea was lower, and hypopnea was higher in COMISA than OSA. The muscle distribution in COMISA was different compared to OSA in non-obese groups(BMI< 25). In both male and female, total muscle mass(MM), skeletal muscle mass(SMM), Rt and Lt arm(RAMM, LAMM), Rt and Lt leg(RLMM, LLMM), and trunk(TMM) muscle mass, and fat free mass(FFM) were significantly different between non-obese COMISA and OSA. The correlation analysis in non-obese COMISA group revealed that ISI is negative correlated with muscle masses in both sex (M:F); MM(M,F:rho:-0.09*,-0.16*), SMM(rho:-0.01*,-0.17*), RAMM(rho:-0.07*,-0.15*) LAMM(rho:-0.07*,-0.16*), RLMM(rho:-0.09*,-0,15*), LLMM(rho:-0.09*,-0.16*), TMM(rho:-0.08*,-0.17*), FFM (rho: -0.1*,-0.16*)[*p< 0.05]. Conclusion This study revealed that the muscle distribution is different in non-obese, male and female, moderate to severe COMISA population. And insomnia symptom severity has negative relation with trunk and limb muscle masses. Our study suggests possible insomnia symptoms among OSA patients have different pathomechanisms in relation to body muscle distribution. Support (if any)

0534 How objective sleep quality with Odds Ratio Product differs by diagnosis of COMISA, OSA, and insomnia

Abstract Introduction Recent research has highlighted differences in sleep quality for comorbid insomnia and obstructive sleep apnea (COMISA). We investigated how COMISA affects objective sleep quality measured with odds ratio product (ORP) compared to individuals without insomnia or moderate to severe OSA. Methods 410 participants (age 46.4±12.3; 174 females) recorded their sleep with in-home PSG using the Cerebra Sleep System and completed questionnaires. Sleep quality was measured using ORP derived from micro-analyzing frontal EEG channels. On the questionnaires, participants reported whether they experienced insomnia symptoms at least three times a week. Participants were classified as having no diagnosis if their RDI on the home PSG was < 15 and no insomnia symptoms. They were classified as insomnia only if they reported at least one insomnia symptom with an RDI < 15. They were classified as OSA only if they had an RDI ≥15 and reported no insomnia symptoms. Finally, they were classified as COMISA if they had an RDI ≥15 and reported at least one insomnia symptom. All analyses controlled for age and were corrected for multiple comparisons. Results 113(27.6%) patients were classified as having no diagnosis, 109(26.6%) as insomnia only, 83(20.2%) as OSA only, and 105(25.6%) as COMISA. There was a significant effect of diagnosis on ORPNREM (F3,405= 6.042, p<.001) and ORPTRT (F3,405= 3.799, p= 0.010). Participants with no diagnosis had lower ORPNREM than patients with OSA only (p= 0.039) and patients with COMISA (p<.001) and had lower ORPTRT than COMISA (p= 0.009). OSA severity based on the AHI was the only significant predictor of ORPNREM (p <.001, β= 0.321). Both AHI (p <.001, β=0.176) and number of insomnia symptoms (p=0.002, β=0.141) were significant predictors of ORPTRT. Conclusion Participants with no diagnosis had the lowest ORP indicative of better sleep quality than participants with evidence of sleep disorders. Having COMISA may have greater impacts on sleep quality than insomnia symptoms alone. OSA severity was the only predictor of poor sleep quality when looking at ORPNREM. Yet both OSA severity and insomnia symptoms were associated with higher ORPTRT indicating that individuals with COMISA may show alterations of sleep quality in different states throughout the night. Support (if any)

Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA)

Insomnia and obstructive sleep apnea (OSA) are common sleep disorders and frequently coexist (COMISA). Arousals from sleep may be a common link explaining the frequent comorbidity of both disorders. Respiratory arousal threshold (AT) is a physiologic measurement of the level of respiratory effort to trigger an arousal from sleep. The impact of COMISA on AT is not known. We hypothesized that a low AT is more common among COMISA than among patients with OSA without insomnia. Participants referred for OSA diagnosis underwent a type 3 sleep study and answered the insomnia severity index (ISI) questionnaire and the Epworth sleepiness scale. Participants with an ISI score ≥ 15 were defined as having insomnia. Sleep apnea was defined as an apnea hypopnea index (AHI) ≥ 15 events/h. Low AT was determined using a previously validated score based on 3 polysomnography variables (AHI, nadir SpO2 and the frequency of hypopneas). OSA-only (n = 51) and COMISA (n = 52) participants had similar age (61[52–68] vs 60[53–65] years), body-mass index (31.3[27.7–36.2] vs 32.2[29.5–38.3] kg/m2) and OSA severity (40.2[27.5–60] vs 37.55[27.9–65.2] events/h): all p = NS. OSA-only group had significantly more males than the COMISA group (58% vs 33%, p = 0.013. The proportion of participants with a low AT among OSA-only and COMISA groups was similar (29 vs 33%, p = NS). The similar proportion of low AT among COMISA and patients with OSA suggests that the respiratory arousal threshold may not be related to the increased arousability of insomnia.

0734 Gender Differences in US Military Personnel with Insomnia, Obstructive Sleep Apnea & Comorbid Insomnia and Obstructive Sleep Apnea

Abstract Introduction Women constitute approximately 17% of the military. Yet, relatively little is known regarding sleep disorders and comorbid diagnoses effecting this gender. The aim of this study was to determine if there were gender-related differences in symptoms of sleep disorders and sleep-related impairment, comorbid sleep, behavioral medicine, and traumatic brain injury (TBI) diagnoses and polysomnographic (PSG) variables in military personnel with insomnia, OSA, and comorbid insomnia and OSA (COMISA). Methods Participants were 372 military personnel (46.2% females, 53.8% males) with an average age of 37.7±7.46 years and median BMI of 28.4 (5.50) kg/m2. Based on clinical evaluation and video-PSG, participants were diagnosed with insomnia (n = 118, 71.2% female), OSA (n = 118, 28.8% female) and COMISA (n = 136, 39.7% female). Insomnia severity, excessive daytime sleepiness, sleep quality, nightmare disorder, sleep impairment, fatigue, posttraumatic stress disorder (PTSD), anxiety, depression symptoms, and traumatic brain injury (TBI) were evaluated with validated questionnaires. Descriptive statistics, parametric and non-parametric pairwise comparisons and effect-size analyses were used to assess differences between sexes in terms of variables of interest. Results Female service members had significantly greater symptoms of nightmare disorder, PTSD, anxiety, and depression than their male counterparts. There were no significant differences between males and females with insomnia or OSA in sleep-related symptoms, impairment, or PSG based apnea-hypopnea index (AHI). Male service members with COMISA had a significantly greater AHI; females with COMISA had significantly greater symptoms of nightmare disorder, PTSD and anxiety. Conclusion In the largest study to date to clinically evaluate sleep disorders in military personnel, COMISA was the most frequent diagnosis. Surprisingly, there were minimal differences in self-reported symptoms of sleep disorders and PSG characteristics. However, male servicemembers with COMISA have more severe sleep disordered breathing while female servicemembers with COMISA have greater mental health morbidity. Military service may result in distinct sleep disorder phenotype(s). Support (if any) This work was supported by the Defense Health Agency, Defense Medical Research and Development Program, Clinical Research Intramural Initiative for Military Women’s Health (DM170708; Mysliwiec) and the US Air Force (USAF) Air Force Materiel Command (AFMC), Wright Patterson Air Force Base, Ohio (FA8650-18-2-6953; Peterson).

Effect of Lemborexant on Sleep Onset and Maintenance in Patients with Comorbid Insomnia Disorder and Mild Obstructive Sleep Apnea (P4-13.001)

<h3>Objective:</h3> Evaluate the effects of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in multiple countries for the treatment of insomnia disorder, in patients with comorbid insomnia and obstructive sleep apnea (COMISA) of mild severity. <h3>Background:</h3> Insomnia and obstructive sleep apnea (OSA) are frequent comorbid sleep disorders. However, commonly prescribed hypnotic drugs may exacerbate pre-existing respiratory dysfunction. <h3>Design/Methods:</h3> Study E2006-G000-304 (Study 304; NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)-controlled and active-comparator (zolpidem tartrate extended release 6.25mg [ZOL]) study of LEM 5mg (LEM5) and LEM 10mg (LEM10). This post-hoc analysis included subjects age ≥55y with both insomnia disorder and mild OSA (apnea hypopnea index [AHI] ≥5 and &lt;15 events/h of sleep). Sleep onset (latency to persistent sleep [LPS]), sleep efficiency (SE = total sleep time/time in bed), wake after sleep onset (WASO), and WASO in the second half of the night (WASO2H) were assessed at Nights 1/2 (NT1/2) and Nights 29/30 (NT29/30) using polysomnography. <h3>Results:</h3> 40.8% of the population (n=410/1006) had mild OSA, with AHI (mean [SD]) at screening of 9.33 (2.9) events/h; median age 65y, and 83.9% were female. Changes from baseline in SE were larger (increased, indicating improvement) and significantly different for both LEM5 and LEM10 versus PBO and ZOL (P&lt;0.05) on NT1/2 and NT29/30. Compared with PBO, changes from baseline in LPS, WASO, and WASO2H were all larger (decreased, indicating improvement) and significantly different (P&lt;0.005) with LEM5 and LEM10 at both time points. Compared with ZOL, LEM10 produced significantly greater decreases from baseline for LPS, WASO, and WASO2H at NT1/2 and NT29/30 (P&lt;0.01, all assessments); and LEM5 on NT29/30 (P&lt;0.02, all assessments). LEM was well tolerated and consistent with its known safety profile. <h3>Conclusions:</h3> These results demonstrate the effectiveness of LEM versus PBO and ZOL in an older patient population with untreated COMISA of mild severity. <b>Disclosure:</b> Margaret Moline has received personal compensation for serving as an employee of EISAI, INC.. Margaret Moline has received intellectual property interests from a discovery or technology relating to health care. Margaret Moline has received personal compensation in the range of $0-$499 for serving as a review, loan repayment program with NIH. Dr. Cheng has received personal compensation for serving as an employee of Eisai Inc. Dinesh Kumar has received personal compensation for serving as an employee of Eisai. Dr. Ramos has received personal compensation for serving as an employee of Eisai. Dr. Lowe has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai . Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Paladin . Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sunovion . Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai . Dr. Lowe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion . The institution of Dr. Lowe has received research support from Axsome Therapeutics . The institution of Dr. Lowe has received research support from Boehringer Ingelheim .

Sex Differences at Presentation in Isolated Rapid Eye Movement Sleep Behavior Disorder (P6-13.003)

<h3>Objective:</h3> To compare clinical and demographic characteristics of iRBD at diagnosis in men and women. <h3>Background:</h3> Isolated REM sleep behavior disorder (iRBD) is male-predominant in older adults, yet has approximately equal frequency between women and men in younger adults. Data concerning clinical and demographic characteristics in women with iRBD remain limited. <h3>Design/Methods:</h3> We identified 130 women with PSG confirmed iRBD and matched them with 132 PSG-confirmed iRBD men who underwent PSG within 1 month of their female counterparts. Chart review was performed to extract relevant clinical and demographic information. Group comparisons were made with t-tests and chi square analyses. <h3>Results:</h3> Age at RBD symptom onset (50.4 ± 20.0 vs. 55.4 ±16.9 years, p=0.03) and diagnosis (56.4 ±16.7 vs. 62.5 ± 13.3 years, p&lt;0.01) was younger in women than in men. RBD-related injury frequency was similar between groups. Antidepressant use prior to RBD diagnosis (80.8% vs 53.0%, p&lt;0.01), psychiatric comorbidities (79.8% vs. 50.8%, p&lt;0.01) and chronic pain syndromes (39.2% vs. 17.4%, p&lt;0.01) were more frequent in women than men. Women also had more frequent comorbid insomnia (31.5% vs. 18.2%, p= 0.01), hypersomnia (50.8% vs 37.9%, p=0.04) and trended toward more frequent overlap parasomnia disorder (13.8% vs 9.8%, p=0.06) while obstructive sleep apnea (43.1% vs. 70.5%, p &lt; 0.01.) and vascular disease (62.3% vs 83.3%, p&lt;0.01) were more common in men. There were no differences in systemic autoimmune disease between sexes. <h3>Conclusions:</h3> Women with iRBD are younger at symptom onset and diagnosis, more likely to have psychiatric comorbidities and antidepressant use, and differ in profiles of comorbid sleep disturbances and medical comorbidities than men with iRBD. Awareness of key differences between the sexes in iRBD provides insight into possible etiologic factors and will enable clinicians to accurately diagnose iRBD and provide individualized recommendations. <b>Disclosure:</b> Dr. Alexandres has nothing to disclose. Dr. McCarter has nothing to disclose. Dr. Tabatabai has nothing to disclose. Mr. Feemster has nothing to disclose. Mr. Gossard has nothing to disclose. Paul Timm has nothing to disclose. Dr. Sandness has nothing to disclose. The institution of Dr. Carvalho has received research support from NIH. Mr. Jagielski has nothing to disclose. Emma Strainis has nothing to disclose. Laurene Leclair-Visonneau has nothing to disclose. Dr. Junna has nothing to disclose. Dr. Tippmann-Peikert has nothing to disclose. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. Dr. Lipford has nothing to disclose. Dr. Moore has nothing to disclose. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. Silber has received publishing royalties from a publication relating to health care. Dr. Silber has received personal compensation in the range of $500-$4,999 for serving as a Topic writer with UpToDate.

Transdiagnostic association between subjective insomnia and depressive symptoms in major psychiatric disorders.

In psychiatric disorders, comorbid depressive symptoms are associated with clinically important issues such as reduced quality of life, a poor prognosis, and increased suicide risk. Previous studies have found a close relationship between insomnia and depressive symptoms in major depressive disorder (MDD), and that actively improving insomnia heightens the improvement of depressive symptoms. This study aimed to investigate whether the association between insomnia and depressive symptoms is also found in other psychiatric disorders besides MDD. The subjects were 144 patients with MDD (n = 71), schizophrenia (n = 25), bipolar disorder (n = 22), or anxiety disorders (n = 26). Sleep status was assessed subjectively and objectively using the Athens Insomnia Scale (AIS) and sleep electroencephalography (EEG), respectively. Sleep EEG was performed using a portable EEG device. Depressive symptoms were assessed using the Beck Depression Inventory. Subjective insomnia, as defined by the AIS, was associated with depressive symptoms in all disorders. Moreover, in schizophrenia, a relation between depressive symptoms and insomnia was also found by objective sleep assessment methods using sleep EEG. Our findings suggest that the association between subjective insomnia and depressive symptoms is a transdiagnostic feature in major psychiatric disorders. Further studies are needed to clarify whether therapeutic interventions for comorbid insomnia can improve depressive symptoms in major psychiatric disorders, similar to MDD.

Sleep efficiency predicts improvements in fear extinction and PTSD symptoms during prolonged exposure for veterans with comorbid insomnia

Prolonged exposure (PE) is an evidenced-based psychotherapy for PTSD, but many Veterans fail to achieve a clinically meaningful response. Sleep issues are prevalent in Veterans and may interfere with PE by disrupting the learning and consolidation of fear extinction memories during PE exposures. Here, we examined whether changes in fear extinction across imaginal exposures and PTSD symptoms during PE were predicted by diary-assessed levels of nightly sleep efficiency (SE; i.e., percent of time in bed spent sleeping), which may indirectly index sleep fragmentation and sleep-facilitated memory processes. Participants were Veterans with PTSD and comorbid insomnia (N = 40) participating in a clinical trial of cognitive-behavioral therapy for insomnia plus PE. SE was measured via nightly sleep diaries, fear extinction was operationalized as a reduction in peak distress between weekly imaginal exposures, and PTSD symptoms were assessed bi-weekly. Cross-lagged panel models revealed that higher sleep efficiency during the week predicted lower peak distress at the subsequent imaginal exposure and lower PTSD symptoms at the subsequent assessment, whereas PTSD symptoms and peak distress did not predict subsequent sleep efficiency. Efficient sleep may facilitate fear extinction and PTSD reduction during PE. Targeting sleep efficiency could improve PE effectiveness for Veterans with comorbid insomnia.

Comorbid Insomnia and Sleep Apnea (COMISA) – a real problem for psychiatrists, pulmonologists, and primary care physicians

Introduction: Insomnia and obstructive sleep apnea are among the most common sleep-wake disorders. A relatively new category of disorders, studied more thoroughly for only a few years, is the occurrence of symptoms of both obstructive sleep apnea and insomnia in one patient and treating it as a different disease entity. This phenomenon is increasingly referred to as COMISA (Co-morbid insomnia and sleep apnea). The aim of this paper is to: 1) draw attention to this interesting issue, 2) show treatment differences of COMISA from isolated insomnia or obstructive sleep apnea and to help choose better therapy by general practitioners, pulmonologists, and psychiatrists for these patients. Materials and methods: The literature review was based on a search of articles in Medline, PubMed, and Google Scholar from 2012 to 2023 using the keywords: obstructive sleep apnea; insomnia; cognitive behavioral therapy for insomnia; continuous positive airway pressure; COMISA. The analysis included original studies, meta-analyses, and review articles. Discussion: The prevalence of both diseases in patients is importantly higher than in the general population. Many patients with COMISA or OSA alone remain undiagnosed. The most common examination of OSA requires a hospital stay to perform polysomnography or polygraphy (2). A lot of people are not willing to go through with the diagnostic process. Conclusions: It is important that during the standard medical history, doctors take into account the possibility of co-occurrence of these diseases, due to the high risk of not diagnosing them on time. Keywords: Obstructive sleep apnea, Insomnia, Cognitive behavioral therapy for insomnia, Continuous positive airway pressure, COMISA

New insights into chronic pain management based on biopsychosocial model

The biopsychosocial model of pain dominates the scientific community’s understanding of chronic pain. Chronic pain is considered a different form of depression. In this study, pain relief was explored in chronic pain patients with different neurological disease, accompanied by comorbid symptoms, depression, and insomnia. Twenty-three chronic pain patients aged 26–79 years with comorbid symptoms were included in a prospective 12-week treatment using 10 mg vortioxetine. Different types of chronic pain were represented in this study: low back pain (13 patients), headache (four patients); neuropathic mechanism-induced pain (six patients) – spinal stenosis (two patients), radiculopathy (two patients), and trigeminal neuralgia (two patients). Efficacy of vortioxetine treatment was monitored after 1 week, 3 weeks, and 12 weeks. Visual analog scale (VAS) was used for pain intensity value. Dynamic of pain relief was assessed in accordance with comorbid depression and insomnia. Most patients with chronic pain actively reported depression (65%) and insomnia (74%). Depression was statistically rare in patients with neuropathic pain (33%) compared to patients with nociceptive pain (82%; P &lt; 0.05). Incidence of insomnia was lower, although not statistically, in patients with neuropathic mechanism-induced pain (50%) compared to patients with nociceptive pain (82%, P = 0.129). Patients younger than 65 years reported pain reduction, according to VAS, after 1 week and 3 weeks vortioxetine therapy. The mean pain relief was 1.1 cm in young patients versus 0.16 cm in patients aged &gt;65 years (P &lt; 0.01) after 1-week treatment, and it was 2.35 cm in young patients versus 1.7 cm in patients aged &gt;65 years (P &lt; 0.05) after 3-week treatment. Vortioxetine therapy was effective in different types of chronic pain, accompanied by comorbid depression and insomnia. At early stage of treatment, pain relief was lower in old patients aged &gt;65 years. Regardless of age, all patients had significant pain relief after the 12-week treatment.

Is insomnia severity a moderator of the associations between obstructive sleep apnea severity with mood and diabetes-related distress?

This study examined insomnia severity as a moderator of the associations between obstructive sleep apnea (OSA) severity with impaired mood and diabetes-related distress in adults with OSA and type 2 diabetes (T2D). This secondary analysis used pooled baseline data from two randomized controlled trials that evaluated the efficacy of treatment of OSA or insomnia in adults with T2D. Participants for this analysis had OSA (ApneaHypopnea Index [AHI] ≥ five events/hour obtained from an in-home sleep apnea testing device) and completed questionnaires on insomnia, mood, and diabetes-related distress. Hierarchical multiple linear regression and multivariate linear regression analyses were used controlling for demographic characteristics and restless leg syndrome. Of 240 participants, mean age was 57.8 ± 10.17, 50% werefemale, and 35% werenon-White. Participants had poorly controlled diabetes (Mean HbA1C = 7.93 ± 1.62), and moderate OSA (Mean AHI = 19.3 ± 16.2). Insomnia severity significantly moderated the association between OSA severity and mood (b = -0.048, p = .017). Although insomnia severity did not moderate the relationship between OSA severity and diabetes-related distress (b = -0.009, p = .458), insomnia severity was independently associated with greater diabetes-related distress (b = 1.133, p < .001). In adults with T2D and OSA, as insomnia severity increased, increasing OSA severity was associated with lower level of mood disturbances. Insomnia independently increased the level of diabetes-related distress. These findings suggest that comorbid insomnia may be more impactful than OSA on increasing mood disturbances and diabetes-related distress in adults with T2D.

Network analysis of comorbid insomnia and depressive symptoms among psychiatric practitioners during the COVID-19 pandemic.

Insomnia and depression are common mental health problems reported by mental health professionals during the COVID-19 pandemic. Network analysis is a fine-grained approach used to examine associations between psychiatric syndromes at a symptom level. This study was designed to elucidate central symptoms and bridge symptoms of a depression-insomnia network among psychiatric practitioners in China. The identification of particularly important symptoms via network analysis provides an empirical foundation for targeting specific symptoms when developing treatments for comorbid insomnia and depression within this population. A total of 10,516 psychiatric practitioners were included in this study. The Insomnia Severity Index (ISI) and 9-item Patient Health Questionnaire (PHQ-9) were used to estimate prevalence rates of insomnia and depressive symptoms, respectively. Analyses also generated a network model of insomnia and depression symptoms in the sample. Prevalence rates of insomnia (ISI total score ≥8), depression (PHQ-9 total score ≥5) and comorbid insomnia and depression were 22.2% (95% confidence interval: 21.4-22.9%), 28.5% (95% confidence interval: 27.6-29.4%), and 16.0% (95% confidence interval: 15.3-16.7%), respectively. Network analysis revealed that "Distress caused by sleep difficulties" (ISI7) and "Sleep maintenance" (ISI2) had the highest strength centrality, followed by "Motor dysfunction" (PHQ8) and "Sad mood" (PHQ2). Furthermore, the nodes "Sleep dissatisfaction" (ISI4), "Fatigue" (PHQ4), and "Motor dysfunction" (PHQ8) had the highest bridge strengths in linking depression and insomnia communities. Both central and bridge symptoms (ie, Distress caused by sleep difficulties, Sleep maintenance, Motor dysfunction, Sad mood, Sleep dissatisfaction, and Fatigue) should be prioritized when testing preventive measures and specific treatments to address comorbid insomnia and depression among psychiatric practitioners during the COVID-19 pandemic. Zhao N, Zhao Y-J, An F, etal. Network analysis of comorbid insomnia and depressive symptoms among psychiatric practitioners during the COVID-19 pandemic. J Clin Sleep Med. 2023;19(7):1271-1279.

Economic burden of comorbid insomnia in 5 common medical disease subgroups.

Approximately 85% of insomnia co-occurs with other disorders. Whereas insomnia was once considered "secondary" to these disorders, it is now widely recognized as an independent condition warranting treatment. While it is clear that insomnia can affect the course of other medical conditions, there is scant literature on the economic impact of comorbid insomnia among patients with common medical conditions. The aim of this study was to determine the economic burden of comorbid insomnia in 5 medical diseases commonly associated with insomnia: type 2 diabetes mellitus (T2DM), cancer undergoing treatment, menopause undergoing hormone replacement therapy, osteoporosis, and Alzheimer's disease and related dementias (ADRDs). This retrospective cohort study used claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases from January 1, 2014, through December 31, 2019. Insomnia and comorbid disease groups were defined using physician-assigned International Classification of Diseases diagnostic codes. Insomnia medication treatment was defined based on ≥1 prescription fills for the most commonly prescribed insomnia medications (zolpidem, low-dose trazodone, and benzodiazepines [as a class]). For each comorbid disease subgroup, 4 cohorts were created: (1) patients with either treated or untreated insomnia, (2) non-sleep-disordered controls, (3) patients with untreated insomnia, and (4) patients with treated insomnia. Sample sizes for individuals with comorbid insomnia ranged from 23,168 (T2DM) to 3,015 (ADRDs). Within each disease subgroup and relative to non-sleep-disordered controls, patients with comorbid insomnia demonstrated greater adjusted health care resource utilization and costs across most points of service. Likewise, relative to individuals with untreated insomnia, those with treated insomnia generally demonstrated greater adjusted health care resource utilization and costs. In this national analysis, both untreated comorbid insomnia and comorbid insomnia treated with commonly prescribed insomnia medications were associated with increased health care resource utilization and costs across most points of service. Wickwire EM, Juday TR, Kelkar M, Heo J, Margiotta C, Frech FH. Economic burden of comorbid insomnia in 5 common medical disease subgroups. J Clin Sleep Med. 2023;19(7):1293-1302.

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia

AimTo investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant helps reduce the dose of benzodiazepines (BZs). MethodsThis retrospective observational study was conducted on outpatients and inpatients treated by physicians of Juntendo University Hospital Mental Clinic between April 2020 and December 2021. ResultsData of 649 patients who were treated with lemborexant were eventually enrolled. About 64.5% of patients were classified as the responder group. Response rates of ≥60% were recorded for most psychiatric disorders. Upon administration of lemborexant, diazepam-equivalent dose of BZs had been significantly reduced in participants (3.7 ± 8.2 vs. 2.9 ± 7.9, p < 0.001). The results of logistic regression analysis showed that outpatient (odds ratios: 2.310; 95% confidence interval [CI]: 1.32–4.05), shorter duration of BZ use (<1 year) (odds ratios: 1.512; 95% CI: 1.02–2.25), no adverse events (odds ratios: 10.369; 95% CI: 6.13–17.54), larger reduction of diazepam-equivalent dose of BZs upon introducing lemborexant prescription (odds ratios: 1.150; 95% CI: 1.04–1.27), and suvorexant was the replacement drug (odds ratios: 2.983; 95% CI: 1.44–6.19), which were significant predictors of good response. ConclusionAlthough this is a retrospective and observational study with many limitations, our study results suggest that lemborexant is effective and safe.

The effect of cognitive behavioural therapy for insomnia in people with comorbid insomnia and sleep apnoea: A systematic review and meta-analysis.

Comorbid insomnia and sleep apnoea (COMISA) is a highly prevalent and debilitating sleep disorder. Cognitive behavioural therapy for insomnia (CBTi) may be an appropriate treatment for COMISA; however, no previous study has systematically reviewed and meta-analysed literature reporting on the effect of CBTi in people with COMISA. A systematic literature search was conducted across PsychINFO and PubMed (n=295). In all, 27 full-text records were independently reviewed by at least two authors. Forward- and backward-chain referencing, and hand-searches were used to identify additional studies. Authors of potentially eligible studies were contacted to provide COMISA subgroup data. In total, 21 studies, including 14 independent samples of 1040 participants with COMISA were included. Downs and Black quality assessments were performed. A meta-analysis including nine primary studies measuring the Insomnia Severity Index indicated that CBTi is associated with a large improvement in insomnia severity (Hedges' g=-0.89, 95% confidence interval [CI] -1.35, -0.43). Subgroup meta-analyses indicated that CBTi is effective in samples with untreated obstructive sleep apnoea (OSA) (five studies, Hedges' g=-1.19, 95% CI -1.77, -0.61) and treated OSA (four studies, Hedges' g=-0.55, 95% CI -0.75, -0.35). Publication bias was evaluated by examining the Funnel plot (Egger's regression p=0.78). Implementation programmes are required to embed COMISA management pathways in sleep clinics worldwide that currently specialise in the management of OSA alone. Future research should investigate and refine CBTi interventions in people with COMISA, including identifying the most effective CBTi components, adaptations, and developing personalised management approaches for this highly prevalent and debilitating condition.

Should testing for obstructive sleep apnea be offered routinely to older family medicine patients? A prospective cohort study

ABSTRACT In our previous studies, we offered older family medicine patients testing for obstructive sleep apnea (OSA) and discovered that 80% of patients who accepted, were later diagnosed with unsuspected OSA. In the present study, we followed such patients for 3 years of usual treatment. The goals were to (1) observe whether wider testing for OSA would increase case recognition and treatment uptake; (2) identify symptom and health characteristics associated with diagnosis and treatment efficacy. 101 women and 75 men (>45 years) recruited from family medicine clinics completed questionnaires, polysomnography and consented to chart review (Time 1). Participants with OSA were offered treatment and follow-up with a sleep medicine specialist. All were re-evaluated after 3 years (Time 2). At Time 1, 93% of participants received a diagnosis of OSA. Of these, 53 initiated treatment (46 PAP therapy); at Time 2, 24 PAP users met criteria for adherence. PAP-adherent participants had worse OSA and worse reported symptoms at Time 1 than non-adherent participants. At Time 2, PAP-adherent participants improved on insomnia and daytime symptoms compared to non-adherent participants who showed no change. Adherent and non-adherent participants showed no difference in health indices at Time 1 and no change at three-year follow-up. Benefits of treatment included improvements in co-morbid insomnia and daytime functioning; however, offering wider testing for OSA to older, family medicine patients yielded a high rate of diagnosis but low treatment adoption and adherence. Therefore, a cost-effective strategy would identify and support those likely to adopt and adhere to treatment.

What Should Be the Focus of Treatment When Insomnia Disorder Is Comorbid with Depression or Anxiety Disorder?

Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of the mental health condition will generalize to sleep symptoms. An expert panel of seven members conducted a clinical appraisal of the literature regarding the treatment of insomnia when comorbid anxiety or depression are also present. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the panel's predetermined clinical focus statement, "Whenever chronic insomnia is associated with another condition, such as anxiety or depression, that psychiatric condition should be the only focus of treatment as the insomnia is most likely a symptom of the condition". The results from an electronic national survey of US-based practicing physicians, psychiatrists, and sleep (N = 508) revealed that >40% of physicians agree "at least somewhat" that treatment of comorbid insomnia should focus solely on the psychiatric condition. Whereas 100% of the expert panel disagreed with the statement. Thus, an important gap exists between current clinical practices and evidence-based guidelines and more awareness is needed so that insomnia is treated distinctly from comorbid anxiety and depression.