Sleep restriction therapy and hypnotic withdrawal versus sleep hygiene education in hypnotic using patients with insomnia.

STUDY OBJECTIVES: Insomnia is a common problem that affects 9% to 15% of the population chronically. The primary objective of this study was to demonstrate that 8 weekly sessions of sleep restriction therapy of insomnia combined with hypnotic reduction instructions following a single session of sleep hygiene education would result in greater improvements in sleep and hypnotic use than sleep hygiene education alone. METHODS: Forty-six men and women were recruited from a sleep medicine practice and randomly assigned to sleep hygiene education plus 8 weeks of sleep restriction and hypnotic withdrawal (SR+HW; n = 24), or a sleep hygiene education alone (SHE; n = 22) condition. Pre-randomization, all patients received a single session of instruction in good sleep habits (sleep hygiene education). RESULTS: The SR+HW condition had greater improvements in hypnotic medication usage, sleep onset latency, morning wake time, sleep efficiency, and wake time after sleep onset (trend), than the SHE condition. Continued improvement was seen in TST in the SR+HW group at 6-month follow-up, and gains on all other variables were maintained at 6- and 12-month follow-up. CONCLUSIONS: These results provide evidence that more intensive treatment of insomnia (i.e., 8 sessions of SR+HW plus hypnotic withdrawal instructions) results in better outcomes than SHE alone.

The Time of Day Sleepiness Scale to assess differential levels of sleepiness across the day.

OBJECTIVE: The study evaluated the Time of Day Sleepiness Scale (ToDSS) to determine subjective estimates of sleepiness in the morning, afternoon, and evening. Scores on the ToDSS were compared to the Epworth Sleepiness Scale (ESS). The ToDSS was evaluated on three cohorts of patients at a sleep medicine clinic. METHOD: The items of the ToDSS are modified from the ESS to enable subjective assessment in the morning (before noon), afternoon (noon to 1800 h), and evening (after 1800 h). The scale takes about 5 min to complete. For each item, patients provide an estimate of their level of sleepiness in three separate columns, each indicating the time of day (morning, afternoon, and evening). RESULTS: Each ToDSS score evidenced a one factor structure. The ToDSS enabled the assessment of differential levels of sleepiness across the day among several cohorts, with scores increasing in the afternoon and evening. The ESS and each score of the ToDSS demonstrated high correlations. Lower subjective estimates of sleepiness were documented after treatment with continuous positive airway pressure. CONCLUSIONS: The ToDSS was shown to have comparable psychometric features to the ESS and provided perceived sleepiness levels across the day in an efficient and cost-effective manner. It also enabled characterization of treatment response among a cohort of patients with obstructive sleep apnea.

Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults.

BACKGROUND: Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) experience excessive sleepiness (ES) that might not resolve with nasal continuous positive airway pressure (nCPAP) treatment. OBJECTIVE: The aim of the present study was to assess the efficacy and tolerability of armodafinil 150 or 250 mg QD when used as adjunctive treatment for residual ES associated with OSA/HS in patients who are adherent to nCPAP therapy. METHODS: This 12-week, multicenter, double-blind, randomized, placebo-controlled study was conducted at 37 centers in the United States and Canada. Male and female patients aged 18 to 65 years with residual ES associated with OSA/HS were enrolled. Patients were randomly assigned to receive armodafinil 150 or 250 mg or placebo PO QD for 12 weeks. Assessments were conducted at baseline and study weeks 4, 8, and 12 and included the Maintenance of Wakefulness Test (MWT) to determine wakefulness, the Clinical Global Impression of Change (CGI-C) to determine improvement in clinical condition, the Epworth Sleepiness Scale (ESS) to determine patient-estimated wakefulness, the Brief Fatigue Inventory (BFI) to determine global fatigue, and the Cognitive Drug Research computerized assessment battery. To distinguish between earlier and later effects, sleep latencies, assessed using the MWT, were averaged across the first 4 (9 and 11 AM, and 1 and 3 PM) and last 3 (3, 5, and 7 PM) tests. Tolerability assessments included monitoring of adverse events (AEs), clinical laboratory tests, vital sign measurements, and electrocardiography. RESULTS: A total of 395 patients were enrolled in the study (armodafinil 150 mg/d, 133; armodafinil 250 mg/d, 131; placebo, 131); 392 received >or=1 dose of study drug (armodafinil 150 mg/d, 131; armodafinil 250 mg/d, 131; placebo, 130). The armodafinil and placebo groups were well matched with regard to age (mean [SD], 49.2 [8.9] vs 50.1 [9.4] years), sex (71 vs 69% men), race (84% vs 87% white), and body weight (mean [SD], 110.3 [24.9] vs 111.9 [24.0] kg). At the final visit, the mean (SD) change from baseline in MWT sleep latency across the morning and afternoon was significantly greater in the armodafinil combined group compared with the placebo group (+1.9 [7.3] vs 1.7 [8.6] minutes; P < 0.001). Also at the final visit, the proportions of patients who showed at least minimal improvement on the CGI-C, and the mean (SD) changes from baseline in ESS and BFI scores, were significantly greater in the armodafinil group compared with those in the placebo group (72% vs 37%, -5.5 [5.0] vs -3.3 [4.7], and -1.2 [2.2] vs -0.6 [2.0], respectively; P < 0.001, P < 0.001, and P < 0.01, respectively). No significant effects on nighttime sleep, as assessed using polysomnography, were found with armodafinil. AEs reported in the armodafinil combined and placebo groups were headache, nausea, insomnia, anxiety, and dizziness. Serious AEs (ulcerative colitis, migraine, worsening of Axis II and mood disorder, and duodenal ulcer) were reported in 4 (1.5%) patients receiving armodafinil and were considered by the investigator not or unlikely to be drug related. CONCLUSIONS: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. Clinical benefit was shown at the first assessment and maintained for the 12-week duration of the study. Armodafinil was also associated with significantly reduced interference of ES with daily activities and global fatigue. Armodafinil was well tolerated, with no adverse effect on nighttime sleep or nCPAP use.

Oral appliances for snoring and obstructive sleep apnea: a review.

We conducted an evidence-based review of literature regarding use of oral appliances (OAs) in the treatment of snoring and obstructive sleep apnea syndrome (OSA) from 1995 until the present. Our structured search revealed 141 articles for systematic scrutiny, of which 87 were suitable for inclusion in the evidence base, including 15 Level I to II randomized controlled trials and 5 of these trials with placebo-controlled treatment. The efficacy of OAs was established for controlling OSA in some but not all patients with success (defined as no more than 10 apneas or hypopneas per hour of sleep) achieved in an average of 52% of treated patients. Effects on sleepiness and quality of life were also demonstrated, but improvements in other neurocognitive outcomes were not consistent. The mechanism of OA therapy is related to opening of the upper airway as demonstrated by imaging and physiologic monitoring. Treatment adherence is variable with patients reporting using the appliance a median of 77% of nights at 1 year. Minor adverse effects were frequent whereas major adverse effects were uncommon. Minor tooth movement and small changes in the occlusion developed in some patients after prolonged use, but the long-term dental significance of this is uncertain. In comparison to continuous positive airway pressure (CPAP), OAs are less efficacious in reducing the apnea hypopnea index (AHI), but OAs appear to be used more (at least by self report), and in many studies were preferred over CPAP when the treatments were compared. OAs have also been compared favorably to surgical modification of the upper airway (uvulopalatopharyngoplasty, UPPP). Comparisons between OAs of different designs have produced variable findings. The literature of OA therapy for OSA now provides better evidence for the efficacy of this treatment modality and considerable guidance regarding the frequency of adverse effects and the indications for use in comparison to CPAP and UPPP.

Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study.

STUDY OBJECTIVES: The purpose of this 12-week study was to evaluate the efficacy and safety of adjunct modafinil to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) who experience residual sleepiness despite regular nasal continuous positive airway pressure (nCPAP) use. DESIGN: Twelve-week, open-label trial. SETTING: Twenty-two centers in the United States. PATIENTS: We studied 125 patients with moderate-to-severe OSA (ie, respiratory disturbance index > or =15) before nCPAP therapy and residual daytime sleepiness (Epworth sleepiness scale [ESS] score > or =10) despite effective and regular nCPAP therapy. Patients were studied after completing a 4-week, double-blind, placebo-controlled trial of nCPAP plus modafinil for the treatment of residual daytime sleepiness. INTERVENTIONS AND MEASUREMENTS: Patients received individually titrated doses of modafinil (200 to 400 mg qd). Sleepiness was assessed using the ESS, quality of life was evaluated using the Functional Outcomes of Sleep Questionnaire (FOSQ), and the overall clinical effect was indexed using the clinical global impression of change scale. Adverse events, nCPAP use, and vital sign measurements were also recorded. RESULTS: The significant improvements in daytime wakefulness and sleep-related functional status observed with modafinil treatment during the 4-week, double-blind study were maintained throughout 12 weeks of open-label treatment: week 12 ESS, 7.8 (4.7) vs 14.4 (3.1) at double-blind baseline; week 12 FOSQ, 3.3 (0.6) vs 14.4 (2.7) at double-blind baseline (mean [SD]). The percentage of patients rated as clinically improved increased from 83% after 1 week to > or =93% after 2 to 12 weeks of open-label treatment. Mean (SD) nCPAP use decreased from 6.3 (1.3) h/night at baseline to 5.9 (1.4) h/night (p = 0.004) during open-label treatment. The most common adverse events were headache (28%), anxiety (16%), and nervousness (14%). CONCLUSIONS: Modafinil remained effective and well tolerated as an adjunct therapy for residual daytime sleepiness even after 12 weeks of daily dosing in patients with OSA receiving nCPAP therapy.

Comparison between automatic and fixed positive airway pressure therapy in the home.

We tested the hypothesis that continuous positive airway pressure (CPAP) use and outcomes can be improved by an autotitrating CPAP device in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) who require higher CPAP (10 cm H2O or more). In this multisite randomized single-blind cross-over study, 44 patients (mean age, 49 +/- 10 years) were randomized to 6 weeks at laboratory-determined fixed pressure and 6 weeks on autotitrating CPAP. Average nightly use was greater in automatic mode (306 versus 271 minutes, p = 0.005); median and 95th centile pressures in automatic mode were lower (p < 0.002). Automatic CPAP resulted in better SF-36 Vitality scores (65 +/- 20 versus 58 +/- 23, p < 0.05) and mental health scores (80 +/- 14 versus 75 +/- 18, p < 0.05), but no significant difference in Epworth score (p = 0.065). During automatic therapy, patients reported more restful sleep, better quality sleep, less discomfort from pressure, and less trouble getting to sleep for both the first week of therapy and for the averaged scores for Weeks 2-6 (all p values < 0.006). Patients who require higher fixed CPAP use autotitrating CPAP more and report greater benefit from this therapy.

Recent Developments in Oral Appliance Therapy of Sleep Disordered Breathing.

Oral appliances are increasingly gaining a place in the treatment of sleep disordered breathing caused by upper airway obstruction. This review of publications since 1995 documents substantial progress in the scientific basis for this therapy. Imaging by several techniques has shown that mandibular advancing oral appliances open the airway in awake and anaesthetized subjects, creating the presumption that this effect is maintained in sleep. Three controlled cross-over treatment trials have shown that patients consistently prefer oral appliance over continuous positive airway pressure therapy, especially when the treatment effect is strong. Appliance design and use indicates a preference for adjustable mandibular advancing appliances. Complications of therapy appear to be infrequent, but evidence for safety of long-term use is still limited. Oral appliance therapy can be an effective therapy for sleep disorders caused by upper airway obstruction. Considering the accumulated evidence, it is no longer tenable to label oral appliance therapy an OexperimentalO procedure.