Reduction In Sleep Onset Latency Research Articles

Scientific Opinion on the substantiation of health claims related to melatonin and alleviation of subjective feelings of jet lag (ID 1953), and reduction of sleep onset latency, and improvement of sleep quality (ID 1953) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

EFSA JournalVolume 8, Issue 2 1467 OpinionOpen Access Scientific Opinion on the substantiation of health claims related to melatonin and alleviation of subjective feelings of jet lag (ID 1953), and reduction of sleep onset latency, and improvement of sleep quality (ID 1953) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)Search for more papers by this author EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)Search for more papers by this author First published: 25 February 2010 https://doi.org/10.2903/j.efsa.2010.1467Citations: 6 Panel members: Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Monika Neuhéuser-Berthold, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Stephan Strobel, Inge Tetens, Daniel Tomé, Hendrik van Loveren, and Hans Verhagen. Correspondence: nda@efsa.europa.eu Acknowledgement: The Panel wishes to thank for the preparation of this opinion: The members of the Working Group on Claims: Carlo Agostoni, Jean-Louis Bresson, Susan Fairweather-Tait, Albert Flynn, Ines Golly, Marina Heinonen, Hannu Korhonen, Martinus Løvik, Ambroise Martin, Hildegard Przyrembel, Seppo Salminen, Yolanda Sanz, Sean (J.J.) Strain, Inge Tetens, Hendrik van Loveren and Hans Verhagen. The members of the Claims Sub-Working Group on Mental/Nervous System: Jacques Rigo, Astrid Schloerscheidt, Barbara Stewart-Knox, Sean (J.J.) Strain, Joachim Westenhoefer and Peter Willatts. Adoption date: 4 December 2009 Published date: 25 February 2010 Question number: EFSA-Q-2008-2686 On request from: European Commission AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume8, Issue2February 20101467 ReferencesRelatedInformation

Complementary, Holistic, and Integrative Medicine: Melatonin

1. Larissa Shamseer* 2. Sunita Vohra, MD, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, Faculty of Medicine, University of Alberta. On behalf of the American Academy of Pediatrics Section on Complementary and Integrative Medicine Melatonin is synthesized primarily in the pineal gland, although it also can be produced in the retina and gastrointestinal tract. Melatonin helps regulate circadian rhythms, specifically sleep-wake cycles. These cycles are under the control of the suprachiasmatic nucleus, through which patterns of light and darkness are transferred from the retina to the pineal gland. Melatonin is formed from the essential amino acid tryptophan via serotonin, based on specific patterns. Simply stated, in the presence of light, melatonin production is inhibited; in the darkness, it is synthesized. Melatonin also can be taken as an exogenous supplement, which is synthesized to be chemically identical to its endogenous counterpart, and is classified as a natural health product by Health Canada or dietary supplement by the United States Food and Drug Administration. Due to its involvement in the sleep cycle, exogenous melatonin has been investigated extensively for sleep disorders. Difficulties initiating and maintaining sleep affect 15% to 25% of the pediatric population. Thirty minutes is believed to be the normal time to initiate sleep or sleep onset latency (SOL), which is defined as the amount of time between the person laying down to sleep and the onset of stage 1 sleep. (1)(2)(3)(4) A difference of 15 minutes in SOL typically is considered clinically important. (4) The literature evaluating melatonin for the treatment of sleep disorders was reviewed systematically in 2004 by the Agency for Healthcare Research and Quality (AHRQ). (5) Efficacy reports of melatonin for primary and secondary sleep disorders, including examination of pediatric subgroups, appeared in subsequent publications following the AHRQ report. Findings indicate that melatonin may be safe and effective for managing some primary (Table 1) and secondary (Table 2) sleep disorders. | Author and Year | Study Design | Population | Intervention/Control | Dose/Frequency/Duration | Outcome | |:----------------:| ------------ | -------------------------------------------------- | ------------------------- | ----------------------------------------------------- | ----------------------------------------------- | | Buscemi 2005 (6) | SR | N: 2 RCTs; 110 participants | I: Fast-release melatonin | 5 mg/once per day before bedtime/4 weeks of treatment | Reduction in SOL: 16.7 min (95% CI −29.4, −4.0) | | | | Age: 0 to 18 years | C: Identical placebo | | | | Condition: idiopathic chronic sleep-onset insomnia | | | * CI=confidence interval, RCT=randomized, controlled trial, SOL=sleep-onset latency, SR=systematic review Table 1. Study of Melatonin in …

Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study.

Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I). Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with autism. Its effectiveness remained stable for the 6-month period of administration. Melatonin was well tolerated in all patients and no side effects were noted during the therapy. Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with autism. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin in people with autism formulated.

Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study.

Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I). Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with autism. Its effectiveness remained stable for the 6-month period of administration. Melatonin was well tolerated in all patients and no side effects were noted during the therapy. Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with autism. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin in people with autism formulated.

Sueño y mujer

There is a strong link between female sex hormones and sleep. This implies the existence of sex differences both in the structure of sleep as in the incidence of various sleep disorders. To review the changes in the pattern of sleep experienced by women along different stages of their life cycle (fertile period, menstruation, pregnancy, menopause and postmenopause), as well as the most frequent sleeping pathologies in which there exist more gender differences (insomnia, obstructive sleep apnea syndrome, restless legs syndrome and narcolepsy). About normal sleeping has been reported a higher quality of it, in women compared with men (increased sleeping time, reduced sleep onset latency, and a greater efficiency of sleeping), but they frequently complain of sleep problems. Moreover, different stages in the life of women are associated with significant physiological and hormonal changes that favour the disruption of normal sleep pattern and by this way, possibly, increase risk to suffer sleep disorders. The reasons that underlie in gender differences in sleeping disorders are attributed to differences in normal sleep pattern, in the clinical manifestations and risk factors for sleep disorders, and in the results and optimal dose of treatments.

P03-224 Melatonin in treatment of chronic sleep disorders in adults with pervasive development disorders: A retrospective study

Background:Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. the evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with intellectual disability.Methods:This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with pervasive developmental disorders. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3mg/2weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included the Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I).Results:Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with pervasive developmental disorders. Its effectiveness remained stable for the 6-months period of administration. Melatonin was well-tolerated in all patients and no side effects were noted during the therapy.Conclusions:Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with intellectual disability. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin for people with ID formulated.

Short-term treatment with gaboxadol improves sleep maintenance and enhances slow wave sleep in adult patients with primary insomnia

Gaboxadol is a selective extrasynaptic GABA(A) agonist, previously in development for the treatment of insomniac patients. To evaluate the acute efficacy and safety of gaboxadol in primary insomnia (PI). This was a randomised, double-blind, four-way crossover, polysomnograph study comparing gaboxadol 10 and 20 mg (GBX20) to placebo in 40 adults with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for PI. Zolpidem 10 mg was used as an active reference. Treatment was administered on two consecutive nights in each treatment session. Next-day residual effects were evaluated 2 and 9 h after lights on. Efficacy analysis included the per-protocol population (n = 38) from night 2. GBX20 reduced wake after sleep onset (p < 0.01). Both doses of gaboxadol, but not zolpidem, reduced the number of night awakenings (p < 0.001). GBX20 and zolpidem increased total sleep time (p < 0.05). Neither dose of gaboxadol nor zolpidem significantly reduced sleep onset latency, although a trend was seen for zolpidem. Gaboxadol enhanced slow wave sleep (SWS) dose-dependently (gaboxadol 10 mg: p < 0.01, GBX20: p < 0.001). Patients reported improved sleep quality following GBX20 (p < 0.05). Both doses of gaboxadol were generally well tolerated with almost exclusively mild to moderately severe adverse events (AEs). More frequent and severe AEs followed GBX20. No serious AEs were reported. No drug treatment was associated with next-day residual effects. Acute administration of gaboxadol improves sleep maintenance and enhances SWS in a dose-dependent manner in adult patients with PI. Gaboxadol was not associated with next-day residual effects. Gaboxadol was generally well tolerated, although gaboxadol showed a dose-dependent increase in incidence and severity of AEs.

Melatonin and sleep disorders associated with intellectual disability: a clinical review

Melatonin is used to treat sleep disorders in both children and adults with intellectual disability (ID), although it has no product license for such use. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with ID. A literature search was performed using multiple electronic databases. More literature was obtained from the reference lists of papers gathered through the searches. Most of the studies were uncontrolled and the few controlled trials available were of small size. Melatonin appears effective in reducing sleep onset latency and is probably effective in improving total sleep time in children and adolescents with ID. It appears to be ineffective in improving night-time awakenings. Melatonin is relatively safe for short-term use. Its safety for long-term use is not established. Potential drug interactions, possible effects on puberty and concerns regarding the use of melatonin in epilepsy, asthma and depressive disorders are discussed. Melatonin appears to be an effective sleep-initiator for children and adolescents with ID and probably has a similar effect for adults. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the ID or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin for people with ID formulated.

A Double-Blind Study in Healthy Volunteers to Assess the Effects on Sleep of Pregabalin Compared with Alprazolam and Placebo

To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers. Randomized, double-blind, placebo- and active-controlled, 3-way crossover. Single research center. Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days. Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments. Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.

Cutaneous warming promotes sleep onset

Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining. This decline is mainly due to an increase in skin blood flow and consequently skin warming and heat loss. We have proposed that these intrinsically occurring changes in core and skin temperatures could modulate neuronal activity in sleep-regulating brain areas (Van Someren EJW, Chronobiol Int 17: 313-54, 2000). We here provide results compatible with this hypothesis. We obtained 144 sleep-onset latencies while directly manipulating core and skin temperatures within the comfortable range in eight healthy subjects under controlled conditions. The induction of a proximal skin temperature difference of only 0.78 +/- 0.03 degrees C (mean +/- SE) around a mean of 35.13 +/- 0.11 degrees C changed sleep-onset latency by 26%, i.e., by 3.09 minutes [95% confidence interval (CI), 1.91 to 4.28] around a mean of 11.85 min (CI, 9.74 to 14.41), with faster sleep onsets when the proximal skin was warmed. The reduction in sleep-onset latency occurred despite a small but significant decrease in subjective comfort during proximal skin warming. The induction of changes in core temperature (delta = 0.20 +/- 0.02 degrees C) and distal skin temperature (delta = 0.74 +/- 0.05 degrees C) were ineffective. Previous studies have demonstrated correlations between skin temperature and sleep-onset latency. Also, sleep disruption by ambient temperatures that activate thermoregulatory defense mechanisms has been shown. The present study is the first to experimentally demonstrate a causal contribution to sleep-onset latency of skin temperature manipulations within the normal nocturnal fluctuation range. Circadian and sleep-appetitive behavior-induced variations in skin temperature might act as an input signal to sleep-regulating systems.

SLEEP DISTURBANCE IN BATTERED WOMEN LIVING IN TRANSITIONAL HOUSING

This study describes objective and subjective sleep in a convenience sample of 29 battered women living in specialized transitional housing programs compared to 30 women living in their own stable home environment. Compared to healthy controls, battered women living in transitional housing experienced longer sleep onset latencies by both subjective and objective measures and higher percentage of time awake during the night by objective measure. Poor sleep quality may reflect the relative contributions of less total sleep time, difficulty falling asleep, and more awakenings during the night rather than just one aspect of disturbed sleep. Findings suggest that battered women in transitional housing programs may improve daytime alertness and benefit from interventions directed toward reducing sleep onset latency as well as increasing total sleep time.

Effects of exogenous melatonin on sleep: a meta-analysis

Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age. However, existing studies on the soporific efficacy of melatonin have been highly heterogeneous in regard to inclusion and exclusion criteria, measures to evaluate insomnia, doses of the medication, and routes of administration. We reviewed and analyzed (by meta-analysis) available information on effects of exogenous melatonin on sleep. A MEDLINE search (1980 to December 2003) provided English-language articles, supplemented by personal files maintained by the authors. The analysis used information derived from 17 different studies (involving 284 subjects) that satisfied inclusion criteria. Sleep onset latency, total sleep duration, and sleep efficiency were selected as the outcome measures. The study effect size was taken to be the difference between the response on placebo and the mean response on melatonin for each outcome measured. Melatonin treatment significantly reduced sleep onset latency by 4.0 min (95% CI 2.5, 5.4); increased sleep efficiency by 2.2% (95% CI 0.2, 4.2), and increased total sleep duration by 12.8 min (95% CI 2.9, 22.8). Since 15 of the 17 studies enrolled healthy subjects or people with no relevant medical condition other than insomnia, the analysis was also done including only these 15 studies. The sleep onset results were changed to 3.9 min (95% CI (2.5, 5.4)); sleep efficiency increased to 3.1% (95% CI (0.7, 5.5)); sleep duration increased to 13.7 min (95% CI (3.1, 24.3)).

Therapy of insomnia in heroin patients

Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomised, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders.An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep wake syndrome in people who are blind, and rapid eye movement-behaviour disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep.A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomised and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p < 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo.These findings highlight the potential importance of melatonin in treating certain first degree sleep disorders. The development of large-scale, randomised, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.

Use of night-time benzodiazepines in an elderly inpatient population.

To examine benzodiazepine prescribing for sleep induction in an elderly medical inpatient population to determine if hospital prescribing may have encouraged benzodiazepine use following discharge. Secondary objectives included assessment of quality of sleep in hospital compared with home and monitoring for possible benzodiazepine side-effects. Inpatient and discharge prescribing of benzodiazepines used for sleep induction were recorded in two medical wards over a 3-month period. A questionnaire was used to obtain information on patients' sleep patterns at home and in hospital. A follow-up telephone survey at 2-3 weeks post-discharge was made for those patients who were prescribed benzodiazepine at discharge. Benzodiazepines were prescribed for 20% of patients with 94% of prescriptions being for temazepam. Of the 54 patients prescribed benzodiazepines during admission, 57% were not taking a benzodiazepine at home prior to their hospital admission. At discharge, 14 patients were prescribed benzodiazepines for home use, eight of whom had not used them at home previously. On follow-up none of these eight patients expressed a desire to continue benzodiazepine use for sleep induction. There was a significant (P < 0.05) reduction in sleep onset latency and number of nocturnal awakenings in hospital when compared with home. There was no change in sleep duration and overall quality of sleep. There was an association between early morning insomnia and benzodiazepine use. Discharge prescribing of benzodiazepines was appropriately limited to temazepam and did not encourage home use in previous non-users. Benzodiazepines (primarily temazepam) were effective in the short term for inducing sleep in the hospital setting, with little evidence of side-effects.

Can normal subjects be motivated to fall asleep faster?

The Multiple Sleep Latency Test (MSLT) is widely believed to offer an objective, physiological measure of sleepiness. The speed with which a person falls asleep throughout the day is understood to be related systematically to sleep need and circadian phase. This study examined whether normal subjects ( n = 14 young female adults) could achieve faster MSLT sleep onsets if they were given the incentive to do so. During week 1 baseline MSLTs were determined over 1 day for all subjects. In week 2 they were randomly assigned to two groups. Control subjects underwent a second MSLT testing day identical to that of week 1, whereas Incentive subjects had an additional financial incentive to sleep. There was a significant reduction in sleep onset latency (indicating increased sleepiness) during the 1500 h trial following the incentive, when subjects also reported a significantly greater increase in sleepiness over the trial. These findings suggest that when coupled with a mid-afternoon increase in sleepiness, increased motivation to sleep can reduce sleep onset latency.

Sleepiness after glucose in narcolepsy.

The issue of whether a high carbohydrate intake affects sleepiness and sleep variables has been studied in normals but not in patients suffering from narcolepsy, despite anecdotal evidence that sugars may facilitate sleepiness in this population. This study investigated whether the intake of 50 g glucose exacerbated sleepiness in narcolepsy subjects. A double-blind cross-over study, involving 12 narcolepsy subjects and 12 matched controls, measured behaviour after a light lunch supplemented with a drink of either 50 g glucose or placebo (artificially sweetened drink). The main dependent variables were the performance and EEG measures from the Wilkinson Auditory Vigilance Task (WAVT) and sleep variables from a 45 minute nap. The results indicate that in the narcolepsy subjects glucose was associated with decreased wake duration, reduced sleep onset latency and more spontaneous and induced sleep stage changes during the WAVT, while the nap revealed an increased intensity of sleepiness after glucose as measured by the Polygraphic Score of Sleepiness. Eleven of the twelve narcolepsy subjects showed increased REM duration in the nap after glucose. The findings are discussed in relation to serotonin synthesis, basal sleepiness and possible irregularities in the action of insulin.

Home-based central nervous system assessment of a multifactor behavioral intervention for chronic sleep-onset insomnia

The majority of individuals with insomnia treated with single behavioral interventions do not achieve normal sleep. In this study, individuals with chronic sleep-onset insomnia (n=12) were treated with a sequentially administered multifactor behavioral intervention consisting of sleep restriction, modified stimulus control, and relaxation training. They were compared to age- and sex-matched normal sleepers (n=14) prior to and following treatment using home-based polysomnography and power spectral analysis of pre-sleep EEG activity as dependent measures. Individuals with insomnia showed highly significant beneficial changes on EEG measures of insomnia, including a 75% reduction in sleep-onset latency, and did not differ from normal sleepers at posttreatment. Individuals with insomnia exhibited greater pre-sleep CNS arousal than normal sleepers at pretreatment and showed a significant reduction on this measure at posttreatment. Objective improvements in sleep were accompanied by significant improvements in self-report measures of sleep and mood. We conclude that a multifactor behavioral intervention consisting of sleep restriction, modified stimulus control, and relaxation response training is highly effective in moving individuals with chronic sleep-onset insomnia into the range of normal sleepers and may achieve its effect, in part, by reducing pre-sleep CNS arousal.

The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice.

The safety and efficacy of 10 or 20 mg/day zolpidem, a new hypnotic belonging to the imidazopyridine class, were studied over a 180-day period in 96 patients with sleep disorders. The treatment was continued for a further 180 days by 49 of these patients. Follow-up information from 21 patients who discontinued treatment after 180 days showed no rebound insomnia or withdrawal signs. Efficacy of treatment with respect to reduction of sleep onset latency and number of nocturnal wakenings, and improvement in duration of sleep, quality of sleep and morning wakenings was found in nearly 90% of patients and was maintained in those patients who continued treatment for 360 days. This efficacy was achieved with a stable percentage of patients receiving 10 mg/day and 20 mg/day zolpidem from day 30 to the final visit. Zolpidem, therefore, has been shown to be an effective and safe hypnotic, and to be devoid of rebound and withdrawal effects.

Acute effects of hydroxyzine on nocturnal sleep and sleep tendency the following day: A C‐EEG study

AbstractThe acute hypnotic effects of hydroxyzine 25 mg and 50 mg nocte, were examined in six male and six female volunteers. Continuous electrophysiological measures (C‐EEG) were taken to assess both nocturnal sleep and sleep tendency the following day. Both doses produced significant reductions in sleep onset latency and decreases in waking during sleep; reciprocal increases in sleep duration were also seen. Female subjects demonstrated a greater hypnotic response, including a dose‐dependent decrease in sleep onset latency. Increases in sleep duration following both doses were significant for the female group alone. C‐EEG measures of increased drowsiness the following day failed to achieve significance; although the largest effects on daytime sleepiness, including dose‐dependent increases, were again seen with the female subject group and corresponded with subjective ratings. These results demonstrate the hypnotic efficacy of hydroxyzine whilst failing to detect significant C‐EEG hangover effects. However, variability in response to antihistamines, registered here as differences between the sexes, requires further consideration.

Hypnopolygraphic alterations in attention deficit disorder (ADD) children

The sleep pattern of 13 prepubertal children, nonmedicated, rigourously diagnosed as Attention Deficit Disorder (ADD) was recorded for two consecutive nights. Analyses of sleep pattern variables revealed a marked reduction of sleep onset latency (p less than .01), a great number of nocturnal awakenings (p less than .01), and a high increase of Delta sleep percentage (p less than .01) for the ADD children compared to normals. In addition, the two subtypes of the disorder--ADD with hyperactivity (ADD/H) and ADD without hyperactivity (ADD/WO) or ADD undifferentiated--showed distinct hypnopolygraphic correlates. Those ADD/H children had a greater sleep fragmentation and a lesser degree of sleep efficiency. These findings would support the hypothesis that ADD is related to a deficient control of arousal level and, on the other hand, suggest that ADD/H and ADD/WO are different clinical entities.