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Biomedical subjects

James K Walsh

Publications and source records attributed to James K Walsh.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in adults with primary insomnia.

BACKGROUND AND PURPOSE: To evaluate the clinical efficacy and safety of modified-release zolpidem (zolpidem-MR 12.5mg) for the treatment of primary insomnia in adults. PATIENTS AND METHODS: Two hundred and twelve (123 women, 89 men; mean age 44.3+/-SD 3.0 years), Diagnostic and Statistical Manual of Mental Disorders--4th Edition (DSM-IV)-defined primary insomnia patients were randomized in a double-blind, placebo-controlled, parallel-group study. The study was completed by 192 patients. Patients received 3 weeks of nightly treatment with either zolpidem-MR 12.5mg or placebo, preceded and followed by two nights of single-blind placebo. The main outcome measures were mean polysomnographic (PSG) sleep parameters of nights 1/2 and nights 15/16 of double-blind treatment and daily subjective sleep estimates from sleep questionnaires to assess efficacy, and PSG parameters of nights 22 and 23 of single-blind placebo substitution to assess the effect of drug discontinuation. RESULTS: Relative to placebo, zolpidem-MR 12.5mg improved sleep maintenance by significantly reducing PSG wake time after sleep onset (WASO) during the first 6h of sleep as well as the number of awakenings. Consistent with the effects of standard zolpidem, zolpidem-MR also significantly reduced latency to persistent sleep, and significantly increased sleep efficiency, both at the beginning and after 2 weeks of double-blind treatment. There was no evidence of next-day residual effects as measured objectively by psychometric tests. Rebound insomnia on the first night after abrupt discontinuation resolved the following night. Overall, zolpidem-MR was well tolerated. CONCLUSIONS: Zolpidem-MR 12.5mg is effective and safe in treating primary insomnia in adults and improves sleep maintenance, induction and duration of sleep.

Adolescent↗
PubMed2006

Pharmacologic management of insomnia: past, present, and future.

Views on the etiology and morbidities associated with insomnia are evolving and affect clinicians' approach to the pharmacologic management of insomnia. Currently, benzodiazepine receptor agonists (BzRAs) and a single melatonin receptor agonist are recognized as safe and efficacious hypnotics. Variability in BzRAs, pharmacokinetics, and manipulation of dose provide clinicians with options that meet the needs of most patients. Other drugs (eg, sedating antidepressants) also are used commonly in clinical practice to treat insomnia, but evidence is lacking to support this most cases. Improvement in managing insomnia will result from systematic research with these drugs, with drugs in development, and with novel uses, such as co-therapy.

Drug Therapy↗
PubMed2006

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.

Adolescent↗
PubMed2006

The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy.

OBJECTIVE: This study assessed the efficacy and safety of armodafinil, the longer half-life enantiomer of modafinil, for the treatment of excessive sleepiness in patients with narcolepsy. RESEARCH DESIGN AND METHODS: This was a multicenter double-blind study with 196 patients (aged 18-65 years) randomized to receive armodafinil 150 mg (n = 65), armodafinil 250 mg (n = 67), or placebo (n = 64) once daily for 12 weeks. MAIN OUTCOME MEASURES: Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) (six 20-min subtests across the day), the Clinical Global Impression of Change (CGI-C), subjective measures of sleepiness (Epworth Sleepiness Scale), patient diaries, and evaluations of cognitive performance (Cognitive Drug Research) and fatigue (Brief Fatigue Inventory). RESULTS: Armodafinil significantly increased MWT mean sleep latency (at 0900-1500) compared with placebo. The mean change from baseline at final visit for armodafinil was an increase of 1.3, 2.6, and 1.9 min in the 150-mg, 250-mg, and combined groups, respectively, compared with a decrease of 1.9 min for placebo (p < 0.01 for all three comparisons). Mean late-day MWT latency (1500-1900) was also significantly improved (difference of armodafinil combined group relative to placebo at final visit: 2.8 min, p = 0.0358). The proportions of patients who showed at least minimal improvement in the CGIC rating from baseline to final visit in the armodafinil 150-mg, 250-mg, and combined groups were 69%, 73%, and 71%, respectively, compared with 33% for placebo (p < 0.0001). Both doses were associated with statistically significant improvements in memory, attention, and fatigue (p < 0.05). The most common adverse events in patients receiving armodafinil were headache, nausea, and dizziness. CONCLUSIONS: Armodafinil significantly improved ability to sustain wakefulness throughout the day in patients with narcolepsy. Armodafinil also significantly improved overall clinical condition, memory, attention, and fatigue when compared with placebo.

Adolescent↗
PubMed2006

Tiagabine is associated with sustained attention during sleep restriction: evidence for the value of slow-wave sleep enhancement?

STUDY OBJECTIVES: To evaluate the impact of enhanced slow-wave sleep (SWS) on behavioral, psychological, and physiologic changes resulting from sleep restriction DESIGN: A double-blind, parallel-group, placebo-controlled design was used to compare tiagabine, 8 mg, (a SWS-enhancing drug) to placebo during 4 nights of sleep restriction (time in bed = 5 hours per night). Behavioral, psychological, and physiologic measures of the impact of sleep restriction were compared between groups at baseline, during sleep restriction, and following recovery sleep. SETTING: Two sleep research laboratories. PARTICIPANTS: Thirty-eight healthy adults; 9 men and 10 women (mean age: 26.0 +/- 6.1 years) in the placebo group and 8 men and 11 women (mean age: 26.7 +/- 8.1 years) in the tiagabine 8 mg group INTERVENTIONS: Both experimental groups underwent 4 nights of sleep restriction. Each group received either tiagabine 8 mg or placebo on all sleep-restriction nights, and both groups received placebo on baseline and recovery nights. MEASUREMENTS AND RESULTS: Polysomnography documented a SWS-enhancing effect of tiagabine. The placebo group displayed the predicted deficits due to sleep restriction on the Psychomotor Vigilance Task and the Multiple Sleep Latency Test. Compared with placebo, the tiagabine group did not demonstrate impairment in sustained attention on the Psychomotor Vigilance Test, performed better on the Wisconsin Card Sorting Task, reported more restorative sleep, and had less of an increase in afternoon-evening salivary free cortisol. Multiple Sleep Latency Test, ratings of sleepiness, recovery sleep, and other measures did not differ between groups. CONCLUSIONS: To our knowledge these findings are the first to be consistent with the hypothesis that pharmacologic SWS enhancement reduces selective aspects of the behavioral, psychological, and physiologic impact of sleep restriction.

Adult↗
PubMed2005

Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia.

BACKGROUND AND PURPOSE: To evaluate the effect of tiagabine on sleep and next-morning alertness and performance in adult patients with primary insomnia. PATIENTS AND METHODS: Patients with primary insomnia, as defined by Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV), received tiagabine 4, 8, 12, 16 mg, and placebo in a randomized, double-blind, five-period, Latin square, crossover study. Efficacy was assessed using polysomnographic and self-report techniques; residual effects were evaluated using the Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: Fifty-eight patients (40f, 18m; mean age 46.6+/-8.0 years) were randomized. Results showed a significant dose-dependent increase in slow wave sleep percentage with all tiagabine doses, a trend toward a dose-dependent increase in total sleep time, and no effect on latency to persistent sleep. Wake after sleep onset also decreased in a dose-dependent manner, with the 16-mg dose differing significantly from placebo. The tolerability profiles of tiagabine 4 and 8 mg were similar to placebo. The most common adverse events reported following tiagabine 12 and 16 mg were dizziness and nausea. Residual effects were only apparent at 12- and 16-mg doses. CONCLUSIONS: Tiagabine increased slow wave sleep and reduced wake after sleep onset in a dose-dependent manner. Tiagabine dosages up to 8 mg did not compromise next-morning alertness and psychomotor performance in adult patients with primary insomnia. Further investigation of tiagabine doses up to 8 mg is warranted.

Adult↗
PubMed2005

An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia.

BACKGROUND AND PURPOSE: A double-blind placebo-controlled study of eszopiclone found significant, sustained improvement in sleep and daytime function. The 6-month open-label extension phase is described herein. PATIENTS AND METHODS: Adults (21-64) with primary insomnia who reported sleep duration <6.5 h/night or sleep latency >30 min/night were included. Patient-reported endpoints included sleep and daytime function. Safety and compliance were assessed at monthly clinic visits. The final double-blind month was used as the baseline for efficacy analyses of the open-label period. RESULTS: Patients who were initially randomized to double-blind placebo and then switched to open-label eszopiclone (n=111) significantly reported the following: (1) decreased sleep latency, wake time after sleep onset, and number of awakenings; (2) increased total sleep time and sleep quality; and (3) improved ratings of daytime ability to function, alertness and sense of physical well-being compared to baseline (P 5% of patients. CONCLUSIONS: The significant improvements in sleep and daytime function were evident in those switched from double-blind placebo to 6 months of open-label eszopiclone therapy and were sustained during the 6 months of open-label treatment for those receiving prior double-blind eszopiclone. During 12 months of nightly treatment, eszopiclone 3mg was well tolerated; tolerance was not observed.

Adult↗
PubMed2005

Modafinil for excessive sleepiness associated with shift-work sleep disorder.

BACKGROUND: Patients with shift-work sleep disorder chronically have excessive sleepiness during night work and insomnia when attempting to sleep during the day. We evaluated the use of modafinil for treating sleepiness in patients with this disorder. METHODS: In a three-month, double-blind trial, we randomly assigned 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift. Assessments were performed with the use of the nighttime Multiple Sleep Latency Test, the Clinical Global Impression of Change, the Psychomotor Vigilance Test, diaries of patients, and daytime polysomnography. After randomization, we conducted monthly assessments. RESULTS: Treatment with modafinil, as compared with placebo, resulted in a modest improvement from baseline in mean (+/-SEM) nighttime sleep latency (the interval between the time a person attempts to fall asleep and the onset of sleep) (1.7+/-0.4 vs. 0.3+/-0.3 minutes, respectively; P=0.002), and more patients had improvement in their clinical symptoms (74 percent vs. 36 percent, respectively; P<0.001). Patients who were receiving modafinil also had a reduction in the frequency and duration of lapses of attention during nighttime testing of their performance on the Psychomotor Vigilance Test (change from baseline, a reduction in lapse frequency of 2.6 vs. an increase of 3.8, respectively; P<0.001), and proportionally fewer patients reported having had accidents or near accidents while commuting home (29 percent vs. 54 percent, respectively; P<0.001). Despite these benefits, patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. Modafinil did not adversely affect daytime sleep as compared with placebo. Headache was the most common adverse event. CONCLUSIONS: Treatment with 200 mg of modafinil reduced the extreme sleepiness that we observed in patients with shift-work sleep disorder and resulted in a small but significant improvement in performance as compared with placebo. However, the residual sleepiness that was observed in the treated patients underscores the need for the development of interventions that are even more effective.

Adult↗
PubMed2005

Dose-response effects of tiagabine on the sleep of older adults.

STUDY OBJECTIVES: To evaluate the dose- response effects of tiagabine on sleep and safety measures in healthy older adults. DESIGN: Randomized, double-blind, Latin-square design. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-four healthy older adults (11 men, 13 women; mean age 68.0 +/- 6.2 years) INTERVENTIONS: Tiagabine 2, 4, or 8 mg, or placebo, each given on two consecutive nights. MEASUREMENTS AND RESULTS: Polysomnography revealed that compared with placebo, tiagabine 4 mg increased total sleep time, reduced wake after sleep onset, and increased minutes of slow-wave sleep. Tiagabine 8 mg decreased wake after sleep onset, increased slow-wave sleep, and improved a sleep-continuity index. No differences were seen between the 2-mg dose and placebo. Subjective ratings indicated fewer awakenings with the 8-mg dose. Central nervous system adverse events were somewhat higher in the 8-mg condition only. Measures of morning performance were minimally affected. CONCLUSIONS: Research with tiagabine at dosages of 8 mg or less appears warranted in elderly clinical populations.

Aged↗
PubMed2005

Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment.

OBJECTIVE: Evaluate the efficacy of ramelteon, an MT/1MT2-receptor agonist, for the treatment of transient insomnia in healthy adults. DESIGN: Randomized, double-blind, placebo-controlled design using a model of transient insomnia related to sleeping in a novel environment. SETTING: Fourteen sleep research centers. PARTICIPANTS: Healthy adults (N=375; 228 women), aged 35 to 60 years, who had never previously slept in a sleep laboratory and had a reported usual sleep duration of 6.5 to 8.5 hours and usual bedtime between 8:30 PM and midnight. INTERVENTIONS: Single administration of ramelteon (16 or 64 mg) or placebo 30 minutes before bedtime. OUTCOME MEASURES: Primary efficacy measure was latency to persistent sleep. Also evaluated were total sleep time, wake after sleep onset, percentage of each sleep stage, subjective estimates of sleep from postsleep questionnaire, number of awakenings, and subjective number of awakenings. Residual effects were assessed via Digit Symbol Substitution Test and postsleep questionnaire. RESULTS: Participants in ramelteon-treated groups had significantly shorter latency to persistent sleep relative to placebo. They also were associated with significantly longer total sleep time. Wake after sleep onset and time spent in each sleep stage were not significantly different from placebo. The use of ramelteon (16 mg) was associated with a shorter subjective sleep latency compared to placebo. Other subjective measures of sleep did not differ significantly from placebo. Digit Symbol Substitution Test scores did not differ significantly among the 3 groups, but the use of the 64-mg [corrected] dose was associated with subjective reports of impairment in the morning. CONCLUSIONS: Ramelteon significantly improved latency to persistent sleep and total sleep time in this model of transient insomnia in healthy adults. No dose-related differences in latency to persistent sleep were observed, and both doses were well tolerated.

Adult↗
PubMed2004

Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers.

STUDY OBJECTIVES: Although there are considerable data demonstrating the impact of shift work on sleep and alertness, little research has examined the prevalence and consequences of shift work sleep disorder in comparison to the difficulties with insomnia and excessive sleepiness experienced by day workers. The present study was designed to determine the relative prevalence and negative consequences associated with shift work sleep disorder in a representative sample drawn from the working population of metropolitan Detroit. DESIGN: Random-digit dialing techniques were used to assess individuals regarding their current work schedules and a variety of sleep- and non-sleep-related outcomes. SETTING: Detroit tricounty population. PARTICIPANTS: A total of 2,570 individuals aged 18 to 65 years from a representative community-based sample including 360 people working rotating shifts, 174 people working nights, and 2036 working days. MEASUREMENTS AND RESULTS: Using standardized techniques, individuals were assessed for the presence of insomnia and excessive sleepiness, based on DSM-IV and ICSD criteria. Those individuals with either insomnia or excessive sleepiness and who were currently working rotating or night schedules were classified as having shift work sleep disorder. Occupational, behavioral, and health-related outcomes were also measured. Individuals who met criteria for shift work sleep disorder had significantly higher rates of ulcers (odds ratio = 4.18, 95% confidence interval = 2.00-8.72), sleepiness-related accidents, absenteeism, depression, and missed family and social activities more frequently compared to those shift workers who did not meet criteria (P < .05). Importantly, in most cases, the morbidity associated with shift work sleep disorder was significantly greater than that experienced by day workers with identical symptoms. CONCLUSION: These findings suggest that individuals with shift work sleep disorder are at risk for significant behavioral and health-related morbidity associated with their sleep-wake symptomatology. Further, it suggests that the prevalence of shift work sleep disorder is approximately 10% of the night and rotating shift work population.

Adolescent↗
PubMed2004

Modafinil improves alertness, vigilance, and executive function during simulated night shifts.

STUDY OBJECTIVES: To assess the effect of 200 mg of modafinil compared to placebo on alertness, neurobehavioral performance, and executive function during 4 consecutive simulated night shifts. DESIGN: Double-blind, randomized, parallel groups. SETTING: Sleep research facility. PARTICIPANTS: 32 male and female volunteers between the ages of 18 and 55 years. INTERVENTIONS: 200 mg of modafinil or placebo given nightly on the 4 consecutive simulated night shifts. MEASUREMENTS AND RESULTS: Subjects were randomly assigned to 1 of the 2 treatment conditions, following medical, psychiatric, and polysomnographic screening. On 4 consecutive nights, subjects took study drug at 2200, and then from about 2300 to 0730 participated in a simulated night shift that included the Maintenance of Wakefulness Test, Psychomotor Vigilance Test, Digit Symbol Substitution Test, measures of subjective alertness, and multiple executive-function measures. At 0800, daytime sleep periods were recorded polysomnographically for 6 to 8 hours. Alertness--as measured by the MWT, vigilance and reaction time as indexed by Psychomotor Vigilance Test lapses, and slowest 10% of reaction times--and 3 executive-function tasks showed significant enhancement with modafinil versus placebo. Subjective sleepiness at night and some performance measures did not show consistent treatment differences. Daytime sleep showed minimal differences between conditions. CONCLUSIONS: The physiologic sleepiness and neurobehavioral deficits that occurred during the hours of a typical night shift were clearly attenuated by modafinil. Modafinil also had beneficial effects on some measures of executive function.

Adolescent↗
PubMed2004

The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium.

This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.

Antidepressive Agents, Second-Generation↗
PubMed2004

Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia.

INTRODUCTION: While it is common practice that hypnotics are used on a non-nightly basis, few investigations have been undertaken to evaluate the efficacy of the intermittent dosing strategy. The present study was designed to further evaluate this issue within a large scale, double-blind, placebo-controlled, long-term trial. METHOD: Patients who met DSM-IV criteria for primary insomnia participated in the study from January 2000 through October 2001. Patients were randomly assigned to 1 of 2 treatment groups (zolpidem 10 mg or placebo) for a period of 12 weeks. Ten pills were provided in foil packs on an every-other-week basis, and patients were instructed to take no fewer than 3 and no more than 5 pills per week. Sleep was evaluated daily with sleep diaries. Pill use was recorded in the sleep diaries. RESULTS: 199 patients (mean +/- SD age = 41.0 +/- 12.8 years; 71% female) were randomly assigned to treatment. On mean, patients receiving zolpidem exhibited (vs. baseline) a 42% decrease in sleep latency, a 52% reduction in number of awakenings, a 55% decrease in wake time after sleep onset, and a 27% increase in total sleep time. These positive clinical gains did not diminish with time and were not associated with dose escalation. There was also no evidence of rebound insomnia. CONCLUSIONS: Over a period of 12 weeks of intermittent treatment with zolpidem, sleep continuity was significantly improved, the clinical gains were sustained, and there was no evidence of subjective rebound insomnia between doses or increases in the amount of medication used during the study interval.

Adolescent↗
PubMed2004

Clinical and socioeconomic correlates of insomnia.

Insomnia is characterized by difficulty falling asleep (sleep onset disturbance), difficulty staying asleep (sleep maintenance disturbance), or poor quality (nonrestorative) sleep, leading to impairment of next-day functioning, including psychological distress. Published prevalence estimates of insomnia vary considerably, very likely due to differences in definitions, study setting, and data collection methods. However, estimates based on large population-based surveys provide a rather constant prevalence rate for chronic insomnia in the United States of about 10% (approximately 25 million people). Chronic insomnia is associated with numerous physical and psychiatric conditions and is more common in women and the elderly. Although it is often perceived as a symptom of depression, insomnia is also a precursor of depression and is associated with a substantial increase in the relative risk of major depression. Chronic insomnia is correlated with impaired mood, subjective functioning, and quality of life and, in some cases, with increased daytime sleepiness and accident risk. Those reporting insomnia have higher rates of absenteeism and health care utilization. Direct costs of insomnia have been estimated to be $13.9 billion annually, with a large majority of costs attributable to nursing home care. Chronic insomnia is a common problem, often associated with negative waking mood or function. As such, heightened clinical attention and clinical research appear warranted.

Adolescent↗