Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

The aim of this study was to assess age- and sex-related differences in multiple sleep latency test (MSLT) results and in the performance of the Epworth Sleepiness Scale (ESS) at classifying objective hypersomnia (mean sleep latency (MSL) ≤ 8 min). We studied 480 consecutive adults (39.3 ± 15.3 years old [18-93], 67.7% female) who underwent hypersomnia evaluation. We fit linear regression models to investigate associations between age and sex and sleep latencies (mean and for every nap), after adjusting for total sleep time and sleep efficiency (on polysomnography), and REM-suppressing antidepressant effect. A logistic regression was performed to assess whether age and sex were associated with sleep-onset REM period (SOREMP) occurrence. ROC analysis assessed the diagnostic performance of ESS scores to identify a MSL ≤ 8 min in different age/sex groups. For every 10 years of age, there was 0.41 (95% CI 0.11-0.72, p = 0.008) min reduction in MSL. Objectively (MSL ≤ 8 min) sleepy patients had shortening of latencies in naps 4 and 5 with aging. Female sex was associated with a higher MSL only in patients with MSL > 8 min. A 2.4% reduction in the odds of SOREMP occurrence was observed for every year of age in objectively sleepy patients (p = 0.045). ESS scores had a better diagnostic performance in older (≥ 50 years old) men than younger (< 50 years old) women (p < 0.05). Older patients with objectively confirmed hypersomnia may be sleepier in later naps, possibly due to less restorative naps and/or circadian rhythm factors. Self-reported sleepiness is more predictive of objective sleepiness in older men than younger women.

Correction: Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

[This corrects the article DOI: 10.1007/s41105-024-00512-5.].

Correlates to Improvement in Sleep Duration in Acute Mania and Depression.

Objective: To examine sleep duration at admission and discharge and change in sleep duration during hospitalization in patients experiencing a manic episode and compare these parameters to patients hospitalized for major depressive disorder (MDD) during the same time frame. The correlation between sleep duration parameters in those with mania and MDD with length of hospital stay, after accounting for possible confounders, was also examined.Methods: This retrospective study examined patients admitted to an acute care psychiatric unit from 2018 to 2021 with an episode of mania or MDD. Sleep duration was determined based on nursing observer report.Results: The study included 41 patients with mania (32.9 ± 1.7 years) and 38 patients with MDD (32.7 ± 1.8 years). Mania patients had longer hospitalization and received higher antipsychotic and benzodiazepine doses, but fewer hypnotics (all P < .005). No differences were found in sleep duration at admission (P = .109) and discharge (P = .623) in the mania and MDD groups. Change in sleep duration was 1.14 ± 0.27 and 0.37 ± 0.28 hours (P = .05) in the groups, respectively. In those with mania, sleep duration at admission negatively correlated with length of stay (r = -0.033; P = .03). Sleep duration parameters were not correlated with length of stay in patients with MDD.Conclusion: There was a trend toward greater improvement in sleep duration in inpatients with mania versus MDD. Sleep duration at admission correlated with length of hospitalization in patients with mania. Future studies should examine whether attempts to increase sleep duration can improve patient outcomes.Prim Care Companion CNS Disord 2024;26(1):23m03620. Author affiliations are listed at the end of this article.

Prevalence and associations of multiple hypnotic prescriptions in a clinical sample.

STUDY OBJECTIVES: We examined the prevalence of multiple hypnotic prescriptions and its association with clinical and demographic characteristics from the electronic health record (EHR) in the Mayo Clinic Biobank. METHODS: Adult participants enrolled in the Mayo Clinic Biobank with an EHR number of ≥ 1 year were included (n = 52,940). Clinical and demographic characteristics were compared between participants who were and were not prescribed any hypnotic approved for insomnia by the US Food and Drug Administration and/or trazodone and in those prescribed a single vs multiple (≥ 2) hypnotics. A phenotype-based, phenome-wide association study (PheWAS) examining associations between hypnotic prescriptions and diagnoses across the EHR was performed adjusting for demographic and other confounders. RESULTS: A total of 17,662 (33%) participants were prescribed at least 1 hypnotic and 5,331 (10%) received ≥ 2 hypnotics. Participants who were prescribed a hypnotic were more likely to be older, female, White, with a longer EHR, and a greater number of diagnostic codes (all P < .001). Those with multiple hypnotic prescriptions were more likely to be younger, female, with a longer EHR, and a greater number of diagnostic codes (all P < .001) compared with those prescribed a single hypnotic. The PheWAS revealed that participants with multiple hypnotic prescriptions had higher rates of mood disorders, anxiety disorders, suicidal ideation, restless legs syndrome, and chronic pain (all P < 1 e-10). CONCLUSIONS: Receiving multiple hypnotic prescriptions is common and associated with a greater prevalence of psychiatric, chronic pain, and sleep-related movement disorders. Future studies should examine potential genetic associations with multiple hypnotic prescriptions to personalize treatments for chronic insomnia. CITATION: Kolla BP, Mansukhani MP, Chakravorty S, Frank JA, Coombes BJ. Prevalence and associations of multiple hypnotic prescriptions in a clinical sample. J Clin Sleep Med. 2024;20(5):793-800.

Clinical Utility and Impact of Phosphatidylethanol Testing in Liver Transplantation Evaluations.

BACKGROUND: Phosphatidylethanol (PEth) is a serum biomarker that can detect alcohol use within the last 28 days with excellent sensitivity and specificity. Urinary ethyl glucuronide (uEtG) is commonly used in transplant settings to screen for alcohol use; however, it has several limitations relevant to liver transplantation. Transplant centers are beginning to regularly utilize PEth as part of the screening process for high-risk liver transplantation candidates although the clinical utility of uniform pre-transplant PEth testing is unclear. METHODS: This was a retrospective chart review of all patients evaluated for liver transplantation from December 1, 2019, through May 31, 2022, at a large academic tertiary referral center utilizing uniform serum PEth and uEtG screening. Information regarding the patients' transplantation status, age, sex, race, Model for End-Stage Liver Disease score, and PEth levels was obtained. In those with a positive PEth, we examined if the result would have been detected with uEtG, identified a discrepancy from the documented patient report of last use, led to a change in the Psychosocial Assessment of Candidate for Transplantation score, or influenced the transplant selection committee's decision. RESULTS: Our sample included 865 individuals (mean age = 55.20, 61.27% male and 82.54% white) with calculated Model for End-Stage Liver Disease-Sodium scores ranging from 6.43 to 50.65 (mean: 18.09; median: 16.46). Forty-eight patients were found to have a positive PEth (PEth range 20-1833); 75% of the sample had alcohol-associated liver disease. In 23 of 48 (47.91%) cases, the positive PEth identified alcohol use missed by a concomitant uEtG screen. A positive PEth test identified a discrepancy from patients' self-report in 29 (60.42%) cases and influenced the selection committee's decision in 28 cases (58.33%). CONCLUSION: Uniform pretransplant PEth screening of liver transplant candidates at the time of initial evaluation identified alcohol use that would have been missed by uEtG testing, identified discrepancies from the patient's self-report, and influenced clinical decision-making in a significant number of cases. These findings support the use of uniform PEth screening in liver transplantation evaluations.

Are clinical trials for insomnia recruiting real-world patients?

Recent Phase III trials of hypnotic medications that have led to Food and Drug Administration approval have severely restrictive eligibility criteria. One hundred patients referred for insomnia who received a hypnotic medication at a large tertiary referral center were identified. Data were extracted to evaluate whether these patients would be eligible to be included in any of the recent Phase III trials. Of the 100 patients identified, only 3 were eligible. Most were excluded because of a prior or concurrent trial of cognitive behavioral therapy for insomnia. If this criterion were set aside, only 12% would have been eligible to participate. The remaining top reasons for exclusion were medical comorbidities, daytime napping, and sleep apnea. These findings question the generalizability of the regulatory studies and suggest that future trials should enroll patients with less-restrictive criteria to help determine the effectiveness of these medications in real-world settings. CITATION: Golebiowski R, Mansukhani MP, Kolla BP. Are clinical trials for insomnia recruiting real-world patients? J Clin Sleep Med. 2023;19(8):1553-1555.

Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (ß = -0.16, p = 0.0012) but not in women (ß = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies.

The Interaction Between Brain-Derived Neurotrophic Factor Levels and Alcohol Consumption, Sleep Disturbance and Sex-Hormones in Alcohol Use Disorders.

AIMS: Brain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors. METHODS: Data from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model. RESULTS: No significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = -0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found. CONCLUSION: Our study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker.

Prophylactic Use of Ramelteon for Delirium in Hospitalized Patients: A Systematic Review and Meta-Analyses.

BACKGROUND: Small prospective studies, case reports, as well as some randomized placebo-controlled trials and previous meta-analyses have shown that ramelteon, a melatonin agonist, may reduce the risk of developing delirium. OBJECTIVE: The goal of this systemic review and meta-analyses was to assess the current evidence supporting the use of ramelteon in delirium prevention by including data from larger (>100 subjects) and more recent trials since the most recent meta-analyses were published in 2019. There were no exclusions for trial size, age, ramelteon dose, length of treatment, or hospital setting. METHODS: Medline, Embase, PsycINFO, EBM Reviews, Scopus, and Web of Science databases were queried using the search terms delirium (with subterms including prevention and control), ramelteon, Rozerem, or melatonin receptor agonists, for English-language publications until March 16, 2021. Randomized placebo-controlled trials of hospitalized subjects receiving ramelteon for delirium prevention were included. The primary outcome of interest was delirium incidence. Odds ratios of the risk of developing incident delirium and 95% confidence intervals were calculated using a random effects model. RESULTS: A total of 177 articles were identified by the literature search. Five studies (n = 443, 53.7% male) met criteria for inclusion in the final meta-analyses. The meta-analyses of the randomized placebo-controlled trials revealed that ramelteon did not result in a reduction in the risk of incident delirium (n = 443; odds ratio = 0.49; 95% confidence interval = 0.13-1.85). A moderate degree of heterogeneity was noted among the studies (I2 = 53%). CONCLUSIONS: Current evidence suggests that ramelteon is ineffective as a prophylactic drug in reducing the incidence of delirium in hospitalized patients.

Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder.

STUDY OBJECTIVES: To describe the development and feasibility of a cognitive behavioral therapy for insomnia (CBT-I) program delivered via personal digital devices and fully integrated with the electronic health record (EHR). METHODS: A multidisciplinary team of clinicians and members of our Center for Digital Health collaborated to develop a Chronic Insomnia Interactive Care Plan (ChI-ICP), an application that provides personalized and just in time education and promotes self-management using CBT-I concepts, and is activated from and fully integrated into the EHR. Following development, we evaluated patient engagement and workflows, assessed changes to provider workload, and examined outcomes on measures of insomnia during a pilot deployment of the application. RESULTS: A total of 222 patients were enrolled and 179 engaged with the plan during the 3-month pilot program. Enrolled patients generated an average of 3.9 ± 2.3 In Basket messages, most being automated notifications related to noncompletion of assigned tasks, while only a few were related to patients requesting additional training or help with insomnia. Sleep efficiency improved from baseline until the completion of the program from 74.5% ± 16.7% to 87.6% ± 10.8% (P = .001), and the Insomnia Severity Index improved from 14.9 ± 5.22 to 11.6 ± 4.80 (P = .006). CONCLUSIONS: In this pilot implementation of an integrated ChI-ICP, patient engagement was favorable, workflows and workload were not significantly burdensome for the care teams, and initial evaluation of efficacy was favorable. This provides evidence for an application that is a scalable method to assist patients with chronic insomnia and future work should assess its efficacy in controlled trials. CITATION: Morgenthaler TI, Kolla BP, Anderson SE, et al. Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder. J Clin Sleep Med. 2022;18(12):2785-2792.

Delayed onset sleep-related stridor due to radiation for thyroid cancer.

Radiation therapy is the mainstay of treatment for head and neck cancers with both acute and delayed complications. While obstructive sleep apnea is common in the few series of patients undergoing radiation therapy to the neck, the development of sleep-related stridor is exceedingly rare and has typically been reported in the acute treatment setting. We describe a 65-year-old female with 1 year of nocturnal groaning beginning 2 years after radiation therapy for thyroid carcinoma. Polysomnography revealed mild obstructive sleep apnea and sleep-related stridor responsive to nasal continuous positive airway pressure. Our case highlights the importance of screening patients with a history of head and neck radiation for sleep-related breathing complaints at each follow-up visit and consideration of both obstructive sleep apnea and stridor in these patients. Identification of sleep-disordered breathing in these patients may lead to timely treatment and improvement in quality of life. CITATION: McCarter SJ, Mansukhani MP, Herold DL, Kolla BP. Delayed onset sleep-related stridor due to radiation for thyroid cancer. J Clin Sleep Med. 2022;18(9):2327-2329.

The Effects of Cannabinoids on Sleep.

The use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withdrawal from cannabinoids can lead to sleep disturbance. Here, we describe a patient who developed significant insomnia leading to worsening anxiety, mood, and suicidal ideation in the setting of medical cannabis withdrawal, prompting presentation to the Emergency Department and inpatient admission. There is a limited evidence base for the use of cannabis products for sleep. We provide a comprehensive review evaluating the literature on the use of cannabis products on sleep, including an overview of cannabis and related psychoactive compounds, the current state of the law as it pertains to the prescribing and use of these substances, and potential side effects and drug interactions. We specifically discuss the impact of cannabis products on normal sleep and circadian sleep-wake rhythms, insomnia, excessive daytime sleepiness, sleep apnea, parasomnias, and restless legs syndrome. We also describe the effects of cannabis withdrawal on sleep and how this increases relapse to cannabis use. Most of the studies are observational but the few published randomized controlled trials are reviewed. Our comprehensive review of the effects of cannabis products on normal sleep and sleep disorders, relevant to primary care providers and other clinicians evaluating and treating patients who use these types of products, shows that cannabis products have minimal to no effects on sleep disorders and may have deleterious effects in some individuals. Further research examining the differential impact of the various types of cannabinoids that are currently available on each of these sleep disorders is required.

Effects of transcranial magnetic stimulation on sleep quality and mood in patients with major depressive disorder.

STUDY OBJECTIVES: It is unknown whether sleep quality improvements after repetitive transcranial magnetic stimulation (rTMS) are inherent to the intervention or related to improvements in depressive symptoms. This retrospective study examined sleep quality in patients with major depressive disorder before and after treatment with rTMS, adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, depression severity, and changes in depressive symptoms. METHODS: Adults with major depressive disorder underwent a 6-week course of 10 Hz rTMS over the left dorsolateral prefrontal cortex. Patients completed the Patient Health Questionnaire-9 depression rating scale and the Pittsburgh Sleep Quality Index before and after treatment. To limit confounding, analysis of depressive symptoms occurred without item 3 (the sleep item) of the Patient Health Questionnaire-9. RESULTS: Twenty-one patients completed the study, with a mean (± standard deviation) baseline Pittsburgh Sleep Quality Index score of 12.0 (± 3.8), compared to 10.5 (± 4.3) posttreatment (P = .01). The mean baseline Patient Health Questionnaire-9 score without item 3 was 17.3 (± 3.0), compared to 12.2 (± 4.9) posttreatment (P = .0001). Pittsburgh Sleep Quality Index and modified Patient Health Questionnaire-9 changes were uncorrelated in nonadjusted and adjusted linear regression models and in the Spearman rank-order correlation. CONCLUSIONS: Mood and sleep quality improved independently after rTMS treatment, even after adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, and depression severity. These findings suggest that rTMS exerts direct effects on both mood and sleep in patients with major depressive disorder. CITATION: Collins AR, Cheung J, Croarkin PA, Kolla BP, Kung S. Effects of transcranial magnetic stimulation on sleep quality and mood in patients with major depressive disorder. J Clin Sleep Med. 2022;18(5):1297-1305.

Prevalence of insomnia symptoms and associated risk factors in UK Biobank participants with hazardous alcohol use and major depression.

INTRODUCTION: We aimed to examine the prevalence of insomnia symptoms (IS), sleep duration, and associated risk factors in participants with hazardous/harmful alcohol use (HAU), major depressive disorders (MDD), and HAU+MDD. METHODS: Data from the UK Biobank (UKB) (n = 55,000) were utilized to categorize participants into those with MDD (n = 5612), HAU (n = 15,893), MDD+HAU (n = 3738), and controls (n = 29,511). We examined whether rates of IS and sleep duration differed among the groups and determined the clinical predictors of IS. Rates of IS and sleep duration were compared using regression analyses accounting for demographic (age, sex, ethnicity, Townsend deprivation index) and clinical (body mass index, neuroticism score, alcohol consumption) factors. RESULTS: The unadjusted prevalence of IS was 26.5%, 27%, 39.5%, and 43% in control, HAU, MDD, and MDD+HAU categories respectively. Rates of IS in controls versus HAU and MDD versus MDD+HAU did not differ in unadjusted models (p = 0.45 and 0.075, respectively). Prevalence of IS differed in the four groups (p < 0.0001 for all pairwise comparisons) after adjusting for demographic confounders. After further adjustment for clinical factors, effect sizes were reduced, but pairwise comparisons remained significant. After adjusting for demographic and clinical factors, sleep duration did not differ among the groups. After accounting for diagnostic category and demographic/clinical factors, older age (OR=1.33 per 10 year increase; p < 0.0001), female sex (OR=1.39; p < 0.0001), obesity (OR=1.17 compared to normal; p < 0.0001), higher neuroticism score (OR=1.13; p < 0.0001), and alcohol consumption (OR=1.01 per serving increase; p < 0.0001) were associated with IS. CONCLUSION: Sleep-related morbidity is the greatest in the MDD+HAU group, followed by the MDD group. Demographic and clinical characteristics explain some, but not all of the differences in the prevalence of IS in MDD±HAU. Genetic and other factors capable of influencing IS in those with MDD, HAU, and MDD+HAU merit future investigation.

Challenges in the Treatment of Restless Legs Syndrome: A Case Report.

Treatment resistant restless legs syndrome (RLS) in the setting of psychiatric comorbidities can be difficult to manage. Our patient is a 69-year-old Caucasian gentleman with bipolar disorder type I, unspecified anxiety disorder, obstructive sleep apnea (OSA), and treatment-refractory RLS. At initial presentation, the patient's prescribed medication regimen included fluoxetine 40 mg daily, gabapentin 800 mg in the morning and 3200 mg at bedtime, pramipexole 0.375 mg daily, lamotrigine 200 mg daily, trazodone 200 mg at bedtime, and temazepam 15 to 30 mg as needed for insomnia and RLS. Over the course of nearly 4 years, treatment interventions for this patient's RLS included: cognitive behavioral therapy for insomnia, discontinuation of exacerbating medications, switching dopamine agonists, use of pregabalin and iron supplement. This report demonstrates a challenging case of RLS in the setting of psychiatric comorbidities, development of augmentation, and polypharmacy.

The influence of antidepressants and actigraphy-derived sleep characteristics on pediatric multiple sleep latency testing.

STUDY OBJECTIVES: Research evaluating the influence of rapid eye movement suppressing antidepressants (REMS-AD) on multiple sleep latency test (MSLT) results and the value of performing actigraphy prior to this test in children and adolescents is lacking. We examined the impact of REMS-AD and actigraphy parameters on mean sleep latency (MSL) and sleep-onset REM episodes (SOREMs) on MSLT in a pediatric clinical sample. METHODS: This was a retrospective chart review at a quarternary referral center. We identified 164 MSLTs conducted in patients aged less than 18 years between 2014 and 2017. Correlations between REMS-AD, self-reported sleep duration, actigraphy parameters, and each of the outcomes (MSL and SOREMs) were examined. Regression analyses accounting for clinical characteristics were performed. RESULTS: Mean age of the sample was 11.9 ± 4.19 years, 62% were female, 28 (17%) were on REMS-AD (48% of whom were able to discontinue these medications prior to MSLT), and mean pediatric daytime sleepiness score was 21.7 ± 6.1. MSL was 11.27 ± 5.77 min and mean number of SOREMs 0.55 ± 1.04. Patients on a REMS-AD at initial assessment had fewer SOREMs compared to those not taking these medications (0.17 ± 0.19 vs 0.62 ± 0.09; P = .04); no difference was noted in MSL (10.36 ± 1.10 vs 11.47 ± 0.50; P = .36). Increased time in bed on actigraphy correlated with a longer MSL and fewer SOREMs (r = .23; P = .04 and r = .316; P = .004, respectively). Following regression analyses, use of REMS-AD continued to remain associated with fewer SOREMs; greater time in bed on actigraphy, but not self-reported sleep duration, was associated with a longer MSL (all P < .05). CONCLUSIONS: Clinicians should account for the use of REMS-AD and utilize actigraphy to determine time in bed while interpreting the results of a pediatric MSLT. CITATION: Mansukhani MP, Dhankikar S, Kotagal S, Kolla BP. The influence of antidepressants and actigraphy-derived sleep characteristics on pediatric multiple sleep latency testing. J Clin Sleep Med. 2021;17(11):2179-2185.

Excessive Daytime Sleepiness: A Clinical Review.

Excessive daytime sleepiness (EDS) is a highly prevalent condition that is associated with significant morbidity. The causes of EDS are varied, and include inadequate sleep, sleep disordered breathing, circadian rhythm sleep-wake disorders, and central disorders of hypersomnolence (narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome). Additionally, EDS could represent a symptom of an underlying medical or psychiatric disorder. Assessment of EDS includes a thorough sleep, medical, and psychiatric history, targeted clinical examination, and appropriate use of actigraphy to measure sleep duration and sleep-wake patterns, polysomnography to assess for associated conditions such as sleep-related breathing disorders or other factors that might disrupt nighttime sleep, multiple sleep latency testing to ascertain objective sleepiness and diagnose central disorders of hypersomnolence, and measurement of cerebrospinal fluid hypocretin-1 concentration. Treatment of EDS secondary to central disorders of hypersomnolence is primarily pharmacologic with wakefulness-promoting agents such as modafinil, stimulants such as methylphenidate and amphetamines, and newer agents specifically designed to improve wakefulness; behavioral interventions can provide a useful adjunct to pharmacologic treatment. When excessive sleepiness is secondary to other conditions, the treatment should focus on targeting the primary disorder. This review discusses current epidemiology, provides guidance on clinical assessments and testing, and discusses the latest treatment options. For this review, we collated the latest evidence using the search terms excessive sleepiness, hypersomnia, hypersomnolence, treatment from PubMed and MEDLINE and the latest practice parameters from the American Academy of Sleep Medicine.

The Association of Sleep Apnea and Cardiorespiratory Fitness With Long-Term Major Cardiovascular Events.

OBJECTIVE: To determine the risk of long-term major adverse cardiovascular events (MACE) when sleep-disordered breathing (SDB) and decreased cardiorespiratory fitness (CRF) co-occur. METHODS: We included consecutive patients who underwent symptom-limited cardiopulmonary exercise tests between January 1, 2005, and January 1, 2010, followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-to-severe SDB (apnea/hypopnea index ≥15 per hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO2). Long-term MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke or transient ischemic attack (TIA), and death, assessed until May 21, 2018. Cox-proportional hazard models were adjusted for factors known to influence CRF and MACE. RESULTS: Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5 to 10.3 years). After adjusting for age, sex, beta blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking, and use of positive airway pressure (PAP), decreased CRF alone (hazard ratio [HR]=1.91, 95% confidence interval [CI], 1.15 to 3.18; P=.01), but not SDB alone (HR=1.26, 95% CI, 0.75 to 2.13, P=.39) was associated with increased risk of MACE. Those with SDB and decreased CRF had greater risk of MACE compared with patients with decreased CRF alone (HR=1.85; 95% CI, 1.21 to 2.84; P<.005) after accounting for these confounders. The risk of MACE was attenuated in those with reduced CRF alone after additionally adjusting for adequate adherence to PAP (HR=1.59; 95% CI, 0.77 to 3.31; P=.21). CONCLUSION: The incidence of MACE, especially mortality, was high in this sample. Moderate-to-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of possibly including CRF in the risk assessment of patients with SDB and, conversely, that of screening for SDB in patients with low peak VO2.

Pharmacological Management of Insomnia.

Insomnia is a highly prevalent condition associated with significant morbidity, reduction in quality of life, and increase in healthcare costs, and is a risk factor for multiple physical and mental disorders. The primary treatment modality is cognitive behavioral therapy for insomnia (CBT-I) but this is associated with difficulties with access and higher cost as well as poor response in some patients. Therefore, pharmacotherapy for insomnia is common and hypnotic agents are among the most frequently prescribed medications in the United States. Older medications for insomnia are limited by their side effect burden and narrow therapeutic window. Newer hypnotics, on the other hand, have been shown to have a better safety profile and longer term efficacy. While some studies have shown that long-term hypnotic use is associated with adverse outcomes, the current evidence is equivocal. The decision to treat chronic insomnia disorder with long-term hypnotics should be individualized and balance the potential risks of continuing hypnotic medication use with the risks of untreated persistent insomnia and associated functional limitations. This clinical review discusses the currently available medication options to treat insomnia, their mechanisms of action, dosing, and side effect profiles. This review also provides guidance on long-term management of hypnotics and the use of these medications in the elderly, those with medical comorbidities, and other special populations.