JCSM Articles

Obstructive Sleep Apnea and the Subsequent Risk of Depressive Disorder: A Population-Based Follow-up Study

Study Objectives:

Empirical findings on the prospective link between obstructive sleep apnea (OSA) and subsequent depression are mixed. This nationwide, population-based study thus aimed at assessing the risk of depressive disorder within the first year following a diagnosis with OSA. Gender effects were further examined.

Design:

Cohort study.

Setting:

Taiwan.

Patients:

This study used data from the Longitudinal Health Insurance Database 2000. A total of 2,818 patients diagnosed with OSA between 2002 and 2008 were evaluated, and 14,090 matched non-OSA enrollees used as a comparison cohort.

Measurements and Results:

Each patient was followed for one year to identify subsequent depressive disorder. We found that during the one-year follow-up, the incidence of depressive disorder per thousand person-years was about twice as high among patients with OSA (18.10, 95% CI = 13.62-23.61) as those without OSA (8.23, 95% CI = 6.83-9.84). The Cox proportional hazards model revealed that patients with OSA were independently associated with a 2.18 times (95% CI = 1.55-3.08) increased risk of subsequent depressive disorder within a year, compared to those without OSA. As epidemiological studies have consistently documented an increased risk for depression in women, we hypothesized and confirmed higher risks of depressive disorder among female patients with OSA (2.72, 95% CI = 1.68-4.40) than their male counterparts (1.81, 95% CI = 1.09-3.01).

Conclusion:

A prospective link between OSA and subsequent depressive disorder within one year was confirmed by the current study. The risk was particularly evident among women. Regular psychiatric screening among patients with OSA is suggested to prompt the timely detection of depression.

Commentary:

A commentary on this article appears in this issue on page 425.

Citation:

Chen YH; Keller JK; Kang JH; Hsieh HJ; Lin HC. Obstructive sleep apnea and the subsequent risk of depressive disorder: a population-based follow-up study. J Clin Sleep Med 2013;9(5):417-423.

The Link between OSA and Depression: Another Reason for Integrative Sleep Medicine Teams

Obstructive Sleep Apnea after Weight Loss: A Clinical Trial Comparing Gastric Bypass and Intensive Lifestyle Intervention

Introduction:

Few studies have compared the effect of surgical and conservative weight loss strategies on obstructive sleep apnea (OSA). We hypothesized that Roux-en-Y gastric bypass (RYGB) would be more effective than intensive lifestyle intervention (ILI) at reducing the prevalence and severity of OSA (apnea-hypopnea-index [AHI] ≥ 5 events/hour).

Methods:

A total of 133 morbidly obese subjects (93 females) were treated with either a 1-year ILI-program (n = 59) or RYGB (n = 74) and underwent repeated sleep recordings with a portable somnograph (Embletta).

Results:

Participants had a mean (SD) age of 44.7(10.8) years, BMI 45.1(5.7) kg/m², and AHI 17.1(21.4) events/hour. Eighty-four patients (63%) had OSA. The average weight loss was 8% in the ILI-group and 30% in the RYGB-group (p < 0.001). The mean (95%CI) AHI reduced in both treatment groups, although significantly more in the RYGB-group (AHI change -6.0 [ILI] vs -13.1 [RYGB]), between group difference 7.2 (1.3, 13.0), p = 0.017. Twenty-nine RYGB-patients (66%) had remission of OSA, compared to 16 ILI-patients (40%), p = 0.028. At follow-up, after adjusting for age, gender, and baseline AHI, the RYGB-patients had significantly lower adjusted odds for OSA than the ILI-patients—OR (95% CI) 0.33 (0.14, 0.81), p = 0.015. After further adjustment for BMI change, treatment group difference was no longer statistically significant—OR (95% CI) 1.31 (0.32, 5.35), p = 0.709.

Conclusion:

Our study demonstrates that RYGB was more effective than ILI at reducing the prevalence and severity of OSA. However, our analysis also suggests that weight loss, rather than the surgical procedure per se, explains the beneficial effects.

Citation:

Fredheim JM; Rollheim J; Sandbu R; Hofsø D; Omland T; Røislien J; Hjelmesaeth J. Obstructive sleep apnea after weight loss: a clinical trial comparing gastric bypass and intensive lifestyle intervention. J Clin Sleep Med 2013;9(5):427-432.

Evaluation of Drug-Induced Sleep Endoscopy as a Patient Selection Tool for Implanted Upper Airway Stimulation for Obstructive Sleep Apnea

Study Objectives:

To study the possible predictive value of drug-induced sleep endoscopy (DISE) in assessing therapeutic response to implanted upper airway stimulation (UAS) for obstructive sleep apnea (OSA).

Methods:

During DISE, artificial sleep is induced by midazolam and/or propofol, and the pharyngeal collapse patterns are visualized using a flexible fiberoptic nasopharyngoscope. The level (palate, oropharynx, tongue base, hypopharynx/epiglottis), the direction (anteroposterior, concentric, lateral), and the degree of collapse (none, partial, or complete) were scored in a standard fashion.

Results:

We report on the correlation between DISE results and therapy response in 21 OSA patients (apnea-hypopnea index [AHI] 38.5 ± 11.8/h; body mass index [BMI] 28 ± 2 kg/m², age 55 ± 11 y, 20 male/1 female) who underwent DISE before implantation of a UAS system. Statistical analysis revealed a significantly better outcome with UAS in patients (n = 16) without palatal complete concentric collapse (CCC), reducing AHI from 37.6 ± 11.4/h at baseline to 11.1 ± 12.0/h with UAS (p < 0.001). No statistical difference was noted in AHI or BMI at baseline between the patients with and without palatal CCC. In addition, no predictive value was found for the other DISE collapse patterns documented.

Conclusions:

The absence of palatal CCC during DISE may predict therapeutic success with implanted UAS therapy. DISE can be recommended as a patient selection tool for implanted UAS to treat OSA.

Citation:

Vanderveken OM; Maurer JT; Hohenhorst W; Ha-mans E; Lin HS; Vroegop AV; Anders C; de Vries N; Van de Heyning PH. Evaluation of drug-induced sleep endoscopy as a patient selection tool for implanted upper airway stimulation for obstructive sleep apnea. J Clin Sleep Med 2013;9(5):433-438.

Impact of Zaleplon on Continuous Positive Airway Pressure Therapy Compliance

Study Objective:

To determine whether pretreatment with zaleplon immediately before CPAP titration improves 1-month CPAP adherence in subjects newly diagnosed with OSA.

Methods:

Prospective, randomized, double-blinded, placebo-controlled trial of a single dose of zaleplon 10 mg or matching placebo at the start of CPAP titration during laboratory-based, split-night polysomnography (PSG). Baseline sleep symptoms were assessed with the Functional Outcomes of Sleep Questionnaire (FOSQ) and Epworth Sleepiness Scale (ESS). CPAP usage and change in symptom questionnaire responses were assessed at 1-month follow-up.

Results:

One hundred thirty-four newly diagnosed OSA patients undergoing their initial split-night PSG (49.8 ± 11.3 years old with an apnea-hypopnea index of 16.5 (7, 32) [median (interquartile range)] were randomized to zaleplon (n = 73) or placebo (n = 63). Complete follow-up data were available in 83 subjects (44 zaleplon group; 39 placebo group). CPAP was used for 6.5 (5, 7) h/day with zaleplon versus 6.5 (5, 8) h/ day with placebo (p = 0.64). Improvements in FOSQ and ESS scores did not differ between the two groups.

Conclusion:

A single dose of zaleplon at the start of a split-night CPAP titration does not result in superior CPAP adherence or improvement in symptoms at 1-month compared to placebo. Our data show that zaleplon is safe and is associated with shorter sleep latency during CPAP titration, but it does not translate into improved short-term CPAP adherence.

Citation:

Park JG; Olson EJ; Morgenthaler TI. Impact of zaleplon on continuous positive airway pressure therapy compliance. J Clin Sleep Med 2013;9(5):439-444.

Effects of Armodafinil on Simulated Driving and Self-Report Measures in Obstructive Sleep Apnea Patients prior to Treatment with Continuous Positive Airway Pressure

Study Objectives:

Obstructive sleep apnea (OSA) has been associated with an increased risk of motor vehicle crashes. This driving risk can be reduced (≥ 50%) by treatment with continuous positive airway pressure (CPAP). However residual excessive daytime sleepiness (EDS) can persist for some patients who regularly use CPAP. The current study was designed to assess the effect of armodafinil on simulated driving performance and subsequent CPAP treatment compliance in newly diagnosed OSA patients with EDS during a 2-week “waiting period” prior to initiation of CPAP.

Methods:

Sixty-nine newly diagnosed OSA patients, awaiting CPAP therapy, were randomized (1:1) to placebo or armodafinil (150 mg/day) treatment. Simulated driving tests and self-report measures were completed at baseline, after 2 weeks of drug treatment, and following 6 weeks of CPAP treatment. CPAP compliance was evaluated at the end of 6 weeks of CPAP.

Results:

Compared to placebo, armodafinil improved simulated driving safety performance in OSA patients awaiting CPAP therapy (p = 0.03). Improvement was seen in lane position deviation (p = 0.002) and number of lane excursions (p = 0.02). Improvement was also observed on measures of sleepiness using the Epworth Sleepiness Scale (ESS) and sleep related quality of life. Following 6 weeks of CPAP, there was also significant improvement observed on multiple measures of simulated driving performance. CPAP compliance did not differ between armodafinil-treated and placebo-treated patients (p = 0.80).

Conclusions:

Armodafinil was found to improve simulated driving performance in OSA patients with EDS prior to initiation of CPAP. Treatment with armodafinil showed no effect on subsequent CPAP compliance.

Citation:

Kay GG; Feldman N. Effects of armodafinil on simulated driving and self-report measures in obstructive sleep apnea patients prior to treatment with continuous positive airway pressure. J Clin Sleep Med 2013;9(5):445-454.

The Prevalence of Restless Legs Syndrome across the Full Spectrum of Kidney Disease

Study Objectives:

Although restless legs syndrome (RLS) is common and well recognized as an important and potentially treatable cause of sleep disruption in end-stage renal disease (ESRD), few studies have evaluated the prevalence of RLS and its impact on sleep in the non-dialysis-dependent chronic kidney disease (CKD) population. The objectives of the study were to determine the prevalence of RLS across the full spectrum of kidney disease and to assess the impact of RLS on sleep quality and daytime function.

Methods:

Five hundred patients were recruited from nephrology clinics and were stratified according to estimated glomerular filtration rate (eGFR): eGFR ≥ 60 mL/min/1.73m² (n = 127), CKD (eGFR < 60, not on dialysis, n = 242), and ESRD (on hemodialysis, n = 131). All subjects completed a sleep and medical history questionnaire, an RLS questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS).

Results:

The prevalence of RLS did not differ among the three groups (18.9% [eGFR ≥ 60], 26% (CKD), and 26% (ESRD) p = 0.27). However, many symptoms of sleep disruption were more common in patients with RLS, and RLS was independently correlated with the PSQI score both in the full cohort (OR = 2.63, CI = 1.60-4.00, p < 0.001) and the CKD group (OR = 2.39, CI = 1.20-4.79, p = 0.014).

Conclusions:

RLS is common in non-dialysis-dependent CKD patients and is an important source of sleep disruption.

Citation:

Lee J; Nicholl DDM; Ahmed SB; Loewen AHS; Hemmelgarn BR; Beecroft JM; Turin TC; Hanly PJ. The prevalence of restless legs syndrome across the full spectrum of kidney disease. J Clin Sleep Med 2013;9(5):455-459.

Is Nocturnal Panic a Distinct Disease Category? Comparison of Clinical Characteristics among Patients with Primary Nocturnal Panic, Daytime Panic, and Coexistence of Nocturnal and Daytime Panic

Objective:

Many patients with panic disorder (PD) experience nocturnal panic attacks. We investigated the differences in demographic variables and symptom characteristics as well as response to treatment among patients with primary day panic (DP), primary nocturnal panic (NP), and the coexistence of DP and NP (DP/NP), and discuss whether NP is a distinct disease category.

Method:

One hundred one consecutive untreated patients with PD were enrolled and subsequently divided into the NP, DP, and DP/NP groups. The presence of 13 panic attack symptom items as well as scores on the Panic Disorder Severity Scale (PDSS) and the Pittsburgh Sleep Quality Index (PSQI) were compared among the groups. After 3 months of regular treatment, PDSS scores were assessed again to evaluate treatment response.

Results:

Nocturnal panic attacks of the participants were mostly reported to occur in the first tertile of nocturnal sleep. The number of males, onset age, and presence of choking sensation were significantly higher, and the PDSS score was significantly lower in the NP group compared with the other groups. The DP/NP group showed the highest PDSS score, and participants in this group were prescribed the highest doses of medication among all groups. Only diagnostic sub-category was significantly associated with treatment response. The total score for PDSS and PSQI correlated significantly only in the NP group.

Conclusions:

DP/NP could be a severe form of PD, while primary NP could be a relatively mild subcategory that may partially share common pathophysiology with adult type night terror.

Citation:

Nakamura M; Sugiura T; Nishida S; Komada Y; Inoue Y. Is nocturnal panic a distinct disease category? Comparison of clinical characteristics among patients with primary nocturnal panic, daytime panic, and coexistence of nocturnal and daytime panic. J Clin Sleep Med 2013;9(5):461-467.

A Multi-Step Pathway Connecting Short Sleep Duration to Daytime Somnolence, Reduced Attention, and Poor Academic Performance: An Exploratory Cross-Sectional Study in Teenagers

Background:

A multi-step causality pathway connecting short sleep duration to daytime somnolence and sleepiness leading to reduced attention and poor academic performance as the final result can be envisaged. However this hypothesis has never been explored.

Objective:

To explore consecutive correlations between sleep duration, daytime somnolence, attention levels, and academic performance in a sample of school-aged teenagers.

Methods:

We carried out a survey assessing sleep duration and daytime somnolence using the Pediatric Daytime Sleepiness Scale (PDSS). Sleep duration variables included week-days' total sleep time, usual bedtimes, and absolute weekdayto-weekend sleep time difference. Attention was assessed by d2 test and by the coding subtest from the WISC-IV scale. Academic performance was obtained from literature and math grades. Structural equation modeling was used to assess the independent relationships between these variables, while controlling for confounding effects of other variables, in one single model. Standardized regression weights (SWR) for relationships between these variables are reported.

Results:

Study sample included 1,194 teenagers (mean age: 15 years; range: 13-17 y). Sleep duration was inversely associated with daytime somnolence (SWR = -0.36, p < 0.01) while sleepiness was negatively associated with attention (SWR = -0.13, p < 0.01). Attention scores correlated positively with academic results (SWR = 0.18, p < 0.01). Daytime somnolence correlated negatively with academic achievements (SWR = -0.16, p < 0.01). The model offered an acceptable fit according to usual measures (RMSEA = 0.0548, CFI = 0.874, NFI = 0.838). A Sobel test confirmed that short sleep duration influenced attention through daytime somnolence (p < 0.02), which in turn influenced academic achievements through reduced attention (p < 0.002).

Conclusions:

Poor academic achievements correlated with reduced attention, which in turn was related to daytime somnolence. Somnolence correlated with short sleep duration.

Citation:

Perez-Lloret S; Videla AJ; Richaudeau A; Vigo D; Rossi M; Cardinali DP; Perez-Chada D. A multi-step pathway connecting short sleep duration to daytime somnolence, reduced attention, and poor academic performance: an exploratory cross-sectional study in teenagers. J Clin Sleep Med 2013;9(5):469-473.

Validation of the Mayo Sleep Questionnaire to Screen for REM Sleep Behavior Disorder in a Community-Based Sample

Objective:

To validate a questionnaire focused on REM sleep behavior disorder (RBD) in a community-based sample.

Background:

RBD is a parasomnia manifested by recurrent dream enactment behavior during REM sleep. While confirmation of RBD requires the presence of REM sleep without atonia on polysomnography (PSG), a screening measure for RBD validated in older adults would be desirable for clinical and research purposes.

Methods:

We had previously developed the Mayo Sleep Questionnaire (MSQ) to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of subjects' bed partners with the findings on PSG. All subjects recruited from 10/04 to 12/08 in the Mayo Clinic Study of Aging—a population-based study of aging in Olmsted County, Minnesota—who had also undergone a previous PSG were the focus of this analysis.

Results:

The study sample included 128 subjects (104 male; median age 77 years [range 67-90]), with the following clinical diagnoses at baseline assessment: normal (n = 95), mild cognitive impairment (n = 30), and mild Alzheimer disease (n = 3). Nine (5%) subjects had RBD based on history and PSG evidence of REM sleep without atonia. The core question on recurrent dream enactment behavior yielded sensitivity (SN) of 100% and specificity (SP) of 95% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD improved specificity.

Conclusions:

These data suggest that the MSQ has adequate SN and SP for the diagnosis of RBD among elderly subjects in a community-based sample.

Citation:

Boeve BF; Molano JR; Ferman TJ; Lin Siong-Chi; Bieniek K; Tippmann-Peikert M; Boot B; St. Louis EK; Knopman DS; Petersen RC; Silber MH. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med 2013;9(5):475-480.

Sensitivity and Specificity of Polysomnographic Criteria for Defining Insomnia

Study Objectives:

In recent years, polysomnography-based eligibility criteria have been increasingly used to identify candidates for insomnia research, and this has been particularly true of studies evaluating pharmacologic therapy for primary insomnia. However, the sensitivity and specificity of PSG for identifying individuals with insomnia is unknown, and there is no consensus on the criteria sets which should be used for participant selection. In the current study, an archival data set was used to test the sensitivity and specificity of PSG measures for identifying individuals with primary insomnia in both home and lab settings. We then evaluated the sensitivity and specificity of the eligibility criteria employed in a number of recent insomnia trials for identifying primary insomnia sufferers in our sample.

Design:

Archival data analysis.

Settings:

Study participants' homes and a clinical sleep laboratory.

Participants:

Adults: 76 with primary insomnia and 78 non-complaining normal sleepers.

Measurements and Results:

ROC and cross-tabs analyses were used to evaluate the sensitivity and specificity of PSG-derived total sleep time, latency to persistent sleep, wake after sleep onset, and sleep efficiency for discriminating adults with primary insomnia from normal sleepers. None of the individual criteria accurately discriminated PI from normal sleepers, and none of the criteria sets used in recent trials demonstrated acceptable sensitivity and specificity for identifying primary insomnia.

Conclusions:

The use of quantitative PSG-based selection criteria in insomnia research may exclude many who meet current diagnostic criteria for an insomnia disorder.

Citation:

Edinger JD; Ulmer CS; Means MK. Sensitivity and specificity of polysomnographic criteria for defining insomnia. J Clin Sleep Med 2013;9(5):481-491.

C-Reactive Protein and Carotid Intima-Media Thickness in Children with Sleep Disordered Breathing

Study Objectives:

Obesity is a risk factor for sleep disordered breathing (SDB) in children. Plasma levels of high-sensitivity C-reactive protein (Hs-CRP) are predictive of cardiovascular morbidity in adults, and CRP levels are associated with over-weight. Increased carotid intima-media thickness (IMT) is associated with several cardiovascular risk factors. We evaluated the effect of SDB on CRP levels and IMT in lean and obese children not selected for snoring.

Methods:

101 children (age 5-15 years) attending a weight clinic or scheduled for routine visit. IMT was measured with quantitative B-mode ultrasound scans. The apnea-hypopnea index (AHI) was measured overnight: AHI < 1 defined controls, AHI ≥ 1 to < 5 = mild SDB, and AHI ≥ 5 = obstructive sleep apnea (OSA).

Results:

AHI was significantly associated with Hs-CRP concentration (r = 0.32, p = 0.002) in all 101 children irrespective of age and sex. Body mass index (BMI) was higher in OSA children than controls (25.5 ± 7.0 vs 22.1 ± 6.9, p = 0.05). Obese children had 3.3 times more probability of having OSA (HR 3.3, 95% CI 1.2-9.3, p = 0.02) than lean children.

Hs-CRP values were significantly higher in children with OSA than in children without (p = 0.011), but not when BMI z-score was added as covariate. IMT was not associated with AHI or SDB.

Conclusions:

The results of this study suggest an association between OSA and Hs-CRP concentrations (mainly mediated by overweight and obesity), but not between OSA and subclinical atherosclerosis. There is scope for prevention in childhood before OSA syndrome causes the irreversible damage to arteries observed in adult patients.

Citation:

Iannuzzi A; Licenziati MR; De Michele F; Verga MC; Santoriello C; Di Buono L; Renis M; Lembo L; D'Agostino B; Cappetta D; Polverino M; Polverino F. C-reactive protein and carotid intima-media thickness in children with sleep disordered breathing. J Clin Sleep Med 2013;9(5):493-498.

Nocturnal Temazepam in the Treatment of Narcolepsy

Narcolepsy is characterized by fragmented nighttime sleep and frequent arousals. One treatment approach to improve daytime symptoms is to consolidate nighttime sleep through decreasing arousals. Sodium oxybate is the first FDA-approved medication that follows this approach. Benzodiazepines are known to also decrease arousals at night and have been proposed to help with sleep fragmentation. In one report, clonazepam was shown to improve cataplexy in 10 of 14 patients with narcolepsy although no improvement in daytime sleepiness was reported. The purpose of this case review was to share our experience of nocturnal temazepam on daytime sleepiness in patients with narcolepsy as measured by the Epworth Sleepiness Scale (ESS).

Citation:

Kansagra S; Walter R; Vaughn B. Nocturnal temazepam in the treatment of narcolepsy. J Clin Sleep Med 2013;9(5):499-500.

Sleep Disturbance in Pediatric PTSD: Current Findings and Future Directions

Many studies have provided strong evidence of a fundamental and complex role for sleep disturbances in adult posttraumatic stress disorder (PTSD). Investigations of adult PTSD using subjective and objective measures document sleep architecture abnormalities and high prevalence of sleep disordered breathing, periodic limb movement disorder, nightmares, and insomnia. PTSD treatment methods do appear to significantly improve sleep disturbance, and also studies suggest that treatments for sleep disorders often result in improvements in PTSD symptoms. Further, the most recent evidence suggests sleep abnormalities may precede the development of PTSD. Given the importance of sleep disorders to the onset, course, and treatment of adult PTSD, examination of sleep disturbances far earlier in the life course is imperative. Here we review the literature on what we know about sleep disturbances and disorders in pediatric PTSD. Our review indicates that the extant, empirical data examining sleep disturbance and disorders in pediatric PTSD is limited. Yet, this literature suggests there are significantly higher reports of sleep disturbances and nightmares in children and adolescents exposed to trauma and/or diagnosed with PTSD than in non-trauma-exposed samples. Sleep questionnaires are predominantly employed to assess sleep disorders in pediatric PTSD, with few studies utilizing objective measures. Given the important, complex relationship being uncovered between adult PTSD and sleep, this review calls for further research of sleep in children with PTSD using more specific subjective measures and also objective measures, such as polysomnography and eventually treatment trial studies.

Citation:

Kovachy B; O'Hara R; Hawkins N; Gershon A; Primeau MM; Madej J; Carrion V. Sleep disturbance in pediatric PTSD: current findings and future directions. J Clin Sleep Med 2013;9(5):501-510.

Normal Ferritin in a Patient with Iron Deficiency and RLS

CPAP and Cognition in OSA (APPLES)

Vitamin D Deficiency, Excessive Daytime Sleepiness: An Epiphenomenon or a “Chicken or an Egg—Which Came First” Issue?

We've Only Just Begun: A Conversation Started Shouldn't Be Mistaken for The Last Word

Foundations of Psychiatric Sleep Medicine