Zolpidem extended-release 12.5 mg associated with improvements in work performance in a 6-month randomized, placebo-controlled trial.

BACKGROUND: Although most research on pharmacotherapy for chronic insomnia focuses on changes in sleep outcomes, the functional impact of treatment is also of great importance to patients, families, physicians, and employers. OBJECTIVE: To analyze changes in functioning at work (or work performance) among a subset of employed subjects (N = 752) from a 24-week, randomized, double-blind, placebo-controlled trial of zolpidem extended-release 12.5 mg taken nightly, at least 3 nights per week, by healthy adults with chronic insomnia. METHODS: Using 2 scales (Time Management and Work Output) from the Work Limitations Questionnaire (WLQ), subjects' health-related work limitations were evaluated at baseline, week 4, week 12, and week 24 (end of study) or premature discontinuation. To compare zolpidem extended-release 12.5 mg with placebo, within-group and between-group differences were analyzed and effect sizes were computed. The relationship of WLQ scores to scores on the Patient Global Impression, Item 1 (PGI-1), scale, the primary outcome measure for benefit to sleep, was also analyzed. Data were obtained from August 31, 2004 through January 6, 2006. RESULTS: Scores on both WLQ scales were substantially elevated at baseline in this population, reflecting impairment relative to healthy controls. The zolpidem extended-release 12.5 mg group had significantly greater improvement at all time points on the WLQ Time Management (P < 0.0001) and Work Output (P < 0.01) scales. Effect size analysis confirmed the clinical relevance of these improvements. Subjects rating their sleep as improved on the PGI-1 had significantly greater improvement on both WLQ scales at week 12 than did those who reported no benefit or worsening (P < 0.01). CONCLUSIONS: Employed adults with chronic insomnia treated with zolpidem extended-release 12.5 mg experienced significantly improved work performance over 24 weeks.

Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study.

STUDY OBJECTIVES: To evaluate long-term efficacy and safety of zolpidem extended-release 3 to 7 nights/week for chronic primary insomnia. DESIGN: Multicenter, 25-week, phase IIIb, randomized, double-blind, placebo-controlled, parallel-group. SETTING: Outpatient; visits every 4 weeks. PATIENTS: Aged 18 to 64 years; DSM-IV criteria for chronic primary insomnia; > or =3 months of difficulty initiating or maintaining sleep or experiencing nonrestorative sleep. INTERVENTIONS: Single-dose zolpidem extended-release 12.5 mg (n = 669) or placebo (n = 349), self-administered from a minimum of 3 nights/week to a maximum of 7 nights/week. MEASUREMENTS AND RESULTS: Patient's Global Impression (PGI) and Clinical Global Impression-Improvement (CGI-I) were assessed every 4 weeks up to week 24. Patient Morning Questionnaire (PMQ), recorded daily, assessed subjective sleep measures-sleep onset latency (SOL), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and quality of sleep (QOS)-and next-day functioning. At week 12, PGI, Item 1 (aid to sleep), the primary endpoint, was scored as favorable (i.e., "helped me sleep") by 89.8% of zolpidem patients vs. 51.4% of placebo patients (P < 0.0001, based on rank score) and at week 24 by 92.3% of zolpidem extended-release patients vs. 59.7% of placebo patients. Zolpidem extended-release also was statistically significantly superior to placebo at every time point for PGI (Items 1-4) and CGI-I (P < 0.0001, rank score), TST, WASO, QOS (P < 0.0001), and SOL (P < or = 0.0014); NAW (Months 2-6; P < 0.0001). Sustained improvement (P < 0.0001, all time points) was observed in morning sleepiness and ability to concentrate (P = 0.0014, month 6) with zolpidem extended-release compared with placebo. Most frequent adverse events for zolpidem extended-release were headache, anxiety and somnolence. No rebound effect was observed during the first 3 nights of discontinuation. CONCLUSIONS: These findings establish the efficacy of 3 to 7 nights per week dosing of zolpidem extended-release 12.5 mg for up to 6 months. Treatment provided sustained and significant improvements in sleep onset and maintenance and also improved next-day concentration and morning sleepiness.

APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia.

INTRODUCTION: Insomnia is a condition affecting 10% to 15% of the adult population and is characterized by difficulty falling asleep, difficulty staying asleep, or nonrestorative sleep, accompanied by daytime impairment or distress. This study evaluates APD125, a selective inverse agonist of the 5-HT(2A) receptor, for treatment of chronic insomnia, with particular emphasis on sleep maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well tolerated. METHODOLOGY: Adult subjects (n=173) with DSM-IV defined primary insomnia were randomized into a multicenter, double-blind, placebo-controlled, 3-way crossover study to compare 2 doses of APD125 (10 mg and 40 mg) with placebo. Each treatment period was 7 days with a 7- to 9-day washout period between treatments. Polysomnographic recordings were performed at the initial 2 screening nights and at nights (N) 1/2 and N 6/7 of each treatment period. RESULTS: APD125 was associated with significant improvements in key sleep maintenance parameters measured by PSG. Wake time after sleep onset decreased (SEM) by 52.5 (3.2) min (10 mg) and 53.5 (3.5) min (40 mg) from baseline to N 1/2 vs. 37.8 (3.4) min for placebo, (P < 0.0001 for both doses vs. placebo), and by 51.7 (3.4) min (P = 0.01) and 48.0 (3.6) min (P = 0.2) at N 6/7 vs. 44.0 (3.8) min for placebo. Significant APD125 effects on wake time during sleep were also seen (P < 0.0001 N 1/2, P < 0.001 N 6/7). The number of arousals and number of awakenings decreased significantly with APD125 treatment compared to placebo. Slow wave sleep showed a statistically significant dose-dependent increase. There was no significant decrease in latency to persistent sleep. No serious adverse events were reported, and no meaningful differences in adverse event profiles were observed between either dose of APD125 and placebo. APD125 was not associated with next-day psychomotor impairment as measured by Digit Span, Digit Symbol Copy, and Digit Symbol Coding Tests. CONCLUSIONS: APD125 produced statistically significant improvements in objective parameters of sleep maintenance and sleep consolidation and was well tolerated in adults with primary chronic insomnia.

Modafinil for excessive sleepiness associated with chronic shift work sleep disorder: effects on patient functioning and health-related quality of life.

OBJECTIVE: We evaluated the effects of modafinil, a wake-promoting agent, on patient functioning, health-related quality of life, and nighttime and daytime sleep in patients with excessive sleepiness associated with shift work sleep disorder (SWSD). METHOD: A 12-week, randomized, double-blind, placebo-controlled study was performed at 31 centers in the United States between February 2001 and March 2002. Adults (N = 278) with excessive sleepiness associated with chronic SWSD (International Classification of Sleep Disorders criteria) were randomly assigned to receive modafinil 200 or 300 mg or placebo, 30 to 60 minutes before each night shift. Effects on patient functioning and quality of life were assessed using the Functional Outcomes of Sleep Questionnaire (FOSQ) and the 36-item Short Form Health Survey (SF-36), respectively. Daily patient diaries were used as a sleep log. RESULTS: Modafinil 300 mg significantly improved mean FOSQ total score relative to placebo (2.3-point increase from baseline vs. 1.6 for placebo; p < .05). Both doses of modafinil significantly improved mean SF-36 mental component scores relative to placebo (mean changes from baseline of 3.2, 3.7, and 0.7 points in the modafinil 300-mg, modafinil 200-mg, and placebo groups, respectively; p < .05 for each comparison vs. placebo). Modafinil did not adversely affect sleep when sleep was desired or caffeine use. Modafinil was well tolerated. Headache (21.5%) and nausea (12.4%) were the most common adverse events in modafinil-treated patients. Differences between modafinil and placebo for vital sign measurements, physical examination findings, or electrocardiography results were not clinically meaningful. CONCLUSIONS: Modafinil significantly improves functioning and quality of life in patients with SWSD. Modafinil is an effective treatment for excessive sleepiness associated with SWSD.

Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in patients with narcolepsy participating in two clinical trials of sodium oxybate.

BACKGROUND: In evaluating pathologic sleepiness, the Epworth Sleepiness Scale (ESS) assesses subjective sleep propensity; the Maintenance of Wakefulness Test (MWT) is an objective measure of the ability to stay awake. This analysis evaluated the strength of the correlation between ESS and MWT with regard to absolute values in scores. METHODS: Data were analyzed separately from the intent-to-treat populations of two eight-week clinical trials of sodium oxybate for the treatment of narcolepsy, SXB-15 and SXB-22. For all treatment groups, correlations between ESS and MWT were evaluated at baseline, week four, and week eight using the Pearson product-moment correlation coefficient. RESULTS: Overall, correlations across all treatment groups in each study described an inverse relationship, reflecting the scoring of each measure (ie, whereas higher ESS scores indicate greater sleepiness, higher MWT scores indicate a greater ability to remain awake). Significant correlations of low-to-moderate strength were observed at all time points in both studies. In SXB-15, correlation coefficients were -0.272, -0.365, and -0.343 at baseline (n = 221), week four (n = 212), and week eight (n = 205), respectively, with all P < 0.0001. Similarly, in SXB-22, correlation coefficients were -0.302 (n = 216), -0.418 (n = 211), and -0.432 (n = 196) at the three time points, respectively, also with all P < 0.0001. CONCLUSION: Although all correlations showed statistical significance, they were of low-to-moderate strength. These results indicate that ESS and MWT measure features of pathologic sleepiness that may be distinct, but partially overlapping. These data corroborate those of other studies, suggesting that physiologic mechanisms that regulate alertness and sleep propensity may function somewhat independently.

Laboratory and field studies of naps and caffeine as practical countermeasures for sleep-wake problems associated with night work.

STUDY OBJECTIVES: To evaluate the effects of napping, caffeine, and napping plus caffeine on performance and alertness in both laboratory and field settings. DESIGN: (1) Laboratory Study: parallel-groups design with random assignment to 1 of 4 experimental conditions. (2) Field Study: crossover design. SETTING: Sleep laboratory and field settings. PARTICIPANTS: (1) Laboratory Study: 68 healthy individuals; (2) Field Study: 53 shiftworkers who worked nights or rotating shifts. INTERVENTIONS: (1) Laboratory Study: an evening nap opportunity before the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4 nights, caffeine taken nightly, the combination of the nap and caffeine conditions, or placebo. (2) Field Study: an evening nap on the first 2 of 4 consecutive night shifts plus caffeine taken nightly versus placebo taken nightly without naps. MEASUREMENTS AND RESULTS: (1) Laboratory Study: Napping, caffeine, and their combination all improved alertness and performance as measured by Maintenance of Wakefulness Test and Psychomotor Vigilance Task, but the combination of napping and caffeine was best in improving alertness. (2) Field Study: Napping plus caffeine improved performance as measured by Psychomotor Vigilance Test and decreased subjective sleepiness in individuals working the night shift. CONCLUSIONS: Napping plus caffeine helps improve performance and alertness of night-shift workers.

An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia.

BACKGROUND AND PURPOSE: To evaluate the efficacy, safety, and dose response of Ramelteon, a novel highly selective MT1/MT2 receptor agonist, in patients with chronic primary insomnia. PATIENTS AND METHODS: A randomized, multicenter, double-blind, placebo-controlled, five-period crossover study design was performed. A total of 107 patients, aged 18-64 years, were randomized into a dosing sequence that included 4, 8, 16, and 32 mg of Ramelteon and placebo. Patients received all five treatments, with a 5- to 12-day washout period between treatments, and served as their own controls. Medication was administered 30 min before habitual bedtime and polysomnographic monitoring. Next-day residual effects were assessed with two visual analog scales (mood and feeling), digit symbol substitution test (DSST), word-list memory tests (immediate recall and delayed recall), and a post-sleep questionnaire that ascertained patients' alertness and ability to concentrate. RESULTS: All tested doses of Ramelteon resulted in statistically significant reductions in latency to persistent sleep (LPS) and increases in total sleep time (TST). No next-day residual effects were apparent at any dose, as compared with placebo. There were no differences in the number or type of adverse events between any active treatment and placebo group. The most commonly reported adverse events were headache, somnolence, and sore throat. CONCLUSIONS: Ramelteon demonstrated a statistically significant reduction in LPS and a statistically significant increase in TST, with no apparent next-day residual effects, in patients with chronic primary insomnia.

A polysomnography study of eszopiclone in elderly patients with insomnia.

OBJECTIVE: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia. METHODS: This was a randomized, double-blind, placebo-controlled 2-week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] >or= 20 min and latency to persistent sleep >or= 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1-14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis. RESULTS: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo (p < 0.05 for all) with a trend in patient-reported morning sleepiness (p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps (p = 0.03) and less cumulative naptime (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively). CONCLUSION: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.

Selected sleep disorders: restless legs syndrome and periodic limb movement disorder, sleep apnea syndrome, and narcolepsy.

Sleep disorders, including restless legs syndrome and periodic limb movement disorder, sleep apnea syndrome, and narcolepsy, are prevalent medical conditions, likely to be seen by practicing psychiatrists. Awareness of these conditions and their presentations, pathophysiology, and treatment allows psychiatrists to treat these conditions where appropriate, to minimize complications and health consequences associated with delayed diagnosis, and to reduce the burden of disease that these conditions may place on patients already experiencing primary psychiatric disorders.

A 2-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia.

STUDY OBJECTIVES: Evaluate the efficacy of eszopiclone in primary insomnia. DESIGN/SETTING: Randomized, double-blind, placebo-controlled multicenter in outpatient setting with weekly visits. PARTICIPANTS: Two-hundred thirty one men and women aged 65 to 85 years (mean age 72.3 years) with primary insomnia, as defined by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. INTERVENTIONS: Eszopiclone 1 mg (n = 72), eszopiclone 2 mg (n = 79), or placebo (n = 80) nightly for 2 weeks. MEASUREMENTS/RESULTS: Efficacy was assessed using an interactive voice response system. Following the predefined hierarchical testing strategy, the eszopiclone 2-mg group had a significantly shorter sleep latency compared with placebo over the double-blind period (P = .0034). The eszopiclone 2-mg group had significantly longer total sleep time (P = .0003) and eszopiclone 1-mg group had significantly shorter sleep latency (P < or = .012) compared with placebo. The eszopiclone 1-mg group was not significantly different from placebo on total sleep time or any other secondary efficacy endpoint. Secondary analyses indicated that the eszopiclone 2-mg group had significantly less wake after sleep onset; significantly fewer and shorter in duration daytime naps; and significantly higher ratings of sleep quality and depth, daytime alertness, and sense of physical well-being compared with placebo (P < .05). Eszopiclone was well tolerated. The most frequent treatment-related adverse event was unpleasant taste. CONCLUSION: Nightly treatment with eszopiclone 1 mg effectively induced sleep, while the 2-mg dose was effective in inducing and maintaining sleep. Eszopiclone was well tolerated in elderly patients with primary insomnia, and the sleep efficacy was accompanied by significantly less napping and significantly higher ratings of daytime alertness, sense of physical well-being, and several quality-of-life parameters at the higher dose.

Therapeutic options in the treatment of insomnia.

Pharmacologic and nonpharmacologic therapies both have roles in the treatment of insomnia. The benzodiazepines, when first introduced, were a major improvement over earlier treatments for insomnia in terms of their safety and efficacy. Since then, the nonbenzodiazepine benzodiazepine receptor agonists have been developed, which have provided advantages over the older medications and are currently first-line medication treatment for insomnia. Although antidepressants, antipsychotics, and anticonvulsants are often prescribed for the treatment of insomnia, they are not approved by the U.S. Food and Drug Administration for this indication and have side effects that are sometimes severe. New types of medications that have different modes of action from the benzodiazepine receptor agonists are now being developed, and one, a selective melatonin receptor agonist, has recently been approved for treatment of insomnia. Nonpharmacologic therapies can also help patients learn how to fall asleep faster and improve sleep quality. It is important for physicians to teach patients good sleep hygiene as part of their treatment. Cognitive-behavioral therapy is effective in the treatment of insomnia, alone and in combination with pharmacotherapy, but finding a qualified provider can be difficult and the patient must be willing to take the time to learn the therapies and wait for them to show effect.

Effects of temazepam 7.5 mg and temazepam 15 mg on sleep maintenance and sleep architecture in a model of transient insomnia.

OBJECTIVE: To compare the effects of temazepam 7.5 mg and temazepam 15 mg on sleep maintenance during the last third of the night (last 160 min) and on sleep architecture throughout the night. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of a previously reported double-blind, randomized, uncontrolled, parallel-group, multicenter study. Healthy subjects with previous but no current complaints of transient insomnia were enrolled. Transient insomnia was induced in the sleep laboratory by means of the 'first night' effect and by implementing a 2-h phase advance. The effects of both doses of temazepam on polysomnographic measures of sleep were evaluated for 1 night. The primary, prospectively-defined analysis of this study showed that 7.5-mg and 15-mg doses of temazepam had equivalent effects on latency to persistent sleep, total sleep time, and the number of sleep interruptions recorded over an 8-h period. Both doses were well tolerated. The post hoc analysis reported here compared these 2 doses for their effects on sleep maintenance and architecture. Sleep efficiency during the last third of the night was designated as the primary endpoint. The methodology for this analysis was fully defined and documented prior to re-analysis of the database for these parameters. RESULTS: Sixty-five subjects received temazepam 7.5 mg and 66 received temazepam 15 mg. No statistically significant differences between doses were detected for sleep efficiency or number of sleep interruptions during the last third of the night. Sleep architecture (measured over 8 h) did not differ significantly between groups. CONCLUSIONS: The 7.5-mg and 15-mg doses of temazepam were equally effective for maintaining sleep during the last third of the night. Continuity of sleep throughout the night, as reflected by sleep architecture, was also similar regardless of dose. In keeping with current practice guidelines, initiation of treatment with temazepam for transient insomnia should begin with the 7.5 mg dose.

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 of temazepam 7.5 mg with temazepam 15 mg for the treatment of transient insomnia.

OBJECTIVE: To demonstrate the equivalent efficacy of temazepam 7.5 mg and temazepam 15 mg for the treatment of transient insomnia. RESEARCH DESIGN AND METHODS: This was a double-blind, parallel group, multicenter study. Healthy male and female subjects with previous but not current complaints of transient insomnia were enrolled. Transient insomnia was induced in the sleep laboratory by means of the 'first night' effect and by implementing a 2-h phase advance. The effects of both doses of temazepam on polysomnographic (PSG) measures of sleep were evaluated for one night. Latency to persistent sleep (LPS) and total sleep time (TST) were designated as the primary efficacy endpoints. RESULTS: One hundred and thirty-one subjects completed the study: 65 received the 7.5-mg dose, and 66 received the 15-mg dose. Treatment groups begin with the lowest effective dose, i.e., 7.5 mg. were well matched based on background demographics. No statistically significant differences between doses were detected for LPS, TST,or any other objective (PSG) measure of sleep. Furthermore, both doses were found to be clinically equivalent for LPS and TST based on predetermined criteria. Temazepam was well tolerated, and no significant differences between doses were found for adverse event (AE) incidence, mean score on the Digit Symbol Substitution Task, or mean scores on questions related to tolerability from the Leeds Sleep Evaluation Questionnaire. CONCLUSIONS: The 7.5-mg and 15-mg doses of temazepam were equally effective for the treatment of transient insomnia. In keeping with current practice guidelines, initiation of treatment with temazepam for transient insomnia should

Comparative efficacy of zolpidem and temazepam in transient insomnia.

This study compared hypnotic effects of zolpidem 10 mg, temazepam 15 mg and placebo in healthy adults. Two factors expected to promote insomnia, the 'first night effect' and a 2-hour phase advance, were combined in a single night laboratory-based double-blinded protocol. This was a multi-center study, with data collected in 13 sleep laboratories. Subjects with normal sleep histories and without prior sleep laboratory experience were randomly assigned to treatment groups. Medications were administered 15 min before lights out, with polysomnographic monitoring for 7.5 h. Subjective questionnaires and performance tests, digit symbol substitution test (DSST) and symbol copying test (SCT), were administered at study entry and after arising. 630 subjects completed the study and provided data analyzed using repeated measures ANOVAs. Neither agent significantly reduced objective sleep latency relative to placebo. Zolpidem reduced awakenings and wake after sleep onset (WASO); temazepam did not. Both agents improved sleep efficiency and most subjective sleep measures relative to placebo, with zolpidem superior for five of six subjective outcome measures compared to temazepam. SCT, morning sleepiness and morning concentration were not altered by any treatment. Zolpidem significantly reduced morning DSST performance; temazepam did not. Zolpidem 10 mg provided greater subjective hypnotic efficacy than temazepam 15 mg in this model of transient insomnia, with reduced polysomnographic awakenings and WASO. Impairment of DSST was seen with zolpidem but not temazepam. Copyright 2001 John Wiley & Sons, Ltd.

The effect of armodafinil on patient-reported functioning and quality of life in patients with excessive sleepiness associated with shift work disorder: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To examine whether treatment with armodafinil for 6 weeks affected patient-reported overall functioning and daily quality of life compared with placebo in patients with excessive sleepiness associated with shift work disorder. METHOD: This 6-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 45 sleep centers across the United States between February and October 2010. Patients included in the study were 18 to 65 years of age and diagnosed with excessive sleepiness associated with shift work disorder on the basis of the International Classification of Sleep Disorders: Diagnostic and Coding Manual, Second Edition and DSM-IV-TR criteria. These patients also experienced late-in-shift sleepiness between 4 AM and 8 AM (Karolinska Sleepiness Scale score ≥ 6) and were functionally impaired (Global Assessment of Functioning score < 70). Patients were administered 150 mg of armodafinil or placebo on nights worked, and efficacy measures included changes in patient-reported overall functioning (modified Sheehan Disability Scale [SDS-M]) and daily quality of life (10-question Functional Outcomes of Sleep Questionnaire [FOSQ-10]). RESULTS: Patients treated with armodafinil had significantly greater improvement in SDS-M composite scores at final visit (last observation carried forward) (-6.8 vs -4.5, respectively, P = .0027) than those receiving placebo. Although the armodafinil group, compared to the placebo group, showed a greater improvement in total FOSQ-10 score from baseline to final visit (+3.4 vs +2.7, respectively, P = .0775), a statistically significant improvement was observed only at week 6 (+3.6 vs +2.7, respectively, P = .0351). CONCLUSIONS: These findings are consistent with our previous report on clinician-rated measures of efficacy by demonstrating that armodafinil improves patient-rated functioning in patients with shift work disorder. Additionally, the current findings show for the first time that armodafinil may have benefits on quality of life after 6 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01080807.

Efficacy and tolerability of armodafinil: effect on clinical condition late in the shift and overall functioning of patients with excessive sleepiness associated with shift work disorder.

OBJECTIVE: This study examined the effect of armodafinil on late-in-shift clinical condition, wakefulness, and overall functioning of patients with shift work disorder. METHODS: Patients with clinically diagnosed shift work disorder received armodafinil or placebo on nights worked for 6 weeks. Patients included in the study experienced late-in-shift sleepiness between 4 AM and 8 AM (Karolinska Sleepiness Scale ≥6) and were functionally impaired (Global Assessment of Functioning <70). Efficacy was determined by improvements in clinical condition (Clinical Global Impression-Change), late-in-the-shift Karolinska Sleepiness Scale score, and overall Global Assessment of Functioning score. Tolerability was assessed. RESULTS: Patients receiving armodafinil showed significant improvements in late-in-shift clinical condition, wakefulness, and global functioning, compared to placebo at final visit. Armodafinil was generally well tolerated. CONCLUSIONS: Armodafinil improved clinical condition and wakefulness late in the night shift of patients with shift work disorder. Overall patient functioning was also improved.

An introduction to the clinical correlates of disrupted slow-wave sleep.

Chronic sleep deficits have been shown to lead to problems with cognition and memory, and evidence supports an association between deficits in slow-wave sleep and a variety of clinical and psychiatric disorders. Improving sleep architecture through an increase in slow-wave sleep, with or without increases in total time asleep, may lead to improvements in these associated disorders. Further research and the development of novel sleep therapies, both pharmacologic and nonpharmacologic, are needed.