Simplified sleep restriction for insomnia in general practice: a randomised controlled trial

Background

Insomnia is common in primary care. Cognitive behavioural therapy for insomnia (CBT-I) is effective but requires more time than is available in the general practice consultation. Sleep restriction is one behavioural component of CBT-I.

Aim

To assess whether simplified sleep restriction (SSR) can be effective in improving sleep in primary insomnia.

Design and setting

Randomised controlled trial of patients in urban general practice settings in Auckland, New Zealand.

Method

Adults with persistent primary insomnia and no mental health or significant comorbidity were eligible. Intervention patients received SSR instructions and sleep hygiene advice. Control patients received sleep hygiene advice alone. Primary outcomes included change in sleep quality at 6 months measured by the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and sleep efficiency (SE%). The proportion of participants reaching a predefined ‘insomnia remission’ treatment response was calculated.

Results

Ninety-seven patients were randomised and 94 (97%) completed the study. At 6-month follow-up, SSR participants had improved PSQI scores (6.2 versus 8.4, P<0.001), ISI scores (8.6 versus 11.1, P = 0.001), actigraphy-assessed SE% (difference 2.2%, P = 0.006), and reduced fatigue (difference −2.3 units, P = 0.04), compared with controls. SSR produced higher rates of treatment response (67% [28 out of 42] versus 41% [20 out of 49]); number needed to treat = 4 (95% CI = 2.0 to 19.0). Controlling for age, sex, and severity of insomnia, the adjusted odds ratio for insomnia remission was 2.7 (95% CI = 1.1 to 6.5). There were no significant differences in other outcomes or adverse effects.

Conclusion

SSR is an effective brief intervention in adults with primary insomnia and no comorbidities, suitable for use in general practice.     

Effects of the Melatonin MT-1/MT-2 Agonist Ramelteon on Daytime Body Temperature and Sleep

Study Objectives:

A reduction in core temperature and an increase in the distal-proximal skin gradient (DPG) are reported to be associated with shorter sleep onset latencies (SOL) and better sleep quality. Ramelteon is a melatonin MT-1/MT-2 agonist approved for the treatment of insomnia. At night, ramelteon has been reported to shorten SOL. In the present study we tested the hypothesis that ramelteon would reduce core temperature, increase the DPG, as well as shorten SOL, reduce wakefulness after sleep onset (WASO), and increase total sleep time (TST) during a daytime sleep opportunity.

Design:

Randomized, double-blind, placebo-controlled, cross-over design. Eight mg ramelteon or placebo was administered 2 h prior to a 4-h daytime sleep opportunity.

Setting:

Sleep and chronobiology laboratory.

Participants:

Fourteen healthy adults (5 females), aged (23.2 ± 4.2 y).

Measurements and Results:

Primary outcome measures included core body temperature, the DPG and sleep physiology (minutes of total sleep time [TST], wake after sleep onset [WASO], and SOL). We also assessed as secondary outcomes, proximal and distal skin temperatures, sleep staging and subjective TST. Repeated measures ANOVA revealed ramelteon significantly reduced core temperature and increased the DPG (both P < 0.05). Furthermore, ramelteon reduced WASO and increased TST, and stages 1 and 2 sleep (all P < 0.05). The change in the DPG was negatively correlated with SOL in the ramelteon condition.

Conclusions:

Ramelteon improved daytime sleep, perhaps mechanistically in part by reducing core temperature and modulating skin temperature. These findings suggest that ramelteon may have promise for the treatment of insomnia associated with circadian misalignment due to circadian sleep disorders.

Citation:

Markwald RR; Lee-Choing TL; Burke TM; Snider JA; Wright KP. Effects of the melatonin MT-1/MT-2 agonist ramelteon on daytime body temperature and sleep. SLEEP 2010;33(6):825-831     

Actigraphy in the Assessment of Insomnia: A Quantitative Approach

Study Objective:

The lack of quantitative criteria for identifying insomnia using actigraphy represents an unresolved limit for the use of actigraphy in a clinical setting. The current study was conducted to evaluate the most efficient actigraphic parameter in the assessment of insomnia and to suggest preliminary quantitative actigraphic criteria (QAC).

Participants and Measurements:

Performing a retrospective study we recovered 408 actigraphic records from 3 sleep measure databases: 2 regarding insomnia patients (n = 126) and one normal sleepers (n = 282). We compared the 2 samples analyzing the following actigraphic sleep parameters: time in bed (TIB), sleep onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), sleep efficiency percentage (SE%), number of awakenings longer than 5 minutes (NA > 5) and mean motor activity (MA). Moreover, a linear discriminant function (LDF) was developed to identify and combine the most useful actigraphic sleep parameters to separate insomnia patients from normal sleepers. Using Youden index we calculated the preliminary QAC for each actigraphic sleep parameter and for LDF. Receiver operator characteristic (ROC) curves for classifying the accuracy of QAC were performed.

Results:

All sleep parameters recorded by actigraphy significantly differentiated the 2 groups, except TIB. An LDF analysis showed that the most useful combination of actigraphic sleep parameters to assess insomnia was TST, SOL, and NA > 5, which obtained the best ROC and the best balance between positive and negative predictive values compared to any single actigraphic parameter.

Conclusion:

Actigraphy provided a satisfactory objective measurement of sleep quality in insomnia patients. The combination of TST, SOL, and NA > 5 proved the best way to assess insomnia using actigraphy. Acknowledging that the lack of a technological standard and some methodological limitations prevent us generalizing our results, we recommend additional studies on larger populations using different actigraph models.

Citation:

Natale V; Plazzi G; Martoni M. Actigraphy In The Assessment Of Insomnia: A Quantitative Approach. SLEEP 2009;32(6):767–771.     

Insomnia Did Not Predict Incident Hypertension in Older Adults in the Cardiovascular Health Study

Study Objective:

We hypothesized that the sleep complaints of insomnia predict incident hypertension, particularly in African Americans. The purpose of this study was to analyze insomnia complaints as predictors of incident hypertension in the Cardiovascular Health Study (CHS), stratifying by gender and allowing for race and sleep variable interaction.

Design:

This is a prospective cohort study over a 6-year period of follow-up.

Setting:

This is a community-based study of participants in Forsyth County, North Carolina; Pittsburgh, Pennsylvania; Sacramento County, California; and Washington County, Maryland.

Participants:

The study analyzed data from 1419 older individuals (baseline mean age 73.4 ± 4.4 years) from the Cardiovascular Health Study who were not hypertensive at baseline.

Interventions:

none

Measurements:

We constructed relative risks of incident hypertension over a 6-year period for insomnia complaints singly and in combination.

Results:

Difficulty falling asleep, singly or in combination with other sleep complaints, predicted a statistically significant reduction of risk for incident hypertension for non-African American men in 6 years of follow-up. Insomnia complaints did not predict incident hypertension in 6 years of follow-up in women or in African Americans, although there may not have been enough power to show a significant association for African Americans.

Conclusions:

Insomnia did not predict hypertension in this older cohort which was free of hypertension at baseline. Difficulty falling asleep was associated with reduced risk of hypertension in non-African American men.

Citation:

Phillips B; Bůžková P; Enright P. Insomnia did not predict incident hypertension in older adults in the cardiovascular health study. SLEEP 2009;32(1):65-72.     

Logging on for Better Sleep: RCT of the Effectiveness of Online Treatment for Insomnia

Study Objectives:

Despite effective cognitive behavioral treatments for chronic insomnia, such treatments are underutilized.^1,2 This study evaluated the impact of a 5-week, online treatment for insomnia.

Design:

This was a randomized controlled trial with online treatment and waiting list control conditions.

Participants:

Participants were 118 adults with chronic insomnia.

Setting:

Participants received online treatment from their homes.

Intervention:

Online treatment consisted of psychoeducation, sleep hygiene, and stimulus control instruction, sleep restriction treatment, relaxation training, cognitive therapy, and help with medication tapering.

Measurements and Results:

From pre- to post-treatment, there was a 33% attrition rate, and attrition was related to referral status (i.e., drop-outs were more likely to have been referred for treatment rather than recruited from the community). Using a mixed model analysis of variance procedure (ANOVA), results showed that online treatment produced statistically significant improvements in the primary end points of sleep quality, insomnia severity, and daytime fatigue. Online treatment also produced significant changes in process variables of pre-sleep cognitive arousal and dysfunctional beliefs about sleep.

Conclusions:

Implications of these findings are that identification of who most benefits from online treatment is a worthy area of future study.

Citation:

Vincent N; Lewycky S. Logging on for better sleep: RCT of the effectiveness of online treatment for insomnia. SLEEP 2009;32(6):807-815.     

Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial

Study Objectives:

To evaluate the short-term efficacy and safety of electroacupuncture for the treatment of primary insomnia.

Design:

Randomized, single-blind, placebo-controlled, parallel-group.

Setting:

A university-based sleep clinic.

Participants:

Community sample of 60 Chinese adult volunteers who report having insomnia 3 or more nights per week, whose symptoms meet the DSM-IV criteria for primary insomnia for at least 3 months, and who have an Insomnia Severity Index total score of at least 15. Participants were screened with polysomnography and the Structured Clinical Interview for the DSM-IV prior to randomization.

Intervention:

Electroacupuncture at Yintang (EX-HN3), Baihui (GV20), bilateral ear Shenmen, Sishencong (EX-HN1), and Anmian (EX) 3 times per week for 3 weeks or placebo acupuncture using Streitberger needles at the same points.

Measurements and Results:

Self-reported questionnaires, 1-week sleep diaries, and 3-day actigraphy were collected at baseline and 1 week after treatment. The Insomnia Severity Index was used as the primary outcome measure. Both groups showed significant improvement compared with the pretreatment baseline. One-way analysis of covariance adjusted for baseline scores showed that there were significantly greater improvements in sleep efficiency by sleep diary and actigraphy in the electroacupuncture group. However, no significant between-group differences were observed in the Insomnia Severity Index and other outcome measures. The proportions of subjects having less than 30 minutes of wake after sleep onset and a sleep efficiency of at least 85% at the posttreatment visit were significantly higher in the electroacupuncture group. All adverse events were mild in severity.

Conclusion:

We found a slight advantage of electroacupuncture over placebo acupuncture in the short-term treatment of primary insomnia. Because of some limitations of the current study, further studies are necessary to verify the effectiveness of acupuncture for insomnia.

Citation:

Yeung WF; Chung KF; Zhang SP; Yap TG; Law ACK. Electroacupuncture for primary insomnia: a randomized controlled trial. SLEEP 2009;32(8):1039-1047.     

Efficacy and Safety of 6-Month Nightly Ramelteon Administration in Adults with Chronic Primary Insomnia

Study Objectives:

Long-duration ( ≥ 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT₁/MT₂ melatonin-receptor agonist used for insomnia treatment.

Design:

Six-month, randomized, double-blind, placebo-controlled study.

Setting:

Forty-six investigative sites in the United States, Europe, Russia, and Australia.

Participants:

Four hundred fifty-one adults (age ≥ 18 years) with chronic primary insomnia.

Interventions:

Ramelteon, 8 mg, or placebo 30 minutes before bedtime nightly for 6 months.

Measurements:

Sleep was evaluated by polysomnography and morning questionnaires on the first 2 nights of Week 1; the last 2 nights of Months 1, 3, 5, and 6; and Nights 1 and 2 of the placebo run-out. Next-morning residual effects as well as adverse effects and vital signs were recorded at each visit. Rebound insomnia and withdrawal effects were evaluated during placebo run-out.

Results:

Over the 6 months of treatment, ramelteon consistently reduced latency to persistent sleep compared with baseline and with placebo; significant decreases were observed at Week 1 and Months 1, 3, 5, and 6 (P < 0.05). Ramelteon significantly reduced subjective sleep latency relative to placebo at Week 1, Month 1, and Month 5 (P < 0.05), with reductions nearing statistical significance at Months 3 and 6 (P ≤ 0.08). No significant next-morning residual effects were detected during ramelteon treatment. No withdrawal symptoms or rebound insomnia were detected after ramelteon discontinuation. Most adverse events were mild or moderate in severity.

Conclusions:

In adults with chronic insomnia, long-term ramelteon treatment consistently reduced sleep onset, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.

Citation:

Mayer G; Wang-Weigand S; Roth-Schechter B; Lehmann R; Staner C; Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. SLEEP 2009;32(3):351–360.     

Contribution of cancer symptoms, dysfunctional sleep related thoughts, and sleep inhibitory behaviors to the insomnia process in breast cancer survivors: a daily process analysis

Study Objectives:

Using a comprehensive cognitive-behavioral model of insomnia and a daily process approach, this study was conducted to examine the contribution of cancer symptoms and dysfunctional sleep related thoughts and behaviors to the process of insomnia in breast cancer survivors.

Design:

Within-group longitudinal research design.

Setting:

An academic medical center.

Participants:

41 women with breast cancer who had completed their primary cancer treatment and met Research Diagnostic Criteria for primary insomnia or insomnia comorbid with breast cancer.

Interventions:

NA

Measurements and Results:

For 28 days, participants completed morning diaries assessing sleep, nighttime pain and hot flashes, and dysfunctional sleep related thoughts and behaviors during the day and night, and evening diaries assessing daytime pain, fatigue, hot flashes, and mood. All diaries were collected using an automated telephone-based system. Results revealed that poorer sleep was related to nighttime pain and hot flashes in breast cancer patients. Time-lagged effects were also found. The current study identified higher levels of dysfunctional sleep related thoughts and sleep inhibitory behaviors during the day and night as antecedents of insomnia, and higher levels of pain, fatigue, and hot flashes and lower levels of positive mood and dysfunctional sleep related thoughts as consequences of insomnia in this population.

Conclusions:

The current study found support for a comprehensive cognitive-behavioral model of insomnia, which has several theoretical, practice, and research implications.

Citation:

Rumble ME; Keefe FJ; Edinger JD; Affleck G; Marcom PK; Shaw HS. Contribution of cancer symptoms, dysfunctional sleep related thoughts, and sleep inhibitory behaviors to the insomnia process in breast cancer survivors: a daily process analysis. SLEEP 2010;33(11):1501-1509.     

Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week Sleep Laboratory and Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia

Study Objectives:

To evaluate the efficacy and safety of doxepin 1 mg and 3 mg in elderly subjects with chronic primary insomnia.

Design and Methods:

The study was a randomized, double-blind, parallel-group, placebo-controlled trial. Subjects meeting DSM-IV-TR criteria for primary insomnia were randomized to 12 weeks of nightly treatment with doxepin (DXP) 1 mg (n = 77) or 3 mg (n = 82), or placebo (PBO; n = 81). Efficacy was assessed using polysomnography (PSG), patient reports, and clinician ratings. Objective efficacy data are reported for Nights (N) 1, 29, and 85; subjective efficacy data during Weeks 1, 4, and 12; and Clinical Global Impression (CGI) scale and Patient Global Impression (PGI) scale data after Weeks 2, 4, and 12 of treatment. Safety assessments were conducted throughout the study.

Results:

DXP 3 mg led to significant improvement versus PBO on N1 in wake time after sleep onset (WASO; P < 0.0001; primary endpoint), total sleep time (TST; P < 0.0001), overall sleep efficiency (SE; P < 0.0001), SE in the last quarter of the night (P < 0.0001), and SE in Hour 8 (P < 0.0001). These improvements were sustained at N85 for all variables, with significance maintained for WASO, TST, overall SE, and SE in the last quarter of the night. DXP 3 mg significantly improved patient-reported latency to sleep onset (Weeks 1, 4, and 12), subjective TST (Weeks 1, 4, and 12), and sleep quality (Weeks 1, 4, and 12). Several global outcome-related variables were significantly improved, including the severity and improvement items of the CGI (Weeks 2, 4, and 12), and all 5 items of the PGI (Week 12; 4 items after Weeks 2 and 4). Significant improvements were observed for DXP 1 mg for several measures including WASO, TST, overall SE, and SE in the last quarter of the night at several time points. Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects; additionally, there were no reports of memory impairment, complex sleep behaviors, anticholinergic effects, weight gain, or increased appetite.

Conclusions:

DXP 1 mg and 3 mg administered nightly to elderly chronic insomnia patients for 12 weeks resulted in significant and sustained improvements in most endpoints. These improvements were not accompanied by evidence of next-day residual sedation or other significant adverse effects. DXP also demonstrated improvements in both patient- and physician-based ratings of global insomnia outcome. The efficacy of DXP at the doses used in this study is noteworthy with respect to sleep maintenance and early morning awakenings given that these are the primary sleep complaints of the elderly. This study, the longest placebo-controlled, double-blind, polysomnographic trial of nightly pharmacotherapy for insomnia in the elderly, provides the best evidence to date of the sustained efficacy and safety of an insomnia medication in older adults.

Citation:

Krystal AD; Durrence HH; Scharf M; Jochelson P; Rogowski R; Ludington E; Roth T. Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. SLEEP 2010;33(11):1553-1561.     

Insomnia with Objective Short Sleep Duration is Associated with Deficits in Neuropsychological Performance: A General Population Study

Study Objectives:

To examine the joint effect of insomnia and objective short sleep duration on neuropsychological performance.

Design:

Representative cross-sectional study.

Setting:

Sleep laboratory.

Participants:

1,741 men and women randomly selected from central Pennsylvania.

Interventions:

None.

Measurements:

Insomnia (n = 116) was defined by a complaint of insomnia with a duration ≥ 1 year and the absence of sleep disordered breathing (SDB), while normal sleep (n = 562) was defined as the absence of insomnia, excessive daytime sleepiness, and SDB. Both groups were split according to polysomnographic sleep duration into 2 categories: ≥ 6 h of sleep (“normal sleep duration”) and < 6 h of sleep (“short sleep duration”). We compared the groups'' performance on a comprehensive neuropsychological battery that measured processing speed, attention, visual memory, and verbal fluency, while controlling for age, race, gender, education, body mass index, and physical and mental health.

Results:

No significant differences were detected between insomniacs and controls. However, the insomnia with short sleep duration group compared to the control with normal or short sleep duration groups showed poorer neuropsychological performance in variables such as processing speed, set-switching attention, and number of visual memory errors and omissions. In contrast, the insomnia with normal sleep duration group showed no significant deficits.

Conclusions:

Insomnia with objective short sleep duration is associated with deficits in set-switching attentional abilities, a key component of the “executive control of attention.” These findings suggest that objective sleep duration may predict the severity of chronic insomnia, including its effect on neurocognitive function.

Citation:

Fernandez-Mendoza J; Calhoun S; Bixler EO; Pejovic S; Karataraki M; Liao D; Vela-Bueno A; Ramos-Platon MJ; Sauder KA; Vgontzas AN. Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study. SLEEP 2010;33(4):459-465.     

The Multidimensional Correlates Associated With Short Nocturnal Sleep Duration and Subjective Insomnia Among Taiwanese Adolescents

Study Objectives:

The aim of this study was to examine the correlates associated with short nocturnal sleep duration and subjective insomnia, including individual factors, family factors, peer factors, school factors, and the problematic use of high-tech devices among a large-scale representative population of Taiwanese adolescents.

Design:

Cross-sectional study.

Setting:

A total of 23 junior high and 29 senior high/vocational schools were randomly selected across southern Taiwan.

Participants:

Eight thousand four adolescent students.

Interventions:

N/A.

Measurements and Results:

The multidimensional correlates associated with short nocturnal sleep duration and subjective insomnia were examined using χ² automatic interaction detection analysis and logistic regression analysis models. The results indicated that an older age, self-reported depression, being in the third year of school, drinking coffee at night, and problematic Internet use were significantly associated with short nocturnal sleep duration in adolescents. Furthermore, self-reported depression, low school affinity, high family conflict, low connectedness to their peer group, and problematic Internet use were associated with subjective insomnia in adolescents.

Conclusions:

The results of this study indicate that a variety of individual, family, peer, and school factors were associated with short nocturnal sleep duration and subjective insomnia in adolescents. Furthermore, the correlates of short sleep duration were not identical to those of subjective insomnia. Parents and health professionals should be wary of sleep patterns among adolescents who have the identified correlates of short nocturnal sleep duration and subjective insomnia.

Citation:

Yen CF; Ko CH; Yen JY; Cheng CP. The multidimensional correlates associated with short nocturnal sleep duration and subjective insomnia among Taiwanese adolescents. SLEEP 2008;31(11):1515–1525.     

The Utility of Single-Channel Nasal Airflow Pressure Transducer in the Diagnosis Of OSA at Home

Rationale:

Given the high prevalence of obstructive sleep apnea (OSA) and the demand on polysomnography (PSG), there is a need for low cost accurate simple diagnostic modalities that can be easily deployed in primary care to improve access to diagnosis.

Study Objectives:

The aim was to examine the utility of single-channel nasal airflow monitoring using a pressure transducer at home in patients with suspected OSA.

Design:

Cross-sectional study

Setting:

Laboratory and home

Participants:

The study was conducted in two populations. Consecutive patients with suspected OSA were recruited from the sleep disorders clinic at a tertiary referral center and from 6 local metropolitan primary care centers.

Interventions:

All patients answered questionnaires and had laboratory PSG. Nasal airflow was monitored for 3 consecutive nights at home in random order either before or after PSG.

Results:

A total of 193 patients participated (105 sleep clinic patients and 88 from primary care). The mean bias PSG apnea hypopnea index (AHI) minus nasal flow respiratory disturbance index (NF RDI) was –4.9 events per hour with limits of agreement (2 SD) of 27.8. NF RDI monitored over 3 nights had high accuracy for diagnosing both severe OSA (defined as PSG AHI > 30 events per hour) with area under the receiver operating characteristic curve (AUC) 0.92 (95% confidence interval (CI) 0.88-0.96) and any OSA (PSG AHI >5), AUC 0.87 (95% CI 0.80-0.94).

Conclusions:

Single-channel nasal airflow can be implemented as an accurate diagnostic tool for OSA at home in both primary care and sleep clinic populations.

Citation:

Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. The utility of single-channel nasal airflow pressure transducer in the diagnosis of OSA at home. SLEEP 2010;33(8):1097-1105.     

Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea: systematic review and meta-analysis

Context:

Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle crash.

Objective:

We performed a systematic review of the literature concerning the impact of continuous positive airway pressure (CPAP) treatment on motor vehicle crash risk among drivers with OSA. The primary objective was to determine whether CPAP use could reduce the risk of motor vehicle crash among drivers with OSA. A secondary objective involved determining the time on treatment required for CPAP to improve driver safety.

Data Sources:

We searched seven electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) and the reference lists of all obtained articles.

Study Selection:

We included studies (before-after, case-control, or cohort) that addressed the stated objectives. We evaluated the quality of each study and the interplay between the quality, quantity, robustness, and consistency of the evidence. We also tested for publication bias.

Data Extraction:

Data were extracted by two independent analysts. When appropriate, data were combined in a fixed or random effects meta-analysis.

Results:

A meta-analysis of 9 observational studies examining crash risk of drivers with OSA pre- vs. post-CPAP found a significant risk reduction following treatment (risk ratio = 0.278, 95% CI: 0.22 to 0.35; P < 0.001). Although crash data are not available to assess the time course of change, daytime sleepiness improves significantly following a single night of treatment, and simulated driving performance improves significantly within 2 to 7 days of CPAP treatment.

Conclusions:

Observational studies indicate that CPAP reduces motor vehicle crash risk among drivers with OSA.

Citation:

Tregear S; Reston J; Schoelles K; Phillips B. Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea. SLEEP 2010;33(10):1373-1380.     

Brain Activation Changes Before and After PAP Treatment in Obstructive Sleep Apnea

Study Objectives:

Obstructive sleep apnea syndrome (OSAS) is associated with cognitive and functional deficits, most of which are corrected after positive airway pressure (PAP) treatment. Previous studies investigating the neural underpinnings of OSAS failed to provide consistent results both on the cerebral substrates underlying cognitive deficits and on the effect of treatment on these anomalies. The aims of the study were a) to investigate whether never-treated OSA patients demonstrated differences in brain activation compared to healthy controls during a cognitive task; and b) to investigate whether any improvements in cognitive functioning found in OSA patients after treatment reflected a change in the underlying cerebral activity.

Design:

OSA patients and healthy controls underwent functional magnetic resonance imaging (fMRI) scanning. They were compared on performance and brain activation during a 2-back working-memory task. Patients were also re-evaluated after 3 months treatment with PAP. Cognitive functions were evaluated using neurocognitive tests. Sleepiness (ESS), mood (Beck Depression Inventory) and, quality-of-life (SF-36) were also assessed.

Setting:

The Sleep Disorders Center and CERMAC at the Vita-Salute San Raffaele University.

Patients or Participants:

17 OSA patients and 15 age- and education-matched healthy controls.

Interventions:

PAP treatment for 3 months.

Measurements and Results:

Compared to controls, never-treated OSA patients showed increased activations in the left frontal cortex, medial precuneus, and hippocampus, and decreased activations in the caudal pons. OSA patients showed decreases in activation with treatment in the left inferior frontal gyrus and anterior cingulate cortex, and bilaterally in the hippocampus. Most neurocognitive domains, impaired at baseline, showed significant improvement after treatment.

Conclusions:

OSA patients showed an overrecruitment of brain regions compared to controls, in the presence of the same level of performance on a working-memory task. Decreases of activation in prefrontal and hippocampal structures were observed after treatment in comparison to baseline. These findings may reflect a neural compensation mechanism in never-treated patients, which is reduced by effective treatment.

Citation:

Castronovo V; Canessa N; Ferini Strambi L; Aloia MS; Consonni M; Marelli S; Iadanza A; BruschiA; Falini A; Cappa SF. Brain activation changes before and after PAP treatment in obstructive sleep apnea. SLEEP 2009;32(9):1161-1172.     

Behavioral Correlates of Sleep-Disordered Breathing in Older Men

Study Objectives:

To examine the association between sleep-disordered breathing (SDB) and subjective measures of daytime sleepiness, sleep quality, and sleep-related quality of life in a large cohort of community-dwelling older men and to determine whether any association remained after adjustment for sleep duration.

Design:

Cross-sectional. The functional outcome measures of interest were daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep-related symptoms (Pittsburgh Sleep Quality Index, PSQI), and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ). Analysis of variance and adjusted regression analyses examined the association between these outcome measures and SDB severity and actigraphy-determined total sleep time (TST). We then explored whether associations with SDB were confounded by sleep duration by adjusting models for TST.

Setting:

Community-based sample in home and research clinic settings.

Participants:

Two-thousand eight-hundred forty-nine older men from the multicenter Osteoporotic Fractures in Men Study that began in 2000. All participants underwent in-home polysomnography for 1 night and wrist actigraphy for a minimum of 5 consecutive nights.

Interventions:

N/A.

Measurements and Results:

Participants were aged 76.4 ± 5.5 years and had an apnea-hypopnea index (AHI) of 17.0 ± 15.0. AHI and TST were weakly correlated. ESS scores individually were modestly associated with AHI and TST, but the association with AHI was attenuated by adjustment for TST. PSQI and FOSQ scores were largely not associated with measures of SDB severity but were modestly associated with TST.

Conclusions:

Daytime sleepiness, nighttime sleep disturbances, and sleep-related quality of life were modestly associated with TST. After adjustment for TST, there was no independent association with SDB severity. These results underscore the potential differences in SDB functional outcomes in older versus young and middle-aged adults.

Citation:

Kezirian EJ; Harrison SL; Ancoli-Israel S; Redline S; Ensrud K; Goldberg AN; Claman DM; Spira AP; Stone KL. Behavioral correlates of sleep-disordered breathing in older men. SLEEP 2009;32(2):253–261.     

A comparison of insomnia and depression as predictors of disability pension: the HUNT Study

Study Objectives:

Depression and insomnia are common and frequently comorbid. Unlike the priority now accorded to depression, insomnia is comparatively ignored as a reason for impaired occupational functioning. The objective of this study was to compare their relative impact upon medically certified disability pension award.

Design:

Historical cohort study

Setting:

Data from a population-based health survey in Nord-Trøndelag County in Norway (HUNT-2) was linked with a comprehensive national social security database.

Participants:

Participants within working age (20-66 years of age) not claiming disability pension (N = 37,302).

Interventions:

N/A

Measurements and Results:

We compared complaints of insomnia and depression as predictors of disability pension award 18–48 months after a health survey. Insomnia complaints and depression each were similarly associated with disability pension award after adjustment for multiple health and sociodemographic factors, with similar odds ratios (1.66 [1.37–2.01] and 1.56 [1.24–1.96] respectively). Comorbidity did not contribute to disability beyond that expected from each condition. Taking the higher prevalence of insomnia complaints into account, insomnia complaints contributed as much or even more than depression to work-related disability.

Conclusions:

Depression is regarded as a major contributor to work disability and is increasingly the primary diagnosis in disability pension award. Our results suggest that although rarely reported in official registries of disability pension causes, insomnia has an equally important and independent role, particularly among the younger group. This suggests that this potentially treatable factor has considerable economic impact and should receive more attention in clinical and public health management.

Citation:

Overland S; Glozier N; Sivertsen B; Stewart R; Neckelmann D; Krokstad S; Mykletun A. A Comparison of Insomnia and Depression as Predictors of Disability Pension: The HUNT Study. SLEEP 2008;31(6):875-880.     

The Impact of Sleep-Related Attentional Bias on Polysomnographically Measured Sleep in Primary Insomnia

Study Objectives:

Although sleep-related attentional bias has been shown to be evident in primary insomnia, the association with objectively measured sleep has not been investigated. In the present study, we used polysomnography (PSG) to fill this void.

Design:

Patients with primary insomnia and healthy controls were studied using a visual dot probe task (VDP) and an emotional Stroop task (EST). Additionally, polysomnography was carried out in a sub-sample (n = 22) of patients in the subsequent night.

Setting:

Department of Psychiatry and Psychotherapy of the University of Freiburg Medical Center.

Participants:

Thirty patients with primary insomnia and 30 matched healthy controls.

Interventions:

N/A

Measurements and Results:

Patients with primary insomnia demonstrated a significant sleep-related attentional bias compared to controls in the EST but no significant group effects were found for the VDP. VDP attentional bias scores were positively correlated with measures of sleep pressure, including total sleep time, sleep efficiency, and the amount of slow wave sleep. EST attentional bias scores were not correlated with subsequent PSG parameters, and we did not observe a correlation between attentional bias scores on the two tasks.

Conclusions:

The unexpected relationship between increased attentional bias, in the VDP task, and improved markers of sleep duration and continuity, may be indicative of a homeostatic craving for sleep in those with high attentional bias. This awaits further testing in multiple night studies, to shed light on the mechanisms and implications of sleep-related attentional bias.

Citation:

Spiegelhalder K; Kyle SD; Feige B; Prem M; Nissen C; Espie CA; Riemann D. The impact of sleep-related attentional bias on polysomnographically measured sleep in primary insomnia. SLEEP 2010;33(1):107-112.     

Insomnia with Short Sleep Duration and Mortality: The Penn State Cohort

Study Objectives:

Because insomnia with objective short sleep duration is associated with increased morbidity, we examined the effects of this insomnia subtype on all-cause mortality.

Design:

Longitudinal.

Setting:

Sleep laboratory.

Participants:

1,741 men and women randomly selected from Central Pennsylvania.

Measurements:

Participants were studied in the sleep laboratory and were followed-up for 14 years (men) and 10 years (women). “Insomnia” was defined by a complaint of insomnia with duration ≥ 1 year. “Normal sleeping” was defined as absence of insomnia. Polysomnographic sleep duration was classified into two categories: the “normal sleep duration group” subjects who slept ≥ 6 h and the “short sleep duration group” subjects who slept < 6 h. We adjusted for age, race, education, body mass index, smoking, alcohol, depression, sleep disordered breathing, and sampling weight.

Results:

The mortality rate was 21% for men and 5% for women. In men, mortality risk was significantly increased in insomniacs who slept less than 6 hours compared to the “normal sleep duration, no insomnia” group, (OR = 4.00, CI 1.14-13.99) after adjusting for diabetes, hypertension, and other confounders. Furthermore, there was a marginally significant trend (P = 0.15) towards higher mortality risk from insomnia and short sleep in patients with diabetes or hypertension (OR = 7.17, 95% CI 1.41-36.62) than in those without these comorbid conditions (OR = 1.45, 95% CI 0.13-16.14). In women, mortality was not associated with insomnia and short sleep duration.

Conclusions:

Insomnia with objective short sleep duration in men is associated with increased mortality, a risk that has been underestimated.

Citation:

Vgontzas AN; Liao D; Pejovic S; Calhoun S; Karataraki M; Basta M; Fernández-Mendoza J; Bixler EO. Insomnia with short sleep duration and mortality: the Penn State Cohort. SLEEP 2010;33(9):1159-1164.     

Prospective Trial of Efficacy and Safety of Ondansetron and Fluoxetine in Patients with Obstructive Sleep Apnea Syndrome

Study Objective:

Incremental withdrawal of serotonin during wake to sleep transition is postulated as a key mechanism that renders the pharyngeal airway collapsible. While serotonin promotion with reuptake inhibitors have demonstrated modest beneficial effects during NREM sleep on obstructive sleep apnea (OSA), animal studies suggest a potential therapeutic role for selective serotonin receptor antagonists (5-HT₃) in REM sleep. We aimed to test the hypothesis that a combination of ondansetron (Ond) and fluoxetine (Fl) may effectively reduce expression of disordered breathing during REM and NREM sleep in patients with OSA.

Design and Setting:

A prospective, parallel-groups, single-center trial in patients with OSA.

Participants:

35 adults with apnea hypopnea index (AHI) > 10; range 10-98.

Intervention:

Subjects were randomized to placebo, n = 7; Ond (24 mg QD), n = 9; Fl (5 mg QD) + Ond (12 mg QD), n = 9; and Fl (10 mg QD) + Ond (24 mg QD), n = 10.

Measurements and Results:

AHI was measured by in-lab polysomnography after a 7-day no-treatment period (Baseline) and on days 14 and 28 of treatment. The primary endpoint was AHI reduction at days 14 and 28. OND+FL resulted in approximately 40% reduction of baseline AHI at days 14 and 28 (unadjusted P < 0.03 for each) and improved oximetry trends. This treatment-associated relative reduction in AHI was also observed in REM and supine sleep.

Conclusions:

Combined treatment with OND+FL is well-tolerated and reduces AHI, yielding a potentially therapeutic response in some subjects with OSA.

Citation:

Prasad B; Radulovacki M; Olopade C; Herdegen JJ; Logan T; Carley DW. Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome. SLEEP 2010;33(7):982-989.     

Comparison between a Single-Channel Nasal Airflow Device and Oximetry for the Diagnosis of Obstructive Sleep Apnea

Rationale:

The most common single channel devices used for obstructive sleep apnea (OSA) screening are nasal airflow and oximetry. No studies have directly compared their role in diagnosing OSA at home.

Study Objectives:

To prospectively compare the diagnostic utility of home-based nasal airflow and oximetry to attended polysomnography (PSG) and to assess the diagnostic value of adding oximetry to nasal airflow for OSA.

Design:

Cross-sectional study

Setting:

Laboratory and home

Participants:

Sleep clinic patients with suspected OSA.

Interventions:

All patients had laboratory PSG and 2 sets of 3 consecutive nights on each device; nasal airflow (Flow Wizard, DiagnoseIT, Australia) and oximetry (Radical Set, Masimo, USA) at home in random order.

Results:

Ninety-eight of the 105 patients enrolled completed home monitoring. The accuracy of nasal airflow respiratory disturbance index (NF RDI) was not different from oximetry (ODI 3%) for diagnosing OSA (area under the ROC curve (AUC) difference, 0.04; 95% CI of difference −0.05 to 0.12; P = 0.43) over 3 nights of at-home recording. The accuracy of NF RDI was higher after 3 nights compared to one night (AUC difference, 0.05; 95% CI of difference, 0.01 to 0.08; P = 0.04). Addition of oximetry to nasal airflow did not increase the accuracy for predicting OSA compared to nasal airflow alone (P > 0.1).

Conclusions:

Nasal flow and oximetry have equivalent accuracy for diagnosing OSA in the home setting. Choice of device for home screening of sleep apnea may depend on logistical and service delivery issues.

Citation:

Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. Comparison between a single-channel nasal airflow device and oximetry for the diagnosis of obstructive sleep apnea. SLEEP 2010;33(8):1106-1114.