Sleep Initiation and Maintenance Disorders: Roehrs T

Roth T, Roehrs T, Pies R. · Sleep Disorders and Research Center, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. · Sleep Med Rev. · Pubmed #17175184 No free full text.

Abstract: Interest in developing a greater understanding of the pathophysiogical mechanisms underlying primary insomnia has increased. Recent evidence indicates that there may be some neuroendocrine and clinical similarities between primary insomnia and major depressive disorder, that abnormal corticotropin releasing factor (CRF) activity occurs in major depression, and that CRF hyperactivity appears to mediate the hyperarousal seen in primary insomnia. These findings all point to the possibility of hypothalamic-pituitary-adrenal (HPA) axis and CRF overactivity in both disorders. More recent findings have strengthened the evidence that primary insomnia may be linked with mood disorders and is associated with HPA axis overactivity and excess secretion of CRF, adrenocorticotropin releasing hormone, and cortisol. These insights have implications for managing chronic primary insomnia, such as use of antiglucocorticoid agents.

Bonnet MH, Balkin TJ, Dinges DF, Roehrs T, Rogers NL, Wesensten NJ, Anonymous00034. · Dayton Department of Veterans Affairs Medical Center, Wright State University, and Kettering Medical Center, Dayton, OH 45428, USA. · Sleep. · Pubmed #16268386 No free full text.

This publication has no abstract.

Drake CL, Roehrs T, Roth T. · Henry Ford Hospital Sleep Disorders and Research Center, CFP3, Detroit, Michigan 48202, USA. · Depress Anxiety. · Pubmed #14661186 No free full text.

Abstract: 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.

Roth T, Roehrs T. · Division of Sleep Medicine, Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan, USA. · Clin Cornerstone. · Pubmed #14626537 No free full text.

Abstract: 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.

Roehrs T, Roth T. · Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. · Curr Neurol Neurosci Rep. · Pubmed #12583849 No free full text.

Abstract: 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.

Roehrs T, Bonahoom A, Pedrosi B, Zorick F, Roth T. · Henry Ford Hospital, Sleep Disorders and Research Center, 2799 West Grand Boulevard, CFP-3, Detroit, MI 48202, USA. · Psychopharmacology (Berl). · Pubmed #11981593 No free full text.

Abstract: 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.

Roehrs T, Bonahoom A, Pedrosi B, Rosenthal L, Roth T. · Henry Ford Hospital, Sleep Disorders and Research Center, 2799 West Grand Blvd, Detroit, MI 48202, USA. · Psychopharmacology (Berl). · Pubmed #11374329 No free full text.

Abstract: RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study determined whether prior experience with different treatment regimens (i.e., instructions and capsule availability) would alter the previously observed high hypnotic self-administration rates. METHODS: Sixty-four healthy men and women with (n = 32) and without (n = 32) insomnia, 21-55 years, self administered placebo or triazolam (0.25 mg) after different prior treatment regimens. They received one of three different treatment regimens enforced for 11 nights: a capsule each night, a capsule as needed, or a capsule every third night. On 14 subsequent nights they choose to self-administer a capsule or not, placebo during 1 week and triazolam (0.25 mg) the other (counterbalanced in order). RESULTS: Insomniacs self-administered more capsules than normals and triazolam was self-administered more than placebo. For both groups, treatment regimen had a minimal effect on capsule self-administration. During the treatment phase, triazolam improved self-ratings of sleep relative to placebo. During the choice phase, nightly variations in self-rated sleep predicted self-administration of a capsule on the following night, regardless of whether the capsule was active drug or placebo. CONCLUSIONS: The data of this study are consistent with the view that hypnotic self-administration by insomniacs is therapy-seeking behavior and not drug abuse.

Roehrs T, Turner L, Roth T. · Henry Ford Hospital, Sleep Disorders and Research Center and Department of Psychiatry and Behavioral Neuroscience, Wayne State University, School of Medicine, Detroit MI 48202, USA. · Sleep. · Pubmed #11007446 No free full text.

Abstract: STUDY OBJECTIVES: To assess the effect of sleep loss and the effect of a sedating drug on waking actigraphy DESIGN: N/A SETTING: N/A PARTICIPANTS: Seventeen healthy volunteers, aged 19-35 yrs Interventions: Four night-day treatments presented in a Latin Square Design: placebo-8 hr time-in-bed (TIB), placebo-4 hr TIB, placebo-0 hr TIB, and diphenhydramine 50 mg-8 hr TIB. MEASUREMENTS AND RESULTS: After the appropriate TIB, medication was administered at 09:00 hr, the Multiple Sleep Latency Test at 09:30, 11:30, 13:30, 15:30, and 17:30 hr, and a 45 min performance battery at 10:30, 14:30, and 16:30 hr. Each day the volunteers wore actigraphs from 0700-1800 hrs. Decreasing TIB was associated with decreased daily mean sleep latency on the MSLT with 4 and 0 hrs differing from 8 hrs and each other. Daytime activity also was reduced by the reduced prior TIB. Increased inactivity relative to the 8 hr TIB developed between the 4 hr and 0 hr TIBs, with 4 hrs differing from 0 hrs, but not 8 hrs. Diphenhydramine 50 mg reduced mean daily sleep latency and increased percent inactive time relative to placebo. On the MSLT diphenhydramine was intermediate to 4 hr and 0 hr TIB and on actigraphy it was similar to 0 hr TIB. CONCLUSIONS: The difference in the effect of diphenhydramine on these actigraphy and MSLT may reflect the different sensitivities of the measures.

Roehrs T, Papineau K, Rosenthal L, Roth T. · Sleep Disorders & Research Center, Henry Ford Hospital, Detroit, Michigan, USA. · Neuropsychopharmacology. · Pubmed #10063488 links to  free full text

Abstract: The purpose of this study was to assess the effects of low ethanol doses on sleep and mood and to assess its reinforcing effects used as a hypnotic. Twenty healthy adults, aged 21-45 yrs, all moderate social drinkers, were studied: eleven subjects had insomnia and nine were normal sleepers, as documented by clinical polysomnography. On two sampling nights each, ethanol (0.5 g/kg) or placebo was administered before sleep in color-coded cups presented in three doses (0.2, 0.2, and 0.1 g/kg) separated by 15 min. On three subsequent nights subjects chose their preferred presleep beverage (0.2 g/kg ethanol or placebo) based on cup color and were given an opportunity for 3 additional refills (0.2 g/kg each) of the chosen beverage at 15 min intervals, yielding a total possible dose of 0.8 g/kg. Insomniacs chose ethanol 67% of nights and normals 22%. Insomniacs chose significantly more ethanol refills than normals for an average nightly dose of 0.45 g/kg and normals took significantly more placebo refills. On the sampling nights 0.5 g/kg ethanol reduced REM sleep for both groups for the 8-hr sleep period and in insomniacs increased stage 3-4 sleep and reduced stage 1 sleep during the first half of the night to the level seen in the normals. Other sleep variables were not altered in either group or halves of the night. Presleep improvements in the Profile of Mood States tension and concentration factors were also associated with ethanol administration. Thus, acutely, both sleep and mood effects appear to be associated with the reinforcing effects of ethanol as a hypnotic for insomniacs.

Drake CL, Jefferson C, Roehrs T, Roth T. · Henry Ford Hospital Sleep Disorders and Research Center, and Department of Psychiatry and Behavioral Neurosciences, Wayne State College of Medicine, Detroit, MI 48202, USA. · Sleep Med. · Pubmed #16996309 links to  free full text

Abstract: BACKGROUND AND PURPOSE: To determine the sleep response to caffeine in individuals vulnerable to stress-related sleep disturbance as measured by polysomnography. PATIENTS AND METHODS: Eleven healthy individuals without insomnia scoring low (4 women, mean age=32.64+/-15.46 years) and 10 healthy individuals also without insomnia scoring high (6 women, mean age=34.20+/-13.73 years) on a measure of vulnerability to stress-related sleep disturbance were studied in a laboratory protocol. A moderate-low dose of caffeine (3 mg/kg) was administered 1h prior to lights-out and compared to a counterbalanced control night with each condition separated by 1 week. Standard polysomnographic measures were assessed (i.e. total sleep time, sleep efficiency, latency to persistent sleep, and sleep stage percentages) for both control and caffeine nights. RESULTS: There were no between-group differences in sleep on the control night. Importantly, individuals reporting vulnerability to stress-related sleep disturbance had significantly prolonged latency to persistent sleep in response to the caffeine challenge (interaction; P<0.05). CONCLUSION: Normal sleepers with an identified vulnerability to stress-induced sleep disturbance exhibited greater objectively verifiable sleep-reactivity in response to a caffeine challenge compared to non-vulnerable individuals. These results suggest that the construct of individual differences in vulnerability to sleep disturbance applies to a pharmacological 'stressor' (i.e. caffeine) as well as to previously assessed stressors such as a first-night effect. This finding provides further support for generalized trait vulnerability by demonstrating a sleep disturbance to a wake-promoting pharmacological challenge in specific a priori identified individuals.

Jefferson CD, Drake CL, Scofield HM, Myers E, McClure T, Roehrs T, Roth T. · Henry Ford Hospital Sleep Disorders and Research Center, Detroit, MI, USA. · Sleep. · Pubmed #16171275 No free full text.

Abstract: STUDY OBJECTIVES: The present study was designed to assess selected aspects of sleep hygiene from a population-based sample of individuals with insomnia compared to age- and sex-matched controls. DESIGN: A random-sample phone survey of 258 individuals meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based criteria for insomnia was compared to age- and sex-matched normal sleepers on specific measures of sleep hygiene. Sleep hygiene practices measured included cigarette smoking, smoking near bedtime, alcohol use, caffeine use, napping, time in bed, and reported likelihood of sleeping in on weekends. SETTING: Detroit tricounty population. PARTICIPANTS: 258 individuals 18 to 65 years old with insomnia and 258 age- and sex-matched controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Insomniacs reported poorer sleep hygiene, as evidenced by an increase in prevalence of smoking close to bedtime and increased use of alcohol. They also reported more naps per week and sleeping in on days not worked. Caffeine use did not differ between groups. Time in bed was also comparable between insomniacs and controls. CONCLUSION: Insomniacs do engage in specific poor sleep hygiene practices, such as smoking and drinking alcohol just before bedtime. These particular aspects of sleep hygiene may be important components that exacerbate or perpetuate insomnia.

Roehrs T, Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202, USA. · Sleep Med. · Pubmed #15341891 No free full text.

Abstract: BACKGROUND AND PURPOSE: Medical treatment of insomnia has declined over the past decade and, when treated, use of non-hypnotic medications has increased. This study assessed the characteristics of the prescriptions for insomnia and of the patients receiving those prescriptions. PATIENTS AND METHODS: The outpatient pharmacy database of the Henry Ford Hospital, Health Alliance Plan (HAP) was searched from 1/1/98 to 6/30/99 for mentions of the 10 most frequently used drugs for the treatment of insomnia listed in the National Disease and Therapeutic Index for 1987-1996. The 10 drugs were alprazolam, amitriptyline, clonazepam, doxepin, flurazepam, lorazepam, temazepam, trazodone, triazolam, and zolpidem. These were classified by their indication as antidepressant, anxiolytic, or hypnotic and the three indication groupings were compared on patient and prescription characteristics. RESULTS: Over the 18 month period the total patient population covered by HAP was 287,456; 20,014 (7%) patients received one or more prescriptions for insomnia. Of these, anxiolytics were most frequently prescribed (55%), then antidepressants (25%), and hypnotics least frequently (20%). Patients receiving hypnotics were more likely to be male, older, and to receive a narrower dose range, in smaller quantities and with fewer refills than patients receiving anxiolytics or antidepressants. CONCLUSIONS: In this large managed-care population, hypnotics are prescribed conservatively, while the non-hypnotics, for which there is limited efficacy and safety data, are prescribed on a more chronic basis.

Drake C, Richardson G, Roehrs T, Scofield H, Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA. · Sleep. · Pubmed #15124724 No free full text.

Abstract: STUDY OBJECTIVES: To determine the presence of a hypothesized trait vulnerability to sleep disturbance and hyperarousal. DESIGN: Polysomnographic assessment of sleep in response to stress during a first night in the laboratory and subsequent physiologic arousal. PARTICIPANTS: One hundred and four individuals (46% men, mean age 40.4 +/- 12.9 years) drawn from a population-based sample. INTERVENTIONS: Individuals were exposed to a first night in the laboratory. MEASUREMENTS AND RESULTS: Participants completed a Likert-scale questionnaire, consisting of 27 items, that assesses sleep disturbance in response to commonly experienced stressful situations. Factor analytic techniques identified a single 9-item factor that was representative of the construct of "stress-related" vulnerability to sleep disturbance. Reliability of the resulting 9-item scale was high (Cronbach's alpha = .83). Individuals with higher scores on this scale, the Ford Insomnia Response to Stress Test (FIRST; median split), had a lower sleep efficiency (P = .001), as well as an increased latency to stage 1 sleep (P = .001) and persistent sleep (P = .002) on the first night of nocturnal polysomnography. Moreover, these high-scoring individuals showed increased arousal as evidenced by an elevated sleep latency on the Multiple Sleep Latency Test compared to individuals with low FIRST scores. Importantly, after controlling for current and past insomnia, the differences between individuals scoring high and low on the FIRST in terms of nocturnal sleep and daytime arousal remained significant. Other stages of sleep (stage 2, slow-wave, and rapid eye movement sleep) were not different between the groups. CONCLUSIONS: These results showing a relationship between FIRST scores and nocturnal polysomnography and Multiple Sleep Latency Test scores have 3 potential implications: (1) the data demonstrate a characteristic that relates to vulnerability to stress-related sleep disturbance as manifested by a first night in the laboratory; (2) the elevated latencies on the Multiple Sleep Latency Test in these individuals, despite significantly disturbed sleep, support the notion of physiologic hyperarousal in these individuals and suggests they may be predisposed to developing chronic primary insomnia; and (3) the vulnerability identified may underlie vulnerability to transient sleep disturbance associated with other sleep-disruptive factors.

Roehrs T, Hollebeek E, Drake C, Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, and Department of Psychiatry and Behavioral Neuroscience, School of Medicine, Wayne State University, Detroit, MI, USA. · J Psychosom Res. · Pubmed #12127173 No free full text.

Abstract: 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.

Stepanski E, Zorick F, Roehrs T, Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA. · Sleep. · Pubmed #10737338 No free full text.

Abstract: STUDY OBJECTIVES: This study investigated changes in MSLT scores and recovery sleep following total sleep deprivation in subjects with insomnia as compared to normal sleepers. DESIGN: Matched-groups design. SETTING: A sleep disorders center in a large medical center. PARTICIPANTS: Ten individuals with psychophysiological insomnia and ten age- and sex-matched normal sleepers served as subjects. INTERVENTIONS: Subjects underwent total sleep deprivation after baseline polysomnography and MSLT. A post-deprivation MSLT was obtained, as well as polysomnography on the recovery night and an MSLT after the recovery night. MEASUREMENTS AND RESULTS: Both groups showed significant decreases in MSLT scores following total sleep deprivation, as compared to baseline. Both groups had significantly shorter scores on a nighttime MSLT compared to a daytime MSLT. The insomnia group also showed a significant increase in total sleep time on the recovery night compared to baseline. CONCLUSIONS: The MSLT is sensitive to changes in sleepiness associated with total sleep deprivation in individuals with primary insomnia.

Mendelson WB, Roth T, Cassella J, Roehrs T, Walsh JK, Woods JH, Buysse DJ, Meyer RE. · · Sleep Med Rev. · Pubmed #15062207 No free full text.

Abstract: 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.