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Timothy Roehrs

Publications and source records attributed to Timothy Roehrs.

11 recordsLinked to original sources

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↗

Ethanol and sleep loss: a "dose" comparison of impairing effects.

STUDY OBJECTIVES: Studies to assess the risks associated with sleep loss relative to the well-documented risks of alcohol are limited in number and design. This study compared the "dose"-related sedative, performance-impairing, and amnestic effects of sleep loss to those of ethanol ingestion. DESIGN: Mixed-design experiment with random assignment to a sleep loss (n=12) or ethanol (n=20) group, with each participant assessed under 4 conditions. PARTICIPANTS: Thirty-two healthy normal adult volunteers, aged 21 to 35 years. INTERVENTIONS: In sleep loss, participants had 8, 6, 4, and 0 hours time in bed, producing 0, 2, 4, and 8 hours of sleep loss. For ethanol, participants ingested 0.0 g/kg, 0.3 g/kg, 0.6 g/kg, and 0.9 g/kg ethanol from 8:30 AM to 9:00 AM after 8 hours of time in bed the previous night. Each participant received his or her 4 doses of ethanol or sleep loss in a Latin square design with 3 to 7 days between doses. MEASUREMENTS: All subjects completed the Multiple Sleep Latency Test (MSLT) at 9:30 AM, 11:30 AM, 1:30 PM, 3:30 PM, and 5:30 PM and a performance battery at 10:00 AM, 12:00 NOON, 2:00 PM, and 4:00 PM consisting of memory, psychomotor vigilance, and divided attention tests. RESULTS: Ethanol and sleep loss reduced the average daily sleep latency on the MSLT, both as a linear function of dose, with sleep loss in hours being 2.7 times more potent than ethanol in grams per kilogram. Ethanol and sleep loss also slowed reaction time on the psychomotor vigilance test in a linear dose-related function with the 2 being equipotent in their impairing effect. On the divided attention test, tracking deviations were increased by both ethanol and sleep loss in an equipotent and linear dose-related function. Memory recall was reduced in a linear dose-related function by both ethanol and sleep loss with ethanol being slightly more potent. Finally, sleep loss doses produced a linear decrease in self-rated quality of performance, while only at the highest ethanol dose was performance rated as poorer. CONCLUSIONS: At the studied doses, sleep loss was more potent than ethanol in its sedative effects but comparable in effects on psychomotor performance. Ethanol produced greater memory deficits, and subjects were less aware of their overall performance impairment.

Adult↗

Insomnia causes, consequences, and therapeutics: an overview.

There is growing interest in insomnia both from the perspective of recent advances in clinical management as well as research aimed at elucidating its pathophysiology. This theoretical overview of insomnia describes the negative impact, etiological considerations, and pharmacological and behavioral treatments for the disorder, with an emphasis on areas receiving increased research attention. Insomnia, the most prevalent sleep disorder, affects 10-15% of the general population. In population-based studies severe insomnia has been shown to last for a median of 4 years. In addition, insomnia has a significant negative impact on an individual's work, physical, and social performance as well as overall quality of life. Furthermore, the economic cost of insomnia related to lost productivity, work-related accidents, absenteeism, and health-care costs are enormous. There is increasing evidence linking the precipitation of insomnia to stress, and converging evidence from cognitive, endocrine, neurological, and behavioral domains provide clear evidence for hyper-arousal in insomnia. However, there remains no consensus regarding the specific etiological mechanisms of this disorder. Although the pathophysiology of primary insomnia remains an enigma, numerous treatments both pharmacological and behavioral have been developed and found to be efficacious in controlled studies. Despite the wide availability of pharmacological treatments and increased knowledge of behavioral interventions, the vast majority of individuals with insomnia do not appear to be receiving adequate treatment. The inadequate treatment of insomnia leads to several important and under-recognized consequences including subsequent development of psychiatric disease and increased substance use.

Aged↗

Hypnotics: an update.

This update reviews recent developments and advances in the therapeutic and side-effect profile of the benzodiazepine receptor agonists (BZRAs), the generally accepted drug class of choice for the symptomatic treatment of insomnia. All the approved BZRAs, depending on their pharmacokinetic profile, improve and maintain sleep. The major recent advance is in the enhanced diversity of the pharmacokinetic profiles of these drugs, and thus in the flexibility available to the clinician in treatment strategy. Also, during the past decade the nature and significance of the side effects associated with the BZRAs and their determinants, dose and half-life, have been identified and clarified. The important remaining question is whether, and how, the efficacy and safety of the BZRAs change with chronic use.

Amnesia↗

Insomnia: epidemiology, characteristics, and consequences.

Insomnia is a symptom of difficulty initiating and maintaining sleep or experiencing nonrefreshing sleep and is associated with daytime consequences. Although insomnia is typically secondary to a medical, psychiatric, circadian, or sleep disorder, it can also be a primary disorder. Primary insomnia is estimated to occur in 25% of all chronic insomnia patients. It is hypothesized to be a disorder of hyperarousal, which has been supported by research on the autonomic nervous system and hypothalamic-pituitary-adrenal axis function. Chronic insomnia is prevalent in 10% of the adult population. Age, sex, medical and psychiatric disease, and shift work all represent an increased risk of chronic insomnia. The morbidity of insomnia varies as a function of etiology. While transient insomnia produces sleepiness and impairment in psychomotor performance, chronic insomnia is associated with absenteeism, frequent accidents, memory impairment, and greater health care utilization. The most consistent impact of insomnia is a high risk of depression.

Age Distribution↗

Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

Adult↗

Nighttime versus daytime hypnotic self-administration.

RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study assessed whether insomniacs' self-administration of hypnotics extended to the daytime. METHODS: Forty-four healthy men and women, 21-55 years old, with ( n=22) and without ( n=22) insomnia volunteered. They were randomized to one of two triazolam dose groups (0.125 or 0.25 mg) and their preference for placebo versus triazolam was assessed at night (2300 hours) and day (0900 hours) over 7 consecutive days in each phase. In both night and day phases of the study, subjects received triazolam or placebo in color-coded capsules on two sampling days or nights and then were forced to choose their preferred capsule on 5 subsequent days or nights. The order of day and night study phases and the placebo and triazolam sampling days was counterbalanced. In the night phase subjects went to bed from 2330 to 0730 hours and in the day phase they were tested for level of sleepiness-alertness at 1000, 1200, 1400, and 1600 hours by the multiple sleep latency test (MSLT) and mood and performance at 1100 and 1500 hours. RESULTS: More triazolam was chosen at night than during the day. No dose differences in preferences at night versus day or between insomniacs and normals were found. Insomniacs did not differ in their triazolam preferences between night and day, while the normals chose triazolam less frequently during the day. Among insomniacs, 40% chose triazolam on >3 of the 5 days. On both screening and placebo sampling days, those with a high (>60%) daytime triazolam preference had greater average daily sleep latencies on the MSLT than those with a low (<50%) daytime triazolam preference (i.e. with a placebo preference). In the triazolam preference group, triazolam reduced daily MSLT latencies to the level of the placebo preference group. CONCLUSIONS: This study shows that the minority of insomniacs who self-administer hypnotics during the day are physiologically aroused and the drug reduces their arousal suggesting that their daytime self-administration, like their night-time self-administration, is more consistent with therapy-seeking than drug-seeking behavior, at least for the short-term.

Adult↗

Substance use for insomnia in Metropolitan Detroit.

OBJECTIVE: People with insomnia are not typically treated medically for their insomnia. Studies have reported approximately 30% of insomniacs self-medicate with alcohol or over-the-counter (OTC) medications. This study was done to identify determinants and risks of different insomnia therapeutics. METHODS: A random-digit-dial, computer-assisted survey of a representative sample of adults in Metropolitan Detroit, aged 18-65 years, is being conducted. A sample of all respondents over an 18-month period was collected (n=1324) with a 68% response rate. Exclusive past-year use of alcohol for sleep was reported by 10% (n=132), prescription medications by 8% (n=108), and OTC medications by 10% (n=135). Five percent used both alcohol and sleep medications. The three exclusive-use groups formed the comparison groups of the study. RESULTS: The prescription drug group used medications for more consecutive nights and for more total nights than the alcohol and OTC users. Alcohol users were predominantly male, while OTC and prescription drug users were predominantly female. Alcohol users were more likely to be single than the others, and prescription drug users were older than the others. Prescription drug users had more severe insomnia and had greater disability, neuroticism, and daytime fatigue than the others. In contrast, the alcohol users had greater daytime sleepiness than the others. CONCLUSIONS: In Metropolitan Detroit, insomniacs receiving medical treatment have more severe insomnia and greater disability than those who self-treat. However, while the insomnia of those self-treating is less severe, it is still associated with some risks.

Adolescent↗

Disturbed sleep predicts hypnotic self-administration.

OBJECTIVES: To evaluative whether polysomnographically determined sleep variables in a large group of subjects reflecting a wide range of sleep disturbance would be predictive of the self-administration of capsules before sleep. METHODS: Sixty-four healthy men and women with and without insomnia (aged 21-55 years) were given an opportunity to self-administer placebo or triazolam (0.25 mg) capsules (single-choice method - available capsule or no capsule) before sleep in three separate studies. All qualified using the identical criteria based on a standard nocturnal polysomnogram. Screening sleep measures then were used to predict subsequent placebo and triazolam self-administration. RESULTS: The percent of placebo and triazolam choices did not differ between or within the three studies. Persons with persistent psychophysiologic insomnia self-administered more capsules than persons with sleep state misperception or normals, with the subject groups not differing in placebo vs. active drug preference. Screening polysomnographic measures predicted percent of capsule choices. The single best predictor was the ratio of minutes of stage 3-4 sleep to minutes of wake plus stage 1 sleep with R=0.44. The addition of % stage 3-4 sleep, wake before sleep and total sleep time increased R to 0.49. On morning mood ratings less ability to concentrate and greater fatigue (Profile of Mood States) predicted percent of capsule choices with R=0.36. CONCLUSIONS: These results show that the extent of sleep disturbance predicts the likelihood of self-administering a capsule before sleep regardless of whether it is placebo or active drug.

Journal Article↗

Sleep, sleepiness, sleep disorders and alcohol use and abuse.

The study of ethanol's effects on sleep has a long history dating back to the work of Nathaniel Kleitman. This paper reviews the extensive literature describing ethanol's effects on the sleep of healthy normals and alcoholics and the newer literature that describes its interactive effects on daytime sleepiness, physiological functions during sleep, and sleep disorders. Ethanol initially improves sleep in non-alcoholics at both low and high doses with disturbance in the second half of the night sleep at high doses. Tolerance develops to the initial beneficial effects. In alcoholics sleep is disturbed both while drinking and for months of abstinence and the nature of the abstinent sleep disturbance is predictive of relapse. Ethanol interacts to exacerbate daytime sleepiness and sleep-disordered breathing, even inducing apnea in persons at risk. Ethanol's effects on other physiological functions during sleep and other sleep disorders has yet to be documented. 2001 Harcourt Publishers Ltd

Journal Article↗