The economic costs of insomnia comorbid with depression and anxiety disorders: an observational study at a sleep clinic in Mexico.

Significant advances documenting the costs associated with insomnia have been achieved. However, those related to insomnia associated with mood disorders remain understudied, even though insomnia is more severe in the presence of comorbid conditions such as depression and anxiety. The aim of this study was to determine the direct and indirect costs of insomnia associated with depression and anxiety disorders (DAD) from the perspective of the patient in a private healthcare system. This was an observational study of chronic insomnia associated with DAD at a private Sleep Disorders Clinic in Mexico City between 2019 and 2020. Patients were followed for up to one year. Healthcare resource utilization data were collected through clinical records. Direct and indirect costs associated with insomnia treatment were estimated through micro-costing. The estimated economic burden was projected to 5 years adjusting for inflation and discounting future costs. A deterministic sensitivity analysis was performed. The median cost of the first year of insomnia treatment associated with DAD was US$3537.57 per patient. The work productivity loss represented the highest economic burden (63.84%) followed by direct medical costs (28.32%), and the direct non-medical costs (7.85%). The estimated annual economic burden for patients treated in the private healthcare system in Mexico was US$293 million. The costs of insomnia associated with DAD at a private clinic in México were found to be high. The burden of the costs faced by these patients is substantial relative to the median income of the population. The economic costs at an individual and societal levels are substantial. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00412-6.

Parasomnias related to shift work disorder among medical residents during the first year of training in Mexico.

Shift work disorder (SWD) may affect medical residents because their workload, academic demands and extended work hours. This condition set residents at risk of more sleep disorders. The study compared parasomnias among residents with and without shift work disorder (SWD) and weighed their relative risk (RR) for each parasomnia. One hundred twenty-six residents participated in the study. The Munich Parasomnia Screening questionnaire and the Barger Questionnaire for SWD were used for the screening of parasomnias and SWD, respectively. Means and percentages of studied variables were compared between groups. Relative risk (RR) was calculated for each type of parasomnia. The more frequent parasomnias in residents with SWD the RR (and 95% confidence intervals) were: sleep terrors, 5.60 (1.84-17.01); confusional arousals, 3.73 (1.84-7.56); sleep paralysis, 3.27 (1.53-6.93); hypnagogic/hypnopompic hallucinations, 2.55 (1.03-6.28); somniloquies, 2.45 (1.21-4.92); and nightmares, 2.01 (1.54-2.62). Our data suggest that residents who experience SWD may be at risk of having lower threshold for the occurrence of rapid eye movement (REM) and non-REM (NREM) sleep parasomnias. Additional research is needed to confirm these results, and to further identify the contribution to this association.

2018 worldwide survey of health-care providers caring for patients with narcolepsy: WSS narcolepsy task force.

BACKGROUND: There are limited data available on regional differences in the diagnosis and management of narcolepsy. In order to better understand worldwide trends in clinical assessment and management of narcolepsy, a survey of health-care providers was conducted by the World Sleep Society Narcolepsy task force. METHODS: A total of 146 surveys that included items on the diagnosis and management of narcolepsy were completed by practitioners representing 37 countries. RESULTS: Most of the participants were from Europe, North America, Oceania, Asia and Latin America. A consistent approach to applying the diagnostic criteria of Narcolepsy was documented with the exception of measurement of CSF hypocretin-1, which has limited availability. While the majority of practitioners (58%) reported not using the test, 1% indicated always evaluating CSF hypocretin-1 levels. There was much variability in the availability of currently recommended medications such as sodium oxybate and pitolisant; modafinil and antidepressants were the most commonly used medications. Amphetamines were unavailable in some countries. CONCLUSION: The results of the study highlight clinical and therapeutic realities confronted by worldwide physicians in the management of narcolepsy. While the diagnostic criteria of narcolepsy rely in part on the quantification of CSF hypocretin-1, few physicians reported having incorporated this test into their routine assessment of the condition. Regional differences in the management of narcolepsy appeared to be related to geographic availability and expense of the therapeutic agents.

Understanding patient responses to insomnia.

To better gain insight into patient responses to insomnia, we take a medical anthropologically informed approach to patient beliefs and behaviors, particularly those related to self-diagnosis, management, help-seeking, and self-treatment of insomnia. We conducted 24 in-depth qualitative interviews in which participants were asked their beliefs about the origin of their insomnia, its anticipated course, their evaluation of symptoms, their responses, and their expectations surrounding treatment. Important and novel data were generated about patient beliefs and behaviors related to problem sleeping. Patients identified barriers to treatment, particularly those contextualized within a general social stigma and personal isolation, in which their problems sleeping were not taken seriously. The interview format was particularly conducive to making patients comfortable discussing the personal changes they made to their medically prescribed treatment plans, or supplanting their medical therapy with some kind of complimentary and alternative medicine (CAM) therapy. These are important issues in the long term management of chronic insomnia. We underscore concern about the need to evaluate the efficacy of therapies that so many people with insomnia are driven to try.

"Listening for his breath:" the significance of gender and partner reporting on the diagnosis, management, and treatment of obstructive sleep apnea.

In the elicitation of explanatory models for illnesses, accounts of spouses are strangely absent. This becomes critically missing information for a disorder like sleep apnea, in which a spouse or partner is often the primary agent responsible for the initial diagnosis and push to seek medical care. An apnea patient's understanding of their own illness is critically shaped less by their own direct experience of symptoms, and more by how someone else comes to experience, understand, and interpret them. Men and women, patients and partners, can vary tremendously in their decisions as to if, when, and how to either seek care for themselves, or to influence a partner to seek care. This cross-sectional, exploratory, mixed-methods study from the Dallas metropolitan area, USA, was done in 2006 to illuminate the significance of gender and partner-reporting in shaping the lay diagnosis, management, and treatment of obstructive sleep apnea. Patients clinically diagnosed with sleep apnea were recruited by a physician; a medical anthropologist then arranged in-depth, semi-structured interviews with both patients and partners (n = 24). Communication within relationships, along with social and cultural norms and expectations surrounding "proper" sleep for men and women, played important roles in how apnea was recognized, accepted, and acted upon by patients. More than half of men and women (patients or spouses) mention dissatisfaction with "positive airway pressure" machines, the primary treatment for obstructive apnea; partial compliance with medical advice was high, with dissatisfaction being patterned by gender. The medical anthropology of sleep disorders offers insight into traditional gender roles surrounding expected sleep and "proper" sleep roles. Given the small proportion of adults with apnea that currently see a physician for care, an expanded explanatory model involving spouses or partners promises to reveal new insight into patient behavior surrounding diagnosis, management, and treatment.

Insomnio, estrés y canabinoides / Insomnia, stress and cannabinoids

Sleep is a universal experience and a necessary ingredient to life. Young adult humans benefit from spending 8 h a day, every day, sleeping. While the function(s) of sleep is not completely understood, it is known that sleep is critical to the survival of the species. In humans, it restores alertness, helps consolidate memory and «recharge¼ cognitive abilities which are impaired at the end of the activity-phase of the cycle. Humans who do not pay their toll to sleep, for one night, for example, experience difficulties maintaining wakefulness the next day. This condition may put in danger their lives, particularly if they work in the transportation industry (i. e. taxi cabs, truck or trailers-drivers, pilots and/or operating heavy machinery among many other activities). In the past, when humans were more exposed to predators, to be sleepy in the savannah was synonymous with dying. Interestingly enough, the maladaptive strategies exhibited by a sleepy subject (which put at risk his life), are reversed by sleep. It is widely believed that sleep has a restorative function. However, what precisely is being restored during sleep remains a topic of speculation and on-going research. Sleep deprivation in humans results in cognitive deterioration and increased sleepiness, which might compromise survival as aforementioned. It is known that in rats prolonged sleep deprivation leads to death. In humans, it results in sleepiness, decreased attention, compromises memory and learning skills, and may affect motor control. The negative effects of sleep loss are reversed by recovery sleep, which may show features of delta and/or REM-sleep rebound. In this context, insomnia is a condition with known negative consequences to the health of the affected individual and frequently conveys negative effects to the family nucleus and to society in general. It has been estimated that 9% to 15% of the adult population suffers from chronic insomnia. Psychophysiologic insomnia (or primary insomnia) is likely the most prevalent type of insomnia. The patient with insomnia frequently develops an aversive response to sleep and to all aspects related to this activity. The manifestations of insomnia may include difficulty falling (and staying) asleep, frequent awakenings, early morning awakenings and/or un-refreshing quality of sleep. As a result, affected individuals frequently complain of daytime consequences such as decreased concentration, negative effects on memory (and learning), and daytime fatigue. They may also complain of headaches, fuzziness (or grogginess) and might experience manifestations of excessive sleepiness (which might represent a hazard when driving and/or operating machinery). Stress and anxiety frequently represent precipitating and/or perpetuating factors in the development of insomnia. In regards to stress, the role of the hypothalamus-pituitary-adrenal (HPA) axis in preserving homeostasis has been amply studied. The HPA axis involves the participation of peptides such as corticotropin-releasing hormone (CRH), corticotropin itself and cortisol. The autonomic nervous system activates the amygdaloid complex further enhancing the stress response. When patients are unable to control their stress response, the magnified response may be manifested as an anxiety disorder. According to the DSM-IV, the diagnosis of generalized anxiety disorder (GAD) is based on persistent symptoms of excessive anxiety and worry. Patients with GAD as well as those suffering from other anxiety disorders such as PTSD and panic attacks may manifest symptoms of insomnia. Several models of stress have been proposed to better understand these conditions. For example, prenatal stress has been suggested to increase vulnerability to life events and some reports have suggested impaired sleep among some of the animal models that have been studied. Specifically, it has been reported that rats who are deprived of maternal care suffer from dysregulation of the orexinergic system. Consequently, affected rats may have manifestations of sleep-wake dysregulation. There is more. Rats born to a low care maternal provider (which induces an early stress response) have been found to have methylated the gene that encodes the glucocorticoid receptors, which is reflected in a low expression of receptors. As a result, these animals release more corticosterone in response to stressful situations and are less efficient in managing stress. Furthermore, they have a lower expression of the CB1 receptor in several areas of the brain, thus suggesting that the systems responsible for reducing excitability of the brain (and consequently reducing the subjective sensation of fear and anxiety) are shattered. Models of insomnia evaluating the possible role of an inadequate stress-response have not been thoroughly studied. Potential pharmacologic interventions using such a theoretical framework have not been systematically studied and thus offer a venue for novel pharmacological interventions. The addition of new therapies would be particularly useful as the clinical management of patients with chronic insomnia remains a challenging area in medical practice. This despite the availability of multiple approved hypnotic medications in the physician's armamentarium. To date there is no hypnotic medication which can be considered ideal for the treatment of chronic insomnia. Issues of tolerance and dependence remain relevant concerns for those hypnotic medications, which are considered most effective in the treatment of this condition. Research identifying new compounds based on molecules whose physiologic action is to induce sleep may render safer, more efficient pharmacological interventions to treat insomnia. Following this line of thinking, we have tested the effects of endocannabinoids (eCBs). The eCBs represent a family of molecules, lipids in nature, which bind to the same receptors to which marijuana is known to bind. The active metabolite of marijuana (delta-9-tetrahydrocannabinol [THC]) is known to bind to the CB1 receptors and produce a series of effects including relaxation and sleep. Following the discovery of several eCBs by the research groups of Mechoulam and Lerner, we have tested anandamide and oleamide as sleep inducers. Results have indicated that both molecules and a third one, 2-arachidonyl glycerol, induce sleep (mainly REM sleep). In the present review insomnia is speculated to be a consequence of chronic stress. Several animal models of early stress are also discussed to better understand the role of stress in the causation of insomnia. The current limitations in the availability of ideal hypnotic medications prompt us to argue in favor of continued efforts to find additional, novel pharmacologic interventions to treat this condition. In this context, the potential use of endocannabinoid compounds is proposed as a possible new line of hypnotic medications. While eCBs have been used so far only in animal models, they have been amply successful in promoting the expression of non-REM and REM sleep. The endocannabinoid system has the potential to induce sleep and thus suggest that endocannabinoid agonists offer a new research venue for the exploration of novel pharmacologic interventions in the treatment of insomnia.

El sueño es una actividad fundamental para el bienestar y la preservación del la salud. El no dormir resulta en consecuencias potencialmente letales. Por ejemplo, ratas experimentalmente privadas de sueño total (o de sueño MOR) mueren al cabo de algunas semanas de experimentación. Asimismo, en humanos, la privación de tan solo una noche de sueño conlleva consecuencias importantes. Hipersomnolencia y disminución de las habilidades cognoscitivas son consecuencias de la privación de sueño. El individuo privado de sueño corre el riesgo de cometer errores que potencialmente pueden poner en riesgo su vida o integridad física, así como la de otros. Se ha sugerido que el sueño cumple con la muy importante tarea de ofrecer las condiciones para que se lleven a cabo diversos procesos de restauración y de reorganización neuronal así como el procesamiento de información y consolidación de la memoria. La ausencia de sueño interfiere con estos procesos con el consecuente deterioro de la conducta adaptativa del sujeto. El insomnio es un trastorno que deteriora de manera importante la calidad de vida de las personas que lo padecen. Afecta aproximadamente al 10% de la población. El insomnio se presenta en diversas formas. La clasificación internacional de los trastornos del dormir considera 11 tipos de insomnio. Entre ellos, el insomnio psicofisiológico representa el tipo de insomnio que más frecuentemente se manifiesta en la población. Se trata de un padecimiento donde el paciente desarrolla una aversión a dormir y a todo lo que se relacione con ello. Este tipo de insomnio tiene un componente de estrés que precipita la aparición del insomnio y puede contribuir a los elementos que ayudan a perpetuarlo (insomnio crónico). Se han desarrollado diversos modelos animales para el estudio del estrés y sus consecuencias. Por ejemplo, el estrés temprano inducido por privación del cuidado maternal. Asimismo, por inducción de estrés en la madre (rata) gestante. Sin embargo, se han explotado poco para evaluar el insomnio y mejor aún, para ensayar fármacos que puedan beneficiar al paciente insomne. A pesar de contar con una gran variedad de medicamentos hipnóticos, en la actualidad no existe un hipnótico ideal. Los tratamientos más efectivos con los que contamos conllevan riesgos importantes de tolerancia, adicción y potencialmente efectos colaterales. Por ello, la búsqueda de nuevos fármacos con propiedades inductoras de sueño es inaplazable. Especialmente de fármacos que sean capaces de inducir las fases de sueño delta y sueño MOR sin causar sonambulismo, somnolencia residual y/o efectos negativos en la memoria. En este contexto se discute el potencial uso terapéutico de los endocanabinoides (eCBs), ya que son ansiolíticos e inductores de las fases profundas de sueño (delta y sueño MOR). Los eCBs son moléculas endógenas que tienen una actividad semejante a la de la mariguana. Esto es debido a que tanto la mariguana como los eCBs afectan a un mismo receptor, que es el receptor canabinoide 1 (CB1). Los eCBs tienen un potencial terapéutico que hasta ahora no se ha explotado en beneficio de los pacientes que sufren de insomnio y/o ansiedad. Por ello, en esta revisión se analiza el insomnio desde el punto de vista clínico, se detallan sus características para que el médico clínico no experto pueda reconocerlo y potencialmente tratarlo; también se persigue subrayar la influencia potencial del estrés en la fisiopatogénesis de este trastorno. A pesar de que hay cada vez más información acerca de la síntesis y degradación de los eCBs (lo que es muy importante porque estos mecanismos pueden ser afectados por fármacos que inhiban la degradación o la faciliten, dependiendo de las necesidades terapéuticas) no discutiremos estos temas que se vuelven más especializados. Sin embargo, es importante que se conozca y se discuta su posible uso para beneficio del paciente. Esta revisión se centra en discutir los potenciales beneficios causados por la activación del receptor CB1 en el paciente insomne para reducir su dolencia de mal dormir.

Cognitive-behavioral therapy of insomnia: a clinical case series study of patients with co-morbid disorders and using hypnotic medications.

Cognitive-behavioral therapy for insomnia (CBTi) has demonstrated considerable efficacy within randomized clinical trials and case-series designs. This case-series study in a community sleep medicine clinic assessed the effectiveness of an eight-session CBTi protocol chronic insomnia patients who were allowed to continue their use of hypnotics (intent-to-treat n = 48), administered by a clinical psychology doctoral student receiving training and supervision in CBTi by a behavioral sleep medicine certified clinician. Outcome measures included daily sleep diaries, self-report measures on insomnia severity, dysfunctional beliefs and attitudes about sleep, daytime sleepiness, as well as medication usage. Patients showed significant improvements in sleep onset latency, wake time after sleep onset, sleep efficiency, insomnia severity, and dysfunctional sleep beliefs from pre- to post-treatment. No changes were seen in daytime sleepiness - patients were not excessively sleepy either before or after treatment. Use of sleep medication declined significantly from 87.5% pre-treatment to 54% post-treatment, despite no active efforts to encourage patients to withdraw. Results demonstrate that a CBTi conducted in a community sleep medicine clinic with patients not required to discontinue sleep-related medications can have similar effects as therapy delivered among those not on medication.

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

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

Longitudinal comparison study of pressure relief (C-Flex) vs. CPAP in OSA patients.

BACKGROUND: Continuous positive airway pressure (CPAP) devices with the option of flexible pressure delivery (e.g., C-Flex) are thought to provide an improved degree of comfort and result in better therapeutic adherence while maintaining standard CPAP efficacy. The purpose of this study was to compare adherence and subjective measures of comfort between C-Flex and CPAP treatment. METHODS: The study was an international, multisite, single-blinded study with participants randomized to either C-Flex or CPAP. Participants completed subjective measures of sleepiness and comfort at baseline, and at 30-, 90-, and 180-day follow-ups. Additionally, compliance data were downloaded from the device at each follow-up. Repeated measures analysis of variance was used to assess the effects of treatment. RESULTS: There were 138 men and 46 women (average age of 48 +/- 9.2, average Epworth Sleepiness Scale score of 14.9 +/- 3.6, and average diagnostic apnea/hypopnea index (AHI) of 51.9 +/- 27.7). C-Flex and CPAP groups were comparable on baseline measures, achieved comparable AHI on titration, and had comparable PAP pressure requirements. C-Flex users had comparable average hours of use per night and total nights of use across the study, but had a trend (p < .07) toward achieving greater total hours of utilization. While both groups had comparable decreases in sleepiness, C-Flex users reported on visual analog scales greater comfort (64.3 vs. 57.4; p = .01). CONCLUSIONS: The results of this study demonstrated that C-Flex has comparable resolution of respiratory indices and adherence. Furthermore, C-Flex users reported greater mask comfort.

A multicenter, prospective study of a novel nasal EPAP device in the treatment of obstructive sleep apnea: efficacy and 30-day adherence.

STUDY OBJECTIVES: Evaluate the efficacy of a novel device placed in the nares that imposes an expiratory resistance for the treatment of obstructive sleep apnea (OSA) and evaluate adherence to the device over a 30-day in-home trial period. DESIGN: One diagnostic and 3 treatment polysomnograms were administered in a Latin-square design to identify the optimal expiratory resistance to be used during the 30-day in-home trial. Subjects had repeat polysomnography with the prescribed device at the end of the 30-day trial. SETTING: Multicenter study. PARTICIPANTS: Participants (N=34; age 27 to 67) with a baseline apnea-hypopnea index (AHI) > or =5. MEASUREMENTS AND RESULTS: The AHI was reduced from 24.5 _ 23.6 (mean +/- SD) to an average of 13.5 +/- 18.7 (p < 0.001) across initial treatment nights. The AHI was 15.5 +/-+/- 18.9 (p = 0.001) for the prescribed device at the end of the 30-day trial. Of 24 subjects with an AHI > 10 at baseline, 13 achieved an AHI < 10 on the initial treatment nights; 10 had a similar response on the final treatment night. Percent of the night snoring decreased from 27.5 +/- 23.2 to 11.6 +/- 13.7 (p < 0.001) on initial treatment nights and 14.6 +/- 20.6 (p = 0.013) at the end of the trial; Epworth Sleepiness scores decreased from 8.7 +/- 4.0 at baseline to 6.9 +/- 4.4 (p < 0.001) at the end of the trial; the Pittsburgh Sleep Quality Index improved from 7.4 +/- 3.3 to 6.5 +/- 3.6 (p = 0.042). Mean oxygen saturation increased from 94.8 +/- 2.0 to 95.2 +/- 1.9 (p = 0.023) on initial treatment nights and 95.3 +/- 1.9 (p = 0.003) at the end of the trial. Sleep architecture was not affected. Participants reported using the device all night long for 94% of nights during the in-home trial. CONCLUSIONS: Treatment with this novel device was well tolerated and accepted by the participants. An overall reduction in AHI was documented; however, therapeutic response was variable among the participants. Further research is required to identify the ideal candidates for this new therapeutic option in the management of OSA.

Long-term follow-up of patients with insomnia.

It has been suggested that patients with insomnia who are lost to follow-up continue to experience symptoms. From winter 2006 to spring 2007, we contacted consecutive patients initially seen at a multidisciplinary sleep medicine clinic 3 to 5 years earlier and asked them about continuing symptoms. Among the 58 patients who agreed to participate, 43 (74%) reported that they still experienced difficulty initiating and/or maintaining sleep. Thirty-one of those patients had continued to receive treatment, 11 from a sleep medicine specialist and the remainder from other physicians. The majority listed zolpidem or eszopiclone as their primary medication, and many took multiple medications, including over-the-counter drugs and alternative medications. Most patients with insomnia were unaware of cognitive-behavioral therapy. These findings emphasize the need for primary care physicians to monitor symptoms of insomnia and to remain vigilant about potential treatment complications.

The Epworth sleepiness scale in the identification of obstructive sleep apnea.

The Epworth sleepiness scale (ESS) is often used clinically to screen for the manifestations of the behavioral morbidity associated to obstructive sleep apnea (OSA). The purpose of this study was to assess the sensitivity of the ESS in the identification of OSA, as defined by an elevated apnea-hypopnea index. A retrospective chart review of 268 consecutive patients diagnosed with OSA at a multidisciplinary sleep medicine clinic was conducted. The ESS obtained a relatively low sensitivity (66%) in the identification of an apnea-hypopnea index of 5 and above at the suggested cutoff of 10 and increased to 76% at 8. The results of the study showed only fair discriminatory ability of the ESS as a screener for OSA. A score of 8 (instead of 10) is suggested as the cutoff among clinic populations being screened for a sleep disorder.

Is sleep really for sissies? Understanding the role of work in insomnia in the US.

This study explores the role of work in patient narratives about their experiences with insomnia. "Work" includes such facets as the nature of one's occupation, the associated volume or amount of work required, mental demands related to work, work schedules and work-related stress. Interviews conducted with 24 patients aged between 22 and 74 receiving treatment for insomnia at one of two sleep medicine clinics in Oregon and Texas, USA, suggest that work is a pivotal influence in shaping interpretations of the nature of insomnia, its causes, and the efficacy of medical treatment. Results suggest correlations between sleeplessness and modern working lifestyles in American culture, in which labor seems to transcend the physical workplace, manifesting itself in the form of cognitive labor or continued problems into retirement. Patients often cite work as the primary causal agent in the development of their insomnia, their primary reason for needing "good" sleep, their impetus for seeking medical attention, and behavioral compliance with a medically prescribed regimen. Insomnia as an illness experience thus serves as a mechanism through which respondents consciously or unconsciously comment on the nature of work in their lives. The medical and social implications of these results are discussed.

The alerting effects of dexamethasone.

The purpose of this study was to characterize the level of sleepiness/alertness following the nocturnal administration of dexamethasone. Thirteen healthy men participated in this study. Following the initial screening, dexamethasone (4 mg) or placebo was administered at 22:30 hr in a randomized double-blind procedure. Subjects were given nap opportunities at 23:00, 1:00, 3:00, 4:30, 5:30, 7:30, 9:30, 11:30, 13:30, 15:30, 17:30, and 19:30 hr. The administration of dexamethasone resulted in an overall lengthening of sleep latency. Although the two groups displayed comparable latencies to stage 1 for the 23:00-7:30 hr nap opportunities, the administration of dexamethasone resulted in significantly longer latencies on the 9:30-19:30 hr nap opportunities. Consistent with these results, participants reported significantly greater levels of alertness on the Stanford Sleepiness Scale. The results of this study revealed greater levels of daytime alertness following the nocturnal administration of dexamethasone.

Psychological status and levels of sleepiness-alertness among patients with insomnia.

Are symptoms of daytime sleepiness relevant among patients with insomnia? Patients with insomnia frequently report daytime consequences secondary to their difficulty initiating and maintaining sleep. The purpose of this study was to determine the frequency of daytime sleepiness as defined by a self-reported measure of daytime sleepiness (the Epworth Sleepiness Scale). In addition, the study characterized the patients' psychological status using the Symptom Checklist-90-Revised. The study corroborated a relatively high frequency of excessive daytime sleepiness and psychiatric conditions among patients with insomnia. Furthermore, the results of the study suggest variation in psychological distress levels, according to the different levels of sleepiness/alertness.

Tolerance to daytime sedative effects of H1 antihistamines.

Sedation is the principal side effect of first generation H1 antihistamines, and recent studies have suggested that this side effect should limit the clinical application of these drugs. The sedative effect also underlies the use of these first-generation drugs as nonprescriptive remedies for insomnia. In both cases, the potential for tolerance to the sedative effect of these drugs is an important issue for which there are few objective data. In the study reported here, 15 healthy men age 18 to 50 years received either diphenhydramine 50 mg or placebo twice a day for 4 days in a randomized, double-blind, crossover trial design. Dependent measures included objective and subjective assessments of sleepiness and computer-based tests of psychomotor performance. Both objective and subjective measures of sleepiness showed significantly higher levels on day 1 for diphenhydramine compared to placebo. By day 4, however, levels of sleepiness on diphenhydramine were indistinguishable from placebo. Similarly, diphenhydramine produced significant impairment of performance that was completely reversed by day 4. These data provide the first objective confirmation that tolerance develops to the sedative effect of a prototypical first-generation H1 antihistamine, diphenhydramine. On this dosing regimen, tolerance was complete by the end of 3 days of administration. While other antihistamines and dosing regimens may differ, these results suggest that tolerance to the sedation produced by these drugs develops with remarkable rapidity.

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.