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Latest Research on Insomnia
     
J Clin Psychopharmacol. 2008 Apr;28(2):182-188.
Effects of 2-Week Treatment With Temazepam and Diphenhydramine in Elderly Insomniacs: A Randomized, Placebo-Controlled Trial.
Glass JR, Sproule BA, Herrmann N, Busto UE.
*Faculty of Pharmaceutical Sciences, University of Toronto; †Clinical Neuroscience Program, Centre for Addiction and Mental Health; ‡Faculty of Pharmacy, University of Toronto; §Clinical Research Department, Centre for Addiction and Mental Health; and ?Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

A randomized, controlled, crossover clinical study compared 14-night treatment with 15 mg temazepam, 50 mg diphenhydramine, and placebo in elderly individuals with insomnia (mean age, 73.9 years; range, 70-89 years). Primary outcome measures were subjective assessments of sleep recorded on sleep diaries. Secondary measures were the morning-after psychomotor impairment, using the digit symbol substitution task and the manual tracking task, and the morning-after memory impairment, using a free-recall procedure. Results showed sleep improvements with 15 mg temazepam compared with placebo-sleep quality (mean score, 3.3 +/- 0.9 vs 2.9 +/- 0.8; P = 0.03), total sleep time (6.9 +/- 1.0 hours vs 6.3 +/-1.3 hours; P = 0.02), number of awakenings (1.5 +/- 1.3 vs 2.0 +/- 1.2; P < 0.001), and sleep-onset latency (25 +/- 22 minutes vs 37 +/- 25 minutes; P = 0.03). Improvements were seen with diphenhydramine treatment compared with placebo on the number of awakenings only (mean, 1.7 +/- 1.1 vs 2.0 +/- 1.2; P < 0.05). Numbers of adverse events reported were similar after all treatments, although there was 1 fall during temazepam treatment. Findings indicate that temazepam is more effective than diphenhydramine when compared with placebo at the doses tested, although this advantage is mitigated by the risk of falls associated with temazepam use. The choice of agent to use in the elderly must consider these relative benefits and risks.

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J Psychiatr Res. 2008 Mar 27 [Epub ahead of print]
Nocturnal awakenings and comorbid disorders in the American general population.
Ohayon MM.
Stanford Sleep Epidemiology Research Center, Stanford University School of Medicine, 3430 West Bayshore Road, Stanford, Palo Alto, CA 94303, USA.

OBJECTIVE: Nocturnal awakenings are one of the most prevalent sleep disturbances in the general population. However, little is know about how its severity affects co-morbidity with mental disorders and organic diseases. METHODS: A representative sample consisting of 8937 non-institutionalized individuals aged 18 or over living in Texas, New York and California states were interviewed by telephone. The interviews included sleeping habits, health, sleep and mental disorders. Nocturnal awakenings were evaluated according to their frequency per week and per night, their duration and the motive(s) for the awakenings. RESULTS: A total of 35.5% of the sample reported awakening at least 3 nights per week: 23% of reported awakening at least one time every night; 4.5% 5 or 6 nights per week and 7.9% 3 or 4 nights per week. Nocturnal awakenings increased with age only among people with nightly awakenings and were more frequent among women than men only among those awakening every night.
More than 90% of subjects reported this problem lasted for more than 6 months. About 40% of subjects with nocturnal awakenings also reported other insomnia symptoms. Generally speaking, organic diseases and psychiatric disorders were more frequent among subjects waking up at least 3 nights per week regardless the frequency of nocturnal awakenings. However, nightly nocturnal awakenings were associated with more frequent organic diseases, obesity and psychiatric disorders. CONCLUSIONS: Nocturnal awakenings disrupt the sleep of about one third of the general population. Nocturnal awakenings are associated with a wide variety of organic diseases and psychiatric disorders that warrant appropriate treatment.

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Arzneimittelforschung. 2008;58(1):1-10.
Melatonergic drugs in clinical practice.
Hardeland R, Poeggeler B, Srinivasan V, Trakht I, Pandi-Perumal SR, Cardinali DP.
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, Universityof Göttingen, Göttingen, Germany. rhardel@gwdg.de

Melatonin (CAS 73-31-4) has both hypnotic and sleep/wake rhythm regulating properties. These sleep promoting actions, which are already demonstrable in healthy humans, have been found useful in subjects suffering from circadian rhythm sleep disorders (CRSD) like delayed sleep phase syndrome (DSPS), jet lag and shift-work sleep disorder. Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances of these patients. In comparison to a number of sleep-promoting compounds that are usually prescribed, such as benzodiazepines and z-drugs (zolpidem and zopiclon belonging to the latter ones), melatonin has several advantages of clinical value: it does not cause hangover nor withdrawal effects and is devoid of any addictive potential. However, recent meta-analyses revealed that melatonin is not sufficiently effective in treating most primary sleep disorders. Some of  the reasons for a limited efficacy of this natural hormone are related to its extremely short half-life in the circulation, and to the fact that sleep maintenance is also regulated by mechanisms downstream of primary melatonergic actions. Hence, there is an urgent need for the development of melatonin receptor agonists with a longer half-life, which could be suitable for a successful treatment of insomnia. Such requirements are fulfilled by ramelteon (CAS 196597-26-9), which possesses a high affinity for the melatonin receptors MT1 and MT2 present in the circadian pacemaker, the suprachiasmatic nucleus (SCN). Ramelteon also has a substantially longer half-life than melatonin. This new drug has been successfully used in treating elderly insomniacs without any adverse effects reported, and is promising for treating patients with primary insomnia and also those suffering from CRSD. Since sleep disturbances constitute the most prevalent symptoms of various forms of depression, t
he need for the development of an ideal antidepressant was felt, which would both improve sleep and mitigate depressive symptoms. Since most of the currently used antidepressants, including the selective serotonin re-uptake inhibitors worsen the sleep disturbances of depressive patients, another novel melatonergic drug, agomelatine (CAS 138112-76-2), holds some promise because of its particular combination of actions: it has a high affinity for MT1 and MT2 receptors in the SCN, but it acts additionally as a 5-HT(2C) antagonist [5-hydroxytryptamine (serotonin) receptor 2C antagonist]. The latter property, which is decisive for the antidepressive action, would not favor but potentially antagonize sleep, but this is overcome during night by the melatonergic, sleep-promoting effect. This drug has been found beneficial in treating patients with major depressive and seasonal affective disorders. Unlike the other antidepressants, agomelatine improves both sleep and clinical symptoms of depressive illness and does not have any of the side effects on sleep seen with other compounds in use. This property seems to be of particular value because of the aggravating effects of disturbed sleep in the development of depressive symptoms. Based on these facts, agomelatine seems to be a drug of superior efficacy with a promising future in the treatment of depressive disorders. However, long-term safety studies are required for both ramelteon and agomelatine, with a consideration of the pharmacology of their metabolites, their effects on redox metabolism, and of eventual undesired melatonergic effects, e. g., on reproductive functions. According to current data, both compounds seem to be safe during short-term treatment

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J Adv Nurs. 2008 Mar;61(6):664-75.
Efficacy of an insomnia intervention on fatigue, mood and quality of life in breast cancer survivors.
Dirksen SR, Epstein DR.
College of Nursing and Healthcare Innovation, Arizona State University, Phoenix, Arizona, USA. shannon.dirksen@asu.edu

AIM: This paper is a report of a study to describe the efficacy of cognitive behavioural therapy for insomnia on fatigue, mood and quality of life in breast cancer survivors. BACKGROUND: Women who receive primary treatment for breast cancer often complain of insomnia. Rarely evaluated in insomnia intervention studies is the effect of cognitive behavioural treatment on the psychosocial outcomes of fatigue, mood and quality of life. METHOD: Data were collected between December 2002 and March 2004 with 72 women who were at least 3 months post-completion of primary treatment without current evidence of disease. Women were randomly assigned to either the cognitive behavioural therapy for insomnia group, which received stimulus control instructions, sleep restriction therapy and sleep education and hygiene, or the component control group which received sleep education and hygiene only. The 10-week study consisted of 2 weeks of pre-treatment, 6 weeks of treatment and 2 weeks of post
-treatment. Fatigue, mood and quality of life were measured at pre- and post-treatment. FINDINGS: Women receiving cognitive behavioural therapy for insomnia had significant improvements in fatigue, trait anxiety, depression and quality of life. The component control group also had statistically significant increases in quality of life, with a trend suggestive of lower depression at post-treatment. CONCLUSION: Globally, as the number of survivors in this population continues to grow, it is imperative that nurses continue testing interventions that may positively affect quality of life and the commonly experienced symptoms of fatigue, anxiety and depression.

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J Intellect Disabil Res. 2008 Mar;52(Pt 3):256-64.
Melatonin treatment in individuals with intellectual disability and chronic insomnia: a randomized placebo-controlled study.
Braam W, Didden R, Smits M, Curfs L.
's Heeren Loo Zuid, Wekerom, The Netherlands. wiebe.braam@sheerenloo.nl

BACKGROUND: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. METHODS: The effectiveness of melatonin for the treatment of chronic sleep disturbance was assessed in a randomized double-blind placebo-controlled trial with 51 individuals with ID. All of these individuals presented with chronic ideopatic sleep disturbance for more than 1 year. The study consisted of a 1-week baseline, followed by 4 weeks of treatment. Parents or other caregivers recorded lights off time, sleep onset time, night waking, wake up time and epileptic seizures. Endogenous melatonin cycle was measured in saliva before and after treatment. RESULTS: Compared with placebo, melatonin significantly advanced mean sleep onset time by 34 min, decreased mean sleep latency by 29 min, increased mean total sleep time by 48 min, reduced the mean number of times the person awoke during the night by 0.4, decreased the mean duration of these night waking periods by 17 min and advanced endogenous melatonin onset at night by an average of 2.01 h. Lights off time, sleep offset time and the number of nights per week with night waking did not change. Only few minor or temporary adverse reactions and no changes in seizure frequency were reported. CONCLUSIONS: Melatonin treatment improves some aspects of chronic sleep disturbance in individuals with ID.

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J Am Acad Nurse Pract. 2008 Feb;20(2):69-75.
Sleeping through the night: Are extended-release formulations the answer?
Calamaro C.
College of Nursing and Health Professions, Drexel University, Philadelphia, Pennsylvania.

Purpose: To provide an overview of insomnia, including identification and current treatments, as well as review the efficacy and safety of extended-release sleep medication. Data sources: Published clinical research and review articles, DSM-IV criteria, and clinical trials. Conclusions: Insomnia is a highly prevalent and debilitating sleep disorder, which may present with one or more of the following symptoms: difficulty initiating sleep, difficulty maintaining sleep, or waking too early without being able to return to sleep. Difficulty maintaining sleep throughout the night is the most common symptom of insomnia. The recently approved nonbenzodiazepine hypnotic, zolpidem extended-release, can be taken as long as medically necessary to improve sleep-onset and reduce sleep-maintenance difficulties in insomnia patients, without negatively affecting next-day functioning. Implications for practice: Insomnia continues to be an underdiagnosed and undertreated disorder. The nurse practitioner, through routine inquiry about patient sleep habits and consideration of the appropriate treatment of insomnia, can help restore the quality of life of patients experiencing the negative consequences of insomnia.

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Clin Geriatr Med. 2008 Feb;24(1):107-19.
Nonpharmacologic therapy for insomnia in the elderly.
Joshi S.
Bettendorf Internal Medicine and Geriatrics, 4480 Utica Ridge Road, Suite 160, Bettendorf, IA 52722, USA.

Nonpharmacologic modalities may be used alone or in combination with pharmacologic therapy for effective treatment of insomnia in the elderly. Nondrug treatments involve behavioral, cognitive, and physiologic interventions. Common methods of cognitive behavior therapy for insomnia include: relaxation, stimulus control, sleep restriction, cognitive interventions or therapy, sleep education and sleep hygiene, light therapy, and chronotherapy. Evidence suggests that nonpharmacologic treatments are effective and well suited for the clinical management of insomnia in the elderly.

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Clin Geriatr Med. 2008 Feb;24(1):121-38.
Complementary and alternative medicine for sleep disturbances in older adults.
Gooneratne NS.
Division of Geriatric Medicine, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, 3615 Chestnut Street, Philadelphia, PA 19104, USA.

Complementary and alternative medicines (CAM) are frequently used for the treatment of sleep disorders, but in many cases patients do not discuss these therapies directly with their health care provider. There is a growing body of well-designed clinical trials using CAM that have shown the following: (1) Melatonin is an effective agent for the treatment of circadian phase disorders that affect sleep; however, the role of melatonin in the treatment of primary or secondary insomnia is less well established. (2) Valerian has shown a benefit in some, but not all clinical trials. (3) Several other modalities, such as Tai Chi, acupuncture, acupressure, yoga, and meditation have improved sleep parameters in a limited number of early trials. Future work examining CAM has the potential to significantly add to our treatment options for sleep disorders in older adults.

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Clin Geriatr Med. 2008 Feb;24(1):139-149.
Light Therapy for Insomnia in Older Adults.
Gammack JK.
Division of Geriatric Medicine, Saint Louis University Health Sciences Center, 1402 S. Grand Boulevard, M238, St. Louis, MO 63104, USA; Geriatric Research Education and Clinical Center (GRECC), Jefferson Barracks Veteran's Affairs Medical Center, 1 Jefferson Barracks Drive, St. Louis, MO 63125-4199, USA.

Exposure to bright light suppresses the production of melatonin and contributes to the regulation of the circadian rhythm. Because of environmental and medical conditions, older adults are less likely than younger adults to receive the prolonged, high intensity, daily bright light needed to promote a satisfactory sleep-wake cycle. The best available evidence for bright light therapy is in the management of seasonal affective disorder, which is relatively infrequent in the elderly population. For older adults with chronic insomnia, dementia, and nonseasonal depression, there is no consensus on the optimum treatment protocol for bright light therapy. However, in addition to sleep improvement, bright light therapy may be used to reduce unwanted behavioral and cognitive symptoms associated with dementia and depression in the elderly.

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Am J Geriatr Psychiatry. 2008 Jan;16(1):44-57.
Efficacy and Safety of Zolpidem Extended Release in Elderly Primary Insomnia Patients.
Walsh JK, Soubrane C, Roth T; on behalf of the ZOLELDERLY Study Group.
Sleep Medicine and Research Center, St. John’s Mercy and St. Luke’s Hospitals, St. Louis, MO (JKW); the Department of Psychology, Saint Louis University, St. Louis, MO (JKW); Clinical Development, Sanofi-Aventis Research, Chilly Mazarin, France (CS); and the Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI (TR).

Objectives: To evaluate the clinical efficacy and safety of zolpidem extended release for the treatment of primary insomnia in elderly patients. Methods: A randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 205 (117 women, 88 men; mean age 70.2 +/- 4.5 years) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined primary insomnia patients were randomized to 3 weeks of nightly treatment with either zolpidem extended release 6.25 mg or placebo; 198 patients completed the study. Results: Relative to placebo, zolpidem extended release 6.25 mg significantly decreased wake time after sleep onset during the first six hours of the night, as measured by polysomnogram (PSG). PSG latency to persistent sleep was reduced and PSG total sleep time was increased, both at nights 1/2 and 15/16. Patient self-report measures were significantly better with zolpidem extended-release 6.25 mg than with placebo throughout treatment. Some PSG measures indicated a worsening of sleep for a single night after abrupt discontinuation of zolpidem extended release. No next-morning residual effects were observed. The overall incidence and nature of adverse events was comparable between the two groups. Conclusions: Zolpidem extended release 6.25 mg improved both sleep maintenance and sleep induction in elderly primary insomnia patients during three weeks of administration.

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J Sleep Res. 2007 Dec;16(4):372-80.
Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects.
Lemoine P, Nir T, Laudon M, Zisapel N.
The Clinique Lyon-Lumière, Meyzieu, France.

Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR-melatonin) versus placebo treatment were assessed in a multi-center randomized placebo-controlled study in 170 primary insomnia outpatients aged > or =55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR-melatonin significantly improved QOS (-22.5 versus -16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW (-15.7 versus -6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side-effects were judged to be of minor severity. PR-melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation.

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Am J Manag Care. 2007 Nov;13(5 Suppl):S117-20.
The state of insomnia and emerging trends.
Roth T, Franklin M, Bramley TJ.
Xcenda, 1528 Preston St, Salt Lake City, UT 84108, USA.

Recent research into the pathophysiology of insomnia has brought a shift in the approach to treatment. Insomnia rarely occurs in isolation and is typically comorbid with other conditions. Rather than simply treating the primary disorder, whereby symptoms of insomnia may go unaddressed, now there is a push to acknowledge the existence of chronic insomnia as a disorder that itself merits treatment. This recognition is due to the identification of pathophysiologic changes and associated morbidity, which can be substantial. Insomnia patients have increased risk for psychiatric disorders, especially depression, anxiety, decreased quality of life, increased healthcare utilization and costs, drug/alcohol abuse, decreased occupational performance, and increased falls/accidents. Current management patterns explore non-nightly or discontinuous hypnotic treatment - non-nightly flexible, non-nightly semiflexible, non-nightly fixed, and flexible timing - which deviates from past trends of continuous dosing with hypnotics. These trends reflect a change from considering insomnia a symptom to treating insomnia as a disorder.

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Clin Interv Aging. 2007;2(3):313-26.
Eszopiclone for late-life insomnia.
McCrae CS, Ross A, Stripling A, Dautovich ND.
Department of Clinical and Health Psychology, University of Florida, PO Box 1001 65, Gainesville, FL 32610-0165, USA. cmccrae@phhp.ufl.edu

Insomnia, the most common sleep disturbance in later life, affects 20%-50% of older adults. Eszopiclone, a short-acting nonbenzodiazepine hypnotic agent developed for the treatment of insomnia, has been available in Europe since 1992 and in the US since 2005. Although not yet evaluated for transient insomnia in older adults, eszopiclone has been shown to be safe and efficacious for short-term treatment (2 weeks) of chronic, primary insomnia in older adults (64-91 years). Clinical studies in younger adults (mean = 44 years) have shown eszopiclone can be used for 6-12 months without evidence of problems. Because the oldest participant in these longer-term trials was 69, it not known whether eszopiclone is effective for older adults [particularly the old old (75-84 years) and oldest old (85+)] when used over longer periods. This is unfortunate, because older individuals frequently suffer from chronic insomnia. Cognitive-behavioral therapy for insomnia, which effectively targets the behavioral factors that maintain chronic insomnia, represents an attractive treatment alternative or adjuvant to eszopiclone for older adults. To date, no studies have compared eszopiclone to other hypnotic medications or to nonpharmacological interventions, such as cognitive-behavioral therapy for insomnia, in older adults. All of the clinical trials reported herein were funded by Sepracor. This paper provides an overview of the literature on eszopiclone with special emphasis on its use for the treatment of late-life insomnia. Specific topics covered include pharmacology, pharmacodynamics, pharmacokinetics, clinical trial data, adverse events, drug interactions, tolerance/dependence, and economics/cost considerations for older adults.

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Sleep. 2007 Nov 1;30(11):1555-61.
Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia.
Roth T, Rogowski R, Hull S, Schwartz H, Koshorek G, Corser B, Seiden D, Lankford A.
Henri Ford Hospital, Detroit, MI 48202, USA. troth1@hfhs.org

STUDY OBJECTIVES: To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients. DESIGN: Adults (18-64 y) with chronic primary insomnia (DSM-IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of doxepin, and placebo in a crossover study. Treatment periods consisted of 2 polysomnographic assessment nights with a 5-day or 12-day drug-free interval between periods. Efficacy was assessed using polysomnography (PSG) and patient-reported measures. Safety analyses included measures of residual sedation and adverse events. MEASUREMENTS AND RESULTS: Sixty-seven patients were randomized. Wake time during sleep, the a priori defined primary endpoint, was statistically significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All three doses had statistically significant improvements versus placebo for PSG-defined wake after sleep onset, total sleep time, and overall sleep efficiency (SE). SE in the final third-of-the-night also demonstrated statistically significant improvement at all doses. The doxepin 6 mg dose significantly reduced subjective latency to sleep onset. All three doxepin doses had a safety profile comparable to placebo. There were no statistically significant differences in next-day residual sedation, and sleep architecture was generally clinically preserved. ConclusionS: In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia.

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Sleep. 2007 Nov 1;30(11):1445-59.
Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report.
Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T, Chesson AL Jr, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ, Zak R; Standards of Practice Committee of the American Academy of Sleep Medicine.
Mayo Sleep Disorders Center, Mayo Clinic, Rochester, MN, USA.

The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses "exogenous" circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the "endogenous" circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from "Option" to "Guideline," depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs (Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline).

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Sleep Med. 2007 Sep 5; [Epub ahead of print]
Efficacy and tolerability of indiplon in older adults with primary insomnia.
Walsh JK, Moscovitch A, Burke J, Farber R, Roth T.
Sleep Medicine and Research Center, St. John’s/St. Luke’s Hospitals, 232 S. Woods Mill Road, Chesterfield, St. Louis, MO 63017, USA; Department of Psychology, Saint Louis University, St. Louis, MO, USA.

OBJECTIVE: To evaluate the efficacy and safety of indiplon in elderly patients with primary insomnia. PATIENTS AND METHODS: Elderly patients, 65-80 years (N=358; 55% female; mean age, 71 years) who met the criteria for primary insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) for three months were randomized to two weeks of double-blind nightly treatment with 5mg or 10mg indiplon or placebo. Daily self-assessments by the patients included latency to sleep onset (LSO), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and sleep quality. Data were collected between July, 2002, and October, 2003, at 52 clinical research sites in North America. RESULTS: Treatment with indiplon was associated with significant reduction in LSO at Week 1 for the 5mg (34.6+/-1.8min) and 10mg doses (30.4+/-1.6min) relative to placebo (47.4+/-2.5min; p<0.0001 for both comparisons). During Week 2, LSO remained s
horter on both indiplon doses compared to placebo (5mg, p=0.016; and 10mg, p=0.0028). During both study weeks, treatment with indiplon was also associated with significant improvement, relative to placebo, in TST, NAW, WASO, and sleep quality. The frequency of adverse events was similar in the indiplon 5mg and placebo groups; somnolence, nausea, depression and decreased appetite were slightly more common in the indiplon 10mg group. CONCLUSION: In elderly patients with primary insomnia, indiplon 5mg and 10mg were efficacious in inducing and maintaining sleep and improving sleep quality during the two weeks of treatment. Indiplon 5mg was well-tolerated, with no serious adverse events and no significant changes in electrocardiogram (ECG) or routine clinical laboratory evaluations; the 10mg dose produced slightly greater efficacy as well as somewhat increased adverse events.

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Rehabilitation (Stuttg). 2007 Aug;46(4):220-7.
[Predictors of the effectiveness of psychological sleep management in cancer patients during inpatient rehabilitation.]
[Article in German]
Simeit R, Deck R, Conta-Marx B.
1Röpersbergklinik Ratzeburg.

Insomnia is a common phenomenon in cancer patients; nevertheless, there are only a few intervention results published covering this topic. In a former study we examined the effects of a psychological sleep management programme with two intervention groups (n=80, n=71) and one control group (n=78) and showed significant improvements over time, indicating that 50% to 80% of the intervention group participants benefited with moderate or large scale effects on several sleep variables. Now we reanalysed data to look for predictors for those patients who improved best. Almost no demographic, cancer-related or quality of life variables predicted treatment response and persons with greater sleep disturbances at the beginning do benefit the same as persons with less problems. Additionally, better acceptance of the chosen intervention form (cognitive-behavioural programme with autogenic training or with muscle relaxation technique) positively predicted good outcome. Explained variance associated with different outcome variables varied between 9% and 18%. Therefore training should be offered for all cancer patients with sleep problems, and they should have a choice between different relaxation techniques.

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Sleep. 2007 Aug 1;30(8):959-68.
Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations.
Walsh JK, Krystal AD, Amato DA, Rubens R, Caron J, Wessel TC, Schaefer K, Roach J, Wallenstein G, Roth T.
Sleep Medicine and Research Center, St. John's/St. Luke's Hospitals and the Department of Psychology, Saint Louis University, St. Louis, MO 63017, USA. jwalsh@stlo.mercy.net

STUDY OBJECTIVES: To evaluate 6 months' eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations. DESIGN: Randomized, double blind, controlled clinical trial. SETTING: 54 research sites in the U.S. PATIENTS: 830 primary insomnia patients who reported mean nightly total sleep time (TST) < or = 6.5 hours/night and/or mean nightly sleep latency (SL) >30 min. INTERVENTION: Eszopiclone 3 mg or matching placebo. MEASUREMENTS: Patient-reported sleep measures, Insomnia Severity Index, Medical Outcomes Study Short-Form Health Survey (SF-36), Work Limitations Questionnaire, and other assessments measured during baseline, treatment Months 1-6, and 2 weeks following discontinuation of treatment. RESULTS: Patient-reported sleep and daytime function were improved more with eszopiclone than with placebo at all months (P <0.001). Eszopiclone reduced Insomnia Severity Index scores to below clinically meaningful levels for 50% of patients (vs 19% with placebo; P <0.05) at Month 6. SF-36 domains of Physical Functioning, Vitality, and Social Functioning were improved with eszopiclone vs placebo for the Month 1-6 average (P < 0.05). Similarly, improvements were observed for all domains of the Work Limitations Questionnaire with eszopiclone vs placebo for the Month 1-6 average (P <0.05). CONCLUSIONS: This is the first placebo-controlled investigation to demonstrate that long-term nightly pharmacologic treatment of primary insomnia with any hypnotic enhanced quality of life, reduced work limitations, and reduced global insomnia severity, in addition to improving patient-reported sleep variables.

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J Altern Complement Med. 2007 Jul-Aug;13(6):669-76.
Auricular acupuncture treatment for insomnia: a systematic review.
Chen HY, Shi Y, Ng CS, Chan SM, Yung KK, Zhang QL.
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong., School of Chinese Medicine, University of Hong Kong, Hong Kong.

Objectives: To review trials on the efficacy and safety of auricular acupuncture (AA) treatment for insomnia and to identify the most commonly used auricular acupoints for treating insomnia in the studies via a frequency analysis. Data sources: The international electronic databases searched included: (1) AMED; (2) the Cochrane library; (3) CINAHL; (4) EMBASE; and (5) MEDLINE.((R)) Chinese electronic databases searched included: (1) VIP Information; (2) CBMdisc; and (3) CNKI. Study selection: Any randomized controlled trials using AA as an intervention without using any co-interventions for insomnia were included. Studies using AA versus no treatment, placebo, sham AA, or Western medicine were included. Data extraction: Two (2) independent reviewers were responsible for data extraction and assessment. The efficacy of AA was estimated by the relative risk (RR) using a meta-analysis. Results: Eight hundred and seventy eight (878) papers were searched. Six (6) trials (402 treated with AA among 673 participants) that met the inclusion criteria were retrieved. A meta-analysis showed that AA was chosen with a higher priority among the treatment subjects than among the controls (p < 0.05). The recovery and improvement rates produced by AA was significantly higher than those of diazepam (p < 0.05). The rate of success was higher when AA was used for enhancement of sleeping hours up to 6 hours in treatment subjects (p < 0.05). The efficacy of using Semen vaccariae ear seeds was better than that of the controls (p < 0.01); while magnetic pearls did not show statistical significance (p = 0.28). Six (6) commonly used auricular acupoints were Shenmen (100%), Heart (83.33%), Occiput (66.67%), Subcortex (50%), Brain and Kidney (each 33.33%, respectively). Conclusions: AA appears to be effective for treating insomnia. Because the trials were low quality, further clinical trials with higher design quality, longer duration of treatment, and longer follow-up should be conducted.

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Presse Med. 2007 Jul 27; [Epub ahead of print]
[Objective improvement of sleep disorders in the elderly by a health education program.]
[Article in French]
Gauriau C, Raffray T, Choudat D, Corman B, Léger D.
Successful Aging Database, Boulogne-Billancourt (92); Centre du Sommeil et de la Vigilance, Centre de référence Hypersomnies rares, Hôtel Dieu, Paris (75).

INTRODUCTION: The prevalence of sleep disorders increases with age and reaches 20 to 40% of those older than 60 years. We set up a health education program to help the elderly to improve their sleep. It includes a preliminary 9-day evaluation with a sleep diary and wrist actigraph, a day of group cognitive behavioral therapy, and a follow-up assessment, again with sleep diary and actigraph. METHODS: Of the 26 study participants (9 men and 17 women, mean age: 68+/-1 years), 14 had insomnia with night awakenings of 1 hour or longer or a sleep latency of 30 minutes or longer or both (group 1). The other 12 (group 2) also complained of insufficient sleep. RESULTS: In the weeks following cognitive behavioral therapy, group 1 improved their total sleep time by an average of 24 to 33minutes, with reduced night-time awakenings and sleep latency and no change in their time spent in bed. Those in group 2 also increased their total sleep time by 18 to 47 minutes, by spending more time in bed and maintaining a sleep efficiency close to 88%. CONCLUSION: This study showed that cognitive behavioral therapy coupled with individual sleep evaluation improves sleep duration in elderly people who complain of insufficient sleep. These beneficial effects were accompanied by positive assessments of both subjective sleep quality and morning energy.

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Psychopharmacology (Berl). 2007 Jul 27; [Epub ahead of print]
Short-term treatment with gaboxadol improves sleep maintenance and enhances slow wave sleep in adult patients with primary insomnia.
Lundahl J, Staner L, Staner C, Loft H, Deacon S.
Department of Neurology, H. Lundbeck A/S, International Clinical Research, Ottiliavej 7-9, 2500, Valby, Denmark, jol@lundbeck.com.

RATIONALE: Gaboxadol is a selective extrasynaptic GABA(A) agonist, previously in development for the treatment of insomniac patients. OBJECTIVE: To evaluate the acute efficacy and safety of gaboxadol in primary insomnia (PI). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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J Clin Sleep Med. 2007 Jun 15;3(4):374-9.
Efficacy and tolerability of indiplon in transient insomnia.
Rosenberg R, Roth T, Scharf MB, Lankford DA, Farber R.
Atlanta Sleep Institute, Atlanta, GA 30342, USA. russell.rosenberg@atlantasleep.com

OBJECTIVE: The efficacy of indiplon was evaluated by polysomnography (PSG) in an experimental model of transient insomnia consisting of the first night effect combined with a 2-hour phase advance. METHODS: Healthy volunteers age 21-64 years (N=593; 62% female; mean +/- SEM) years, 32 +/- 0.39) were randomized to double-blind treatment with a single nighttime dose of indiplon (10 mg or 20 mg) or placebo. PSG assessments included latency to persistent sleep (LPS, primary endpoint) and total sleep time (TST); self-report assessments included sleep quality (SQ); next day residual effects were evaluated by the Digit Symbol Substitution Test (DSST), Symbol Copying Test (SCT), and a Visual Analog Scale of sleepiness (VAS). RESULTS: LPS mean (+/- SEM) values were significantly reduced on indiplon 10 mg (21.2 +/- 1.5 minutes) and indiplon 20 mg (16.8 +/- 1.1 minutes) compared to placebo (33.1 +/- 2.5 minutes; p < 0.0001 for both comparisons to placebo). TST mean (+/- SEM) values were significantly increased on indiplon 10 mg (414.5 +/- 3.9 minutes) and indiplon 20 mg (423.5 +/- 3.1 minutes) compared to placebo (402.9 +/- 3.9 minutes; p <0.005 for the 10 mg dose; p < 0.0001 for the 20 mg dose). SQ was also significantly improved on both doses. There were no differences between indiplon and placebo on next day DSST, SCT, or VAS. CONCLUSIONS: Indiplon was effective in inducing sleep, increasing sleep duration, and improving overall sleep quality without next day residual effects in healthy volunteers in a model of transient insomnia.

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Rev Bras Psiquiatr. 2007 May 23; [Epub ahead of print]
[Nonpharmacologic treatment of chronic insomnia.]
[Article in Portuguese]
Passos GS, Tufik S, Santana MG, Poyares D, Mello MT.
Universidade Federal de São Paulo, São Paulo, SP, Brasil.

The purpose of this manuscript is to briefly describe the main modalities of non-pharmacological therapy and its utilization on the chronic insomnia treatment. Insomnia is the most frequent sleep disorder and that is more associated with psychiatry disorders. The pharmacotherapy is the most frequent treatment, but the nonpharmacologic therapy has been studied. The most common therapy modalities include behavioral approaches, stimulus control, sleep restriction, paradoxical intention, sleep hygiene, progressive muscle relaxation and biofeedback and, more recently, physical exercise practices. At first behavioral therapy aimed to improve sleep quality, however, recent studies have been emphasizing the effect of behavioral and cognitive approaches on quality of life, on decrease of dosage and frequency of drugs intake. Since insomnia is a chronic condition, long-term and safe treatments are warranted.

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J Clin Psychiatry. 2007;68 Suppl 5:13-8.
A physiologic basis for the evolution of pharmacotherapy for insomnia.
Roth T.
Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA. troth1@hfhs.org

Insomnia is a highly prevalent disorder with consequences for the patient's physical and mental health, daily function, and job performance. Although the exact pathophysiology of insomnia is unknown, recent research has demonstrated that normal sleep and wakefulness are controlled by reciprocal inhibition by different brain regions. This sleep-wake control system offers multiple therapeutic targets for the treatment of insomnia; currently, most research and available hypnotic agents target gamma-aminobutyric acid (GABA) on the sleep side of the switch. Historically, drugs have evolved from benzodiazepine receptor agonists to nonbenzodiazepines to, most recently, selective extrasynaptic GABA(A) receptor agonists. However, these drugs have a differential impact on characteristics of sleep. Among the compounds that modulate the benzodiazepine-sensitive GABA(A) receptors, benzodiazepines suppress stage 3-4 sleep, whereas nonbenzodiazepines have no substantial effect on these stages of sleep. Recently, work on GABA agonists indicates that they increase stage 3-4 sleep. This has been demonstrated via sleep-stage scoring as well as with spectral analysis. Further, this increase in stage 3-4 sleep is associated with a decrease in stage 1 sleep and arousals from sleep. Thus, the GABA agonists may not simply promote sleep, but consolidate it as well. The clinical utility of the increase in slow-wave sleep and the sleep consolidation it produces warrants further investigation.

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Phytother Res. 2007 May 8; [Epub ahead of print]
A randomized, double blind, placebo-controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian hops extract combination (Ze 91019) in patients suffering from non-organic sleep disorder.
Koetter U, Schrader E, Kaufeler R, Brattstrom A.
Max Zeller Sohne AG, CH-8590 Romanshorn, Switzerland.

Valerian and hops are traditionally used as sleep aids. Since the fixed extract combination (Ze 91019) as a whole is considered the active compound, the clinical efficacy must be demonstrated for this extract combination. The present clinical study aimed to demonstrate superiority of the fixed extract combination in comparison with placebo in patients suffering from non-organic insomnia (ICD 10, F 51.0-51.2). Objective sleep parameters were registered by means of a transportable home recorder system (QUISI). The primary outcome was the reduction in sleep latency (SL2) which had to be prolonged at baseline (>/=30 min) as an inclusion criteria. The treatment period lasted for 4 weeks with either placebo, single valerian extract (Ze 911) or the fixed valerian hops extract combination (Ze 91019). The amount of the single valerian extract was identical to that amount contained in the fixed extract combination, i.e. 500 mg valerian extract siccum. In the extract combination 120 mg hops extract siccum was added. Both the extracts were prepared with 45% methanol m/m with a drug-extract ratio of 5.3:1 (valerian) and 6.6:1 (hops), respectively. The fixed extract combination was significantly superior to the placebo in reducing the sleep latency whilst the single valerian extract failed to be superior to the placebo. The result underlined the plausibility for adding hops extract to the valerian extract. Copyright (c) 2007 John Wiley & Sons, Ltd.

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CMAJ. 2007 May 8;176(10):1449-54.
Sleep and aging: 2. Management of sleep disorders in older people.
Wolkove N, Elkholy O, Baltzan M, Palayew M.
Sleep Clinic, Mount Sinai Hospital Center, Montreal, Que. norluco@yahoo.com

The treatment of sleep-related illness in older patients must be undertaken with an appreciation of the physiologic changes associated with aging. Insomnia is common among older people. When it occurs secondary to another medical condition, treatment of the underlying disorder is imperative. Benzodiazepines, although potentially effective, must be used with care and in conservative doses. Daytime sedation, a common side effect, may limit use of benzodiazepines. Newer non-benzodiazepine drugs appear to be promising. Rapid eye movement (REM) sleep behaviour disorder can be treated with clonazepam, levodopa-carbidopa or newer dopaminergic agents such as pramipexole. Sleep hygiene is important to patients with narcolepsy. Excessive daytime sleepiness can be treated with central stimulants; cataplexy may be improved with an antidepressant. Restless legs syndrome and periodic leg-movement disorder are treated with benzodiazepines or dopaminergic agents such as levodopa-carbidopa and, more recently, newer dopamine agonists. Treatment of obstructive sleep apnea includes weight reduction and proper sleep positioning (on one's side), but may frequently necessitate the use of a continuous positive air-pressure (CPAP) device. When used regularly, CPAP machines are very effective in reducing daytime fatigue and the sequelae of untreated obstructive sleep apnea.

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J Consult Clin Psychol. 2007 Apr;75(2):325-35.
Hypnotic taper with or without self-help treatment of insomnia: a randomized clinical trial.
Belleville G, Guay C, Guay B, Morin CM.
Departement de Psychologie, Universite du Quebec a Montreal, Montreal, Quebec, Canada.

This study aimed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment (CBT) for insomnia. Fifty-three adult chronic users of hypnotics were randomly assigned to an 8-week hypnotic taper program, used alone or combined with a self-help CBT. Weekly hypnotic use decreased in both conditions, from a nearly nightly use at baseline to less than once a week at posttreatment. Nightly dosage (in lorazepam equivalent) decreased from 1.67 mg to 0.12 mg. Participants who received CBT improved their sleep efficiency by 8%, whereas those who did not remained stable. Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone. Total sleep time remained stable throughout withdrawal in both CBT and taper conditions. The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication. The addition of a self-help treatment focusing on insomnia, a readily available and cost-effective alternative to individual psychotherapy, produced greater sleep improvement. Copyright 2007 APA, all rights reserved.

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Nat Clin Pract Neurol. 2007 Apr;3(4):221-8.
Drug Insight: the use of melatonergic agonists for the treatment of insomnia-focus on ramelteon.
Pandi-Perumal SR, Srinivasan V, Poeggeler B, Hardeland R, Cardinali DP.
Comprehensive Center for Sleep Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. pandiperumal@gmail.com

Melatonin, a chronobiotic that participates in the control of the circadian system, is known for its sleep-promoting effects, which include shortening of sleep latency and lengthening of sleep duration. As a result of its short half-life, melatonin does not exhibit undesirable side effects, and its broad applicability for a variety of sleep problems has been the focus of numerous scientific studies. Melatonin has not, however, received regulatory approval from the US FDA as a drug, because it can be sold freely as a food supplement. Consequently, there has been an active search for patentable melatonin receptor ligands in recent years. Ramelteon, an agonist that acts solely on melatonin MT(1) and MT(2) receptors, is of particular interest, and preliminary research indicates that it holds considerable promise for clinical applications. Ramelteon has been shown to induce sleep initiation and maintenance in various animal models and in clinical trials. In chronic insomnia, ramelteon decreases sleep latency and increases total sleep time and sleep efficiency, without causing hangover, addiction or withdrawal effects. Ramelteon is thought to promote sleep by influencing homeostatic sleep signaling mediated by the suprachiasmatic nucleus. Although ramelteon's metabolism and pharmacokinetics differ from those of melatonin, its safety seems to be sufficient for short-term application. Its long-term effects remain to be determined.

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Clin Drug Investig. 2007;27(5):325-32.
Role of lormetazepam in the treatment of insomnia in the elderly.
De Vanna M, Rubiera M, Luisa Onor M, Aguglia E.
Department of Clinical Psychiatry, Faculty of Medicine, University of Trieste, Trieste, Italy.

BACKGROUND and objective: Sleep architecture changes with age, both in terms of efficiency and total duration of sleep. Hypnotic benzodiazepines promote rapid onset of sleep, uninterrupted sleep and longer duration of sleep in the absence of carryover sedation the following morning; therefore, these may be appropriate for use in older patients. This study was performed to evaluate the efficacy and safety of lormetazepam in elderly patients with primary insomnia when used in association with sleep hygiene training (SHT). The impact of restored sleep on daily sleepiness was also investigated. PATIENTS AND METHODS: In this open-label study, 30 elderly outpatients with insomnia were randomised to receive 2 weeks of treatment with lormetazepam 0.5mg + SHT or SHT alone, followed by a 1-week observation period. Details on sleep latency, number of awakenings and freshness on awakening were recorded by patients in a daily sleep diary. The Epworth Sleepiness Scale (ESS) and Stanford Sleepiness Scale (SSS) were used to measure daily sleepiness. RESULTS: Addition of lormetazepam to SHT improved all sleep parameters measured compared with SHT alone. Mean duration of sleep improved significantly from baseline (mean rank = 1.00) in the lormetazepam + SHT group after 2 weeks of treatment (mean rank 2.87; Friedmann test = 27.448; p < 0.001), but declined significantly in the group receiving SHT alone (from mean rank 2.33 to 1.57; Friedmann test = 6.465; p < 0.05). Mean duration of sleep increased by approximately 150 minutes each night in the lormetazepam + SHT group but decreased by more than 30 minutes in the SHT-only group. Improvement in sleep quality from baseline was statistically significant only in the lormetazepam + SHT group: for both deepness of sleep and the perception of awakening refreshed, mean scores increased from approximately 3 at baseline to approximately 8 (on a scale of 1-10) after 2 weeks in this group. Sleep latency also decreased significantly in the lormetazepam + SHT group: after 2 weeks, on average patients were awakening less than once per night. SSS and ESS scores also improved significantly in the lormetazepam + SHT group; in contrast, in the SHT-only group, the mean ESS score worsened significantly from baseline and the mean SSS score remained relatively constant. No rebound insomnia was reported during follow-up in patients in the lormetazepam group. Vital signs did not change from baseline and no adverse events were reported for either group. CONCLUSION: Management of insomnia in the elderly appears to have a better outcome when pharmacotherapy is combined with SHT rather than SHT alone. The earlier improvement in sleep quality with lormetazepam when used in combination with a sleep training programme may help to maintain adherence to treatment.

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CNS Drugs. 2007;21(5):389-405.
Use of non-benzodiazepine hypnotics in the elderly : are all agents the same?
Dolder C, Nelson M, McKinsey J.
Wingate University School of Pharmacy, Wingate, North Carolina, USANorthEast Medical Center, Concord, North Carolina, USA.

Sleep disorders, especially insomnia, are common in older adults. These disorders are frequently treated using non-benzodiazepine hypnotics. Nonetheless, there is a relative lack of data regarding the use of these agents in the elderly, and whether any of these medications is superior to any other in the class when used in the elderly is also unclear.In this article, we review, by way of the published literature, the pharmacodynamics, pharmacokinetics, drug interactions, efficacy and safety of zolpidem, zaleplon, zopiclone, eszopiclone and ramelteon in the elderly. Special emphasis is placed on identifying relevant differences between these medications when used in older adults with insomnia. Based primarily on data from placebo-controlled trials, the non-benzodiazepines reviewed were found to be most effective at improving sleep latency and sleep quality, and least effective at enhancing total sleep time. The efficacy of ramelteon was limited to improving sleep latency, while all other agents, especially at higher doses, were found to produce improvement in both sleep latency and some improvement in total sleep time. All of the medications were found to be well tolerated in the elderly. From pharmacokinetic and drug-drug interaction perspectives, zaleplon and ramelteon offer the advantage of not being primarily metabolised via the cytochrome P450 3A4 isoenzyme.In conclusion, based on relatively limited data, zopiclone, zolpidem, zaleplon, eszopiclone and ramelteon represent modestly effective and generally well tolerated treatments for insomnia in older adults. While some actual and potential differences exist among these medications, more comparative trials are needed.

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Sleep. 2007 Mar 1;30(3):281-7.
Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia.
Deacon S, Staner L, Staner C, Legters A, Loft H, Lundahl J.
H. Lundbeck A/S, International Clinical Research, Valby, Denmark. stde@lundbeck.com

STUDY OBJECTIVE: To perform an early evaluation of the efficacy and safety of gaboxadol in the treatment of primary insomnia. METHODS: 26 adults (18-65 years) with DSM-IV criteria for primary insomnia were randomly assigned gaboxadol (5 mg, 15 mg) or placebo in a double-blind, crossover study. After a 3-night polysomnographic (PSG) screen, treatment was administered 30 min before bedtime on 2 consecutive nights during 3 separate sessions including PSG. Efficacy analyses (n = 23) were based on the average of Nights 1 and 2, and compared gaboxadol versus placebo. Baseline was the average of Nights 2 and 3 of the screening session. Both gaboxadol doses significantly (P < 0.05) improved mean total sleep time (mean +/- SD: baseline = 368.0 +/- 51.1 min, 15 mg = 420.3 +/- 24.5 min, 5 mg = 419.8 +/- 20.4 min, placebo = 408.7 +/- 30.4 min). Both gaboxadol doses reduced mean wake after sleep onset, although statistical significance was only achieved with 5 mg (baseline = 61.6 +/- 35.4 min, 15 mg = 38.0 +/- 21.1 min, 5 mg = 34.6 +/- 14.3 min, placebo = 43.4 +/- 22.9 min). Gaboxadol 15 mg also significantly reduced mean latency to persistent sleep (baseline = 55.6 +/- 27.0 min, 15 mg = 23.6 +/- 15.1 min, placebo = 30.0 +/- 19.1 min) and enhanced slow wave duration (baseline = 72.4 +/- 20.8 min, 15 mg = 114.0 +/- 37.5 min, placebo = 93.9 +/- 31.3 min) with no significant effects on REM sleep duration. Patient reports (Leeds Sleep Evaluation Questionnaire) of reduced time to sleep and increased sleep quality showed significant improvement with gaboxadol 15 mg. No next-day residual effects were observed with either dose of gaboxadol (assessed 2 h and 9 h after lights on). All adverse events were mild or moderate. CONCLUSION: Gaboxadol 15 mg was effective and generally well tolerated in the short-term treatment of patients with primary insomnia. Gaboxadol also enhanced slow wave sleep duration and had no significant effects on REM sleep duration. These findings suggest that gaboxadol may be a useful treatment for insomnia.

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MedGenMed. 2007 Jan 17;9(1):11.
Insomnia: zolpidem extended-release for the treatment of sleep induction and sleep maintenance symptoms.
Doghramji PP.
Collegeville Family Practice, Collegeville, Pennsylvania, USA. HyeDoc@pol.net

Insomnia impairs daytime functioning or causes clinically significant daytime distress. The consequences of insomnia, if left untreated, may contribute to the risks of developing additional serious conditions, such as psychiatric illness, cardiovascular disease, or metabolic issues. Furthermore, some comorbidities associated with insomnia may be bidirectional in their causality because psychiatric and other medical problems can increase the risk for insomnia. Regardless of the serious consequences of inadequately treated insomnia, clinicians often do not inquire into their patients' sleep habits, and patients, in turn, are not forthcoming with details of their sleep difficulties. The continuing education of physicians and patients with regard to insomnia and currently available therapies for the treatment of insomnia is, therefore, essential. Insomnia may present as either a difficulty falling asleep, difficulty maintaining sleep, or waking too early without being able to return to sleep. Furthermore, these symptoms often change over time in an unpredictable manner. Therefore, when considering a sleep medication, one with efficacy for the treatment of multiple insomnia symptoms is recommended. A modified-release formulation of zolpidem, zolpidem extended-release, has been approved for the treatment of insomnia characterized by both difficulty in falling asleep and maintaining sleep. Here, we review studies supporting the use of zolpidem extended-release in the treatment of sleep-onset and sleep maintenance difficulties.

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Psychiatr Prax. 2007 Jan;34(1 Suppl):95-7.
[Sedative antidepressants in the treatment of primary insomnia.]
[Article in German]
Lange K, Geisler P, Klein HE, Hajak G.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie der Universitat Regensburg.

OBJECTIVE There is a trend towards using sedative antidepressants in the treatment of insomnia. Efficacy, safety and clinical evidence for the use of antidepressants in the treatment of insomnia was evaluated according to published literature. METHODS A Medline literature search was conducted including the years 1975 - 2005. The key words primary insomnia, antidepressant treatment, Doxepin, Trimipramine, Trazodone, Mirtazapine and Nefazodone were used to identify relevant publications. RESULTS Evidence from few randomised, double-blind, placebo controlled studies for efficacy in primary insomnia is given for few substances such as Trimipamine, Doxepin, Mirtazapine and Trazodone. Side effects widely varied between drugs. CONCLUSIONS Few antidepressants appear to improve initiating and maintaining sleep in insomniacs. The safety profile is not studied sufficiently. Varying quality of studies, low number of investigated subjects, high incidence of unwanted side effects, and lack of confirmatory studies challenge the clinical value of antidepressants in insomnia treatment.

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Pharmacotherapy. 2007 Jan;27(1):89-110.
Therapeutic options for sleep-maintenance and sleep-onset insomnia.
Morin AK, Jarvis CI, Lynch AM.
1 Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Worcester, Massachusetts.

Insomnia, defined as difficulty falling asleep, staying asleep, and/or experiencing restorative sleep with associated impairment or significant distress, is a common condition resulting in significant clinical and economic consequences. Many options are available to treat insomnia, to assist with either falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for articles published between January 1996 and January 2006, evaluated abstracts from recent professional meetings, and contacted the manufacturer of the most recent addition to the pharmacologic armamentarium for insomnia treatment (ramelteon) to gather information. Nonpharmacologic options include stimulus control, sleep hygiene education, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription and over-the-counter drug therapies include benzodiazepine and nonbenzodiazepine sedative-hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and sedating antihistamines. Herbal and alternative preparations include melatonin and valerian. Before recommending any treatment, clinicians should consider patient-specific criteria such as age, medical history, and other drug use, as well as the underlying cause of the sleep disturbance. All pharmacotherapy should be used with appropriate caution, at minimum effective doses, and for minimum duration of time.

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Sleep. 2006 Dec 1;29(12):1573-85.
Effects of atomoxetine and methylphenidate on sleep in children with ADHD.
Sangal RB, Owens J, Allen AJ, Sutton V, Schuh K, Kelsey D.
Clinical Neurophysiology Services, PC, Troy, MI, USA.

STUDY OBJECTIVES: This study compared the effects of atomoxetine and methylphenidate on the sleep of children with attention-deficit/hyperactivity disorder (ADHD). This study also compared the efficacy of these medications for treating ADHD in these children. DESIGN: Randomized, double-blind, crossover trial. SETTING: Two sleep disorders centers in the United States; 1 in a private-practice setting and 1 in a hospital setting. PATIENTS: 85 children diagnosed with ADHD. INTERVENTIONS: Twice-daily atomoxetine and thrice-daily methylphenidate, each for approximately 7 weeks. MEASUREMENTS AND RESULTS: Relative to baseline, the actigraphy data indicated that methylphenidate increased sleep-onset latency significantly more than did atomoxetine (39.2 vs 12.1 minutes, p < .001). These results were consistent with the polysomnography data. Child diaries indicated that it was easier to get up in the morning, it took less time to fall asleep, and the children slept better with atomoxetine, compared with methylphenidate. Parents reported that it was less difficult getting their children up and getting them ready in the morning and that the children were less irritable, had less difficulty getting ready for bed, and had less difficulty falling asleep with atomoxetine, compared with methylphenidate. There were no significant differences between medications using the main measures of efficacy for ADHD treatment. Atomoxetine was superior on some secondary ADHD treatment-efficacy measures, based on parent reports. The only significant differences in treatment-emergent adverse events were greater incidence of decreased appetite and greater incidence of insomnia with methylphenidate. CONCLUSIONS: Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies, relative to thrice-daily methylphenidate, based on objective actigraphy and polysomnography data. Although both medications decreased nighttime awakenings, the decrease was greater for methylphenidate.

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South Med J. 2006 Dec;99(12):1373-7.
Pharmacologic management of chronic insomnia.
Taylor JR, Vazquez CM, Campbell KM.
Department of Pharmacy Practice, University of Florida College of Pharmacy, PO Box 100486, Gainesville, FL 32610-0486, USA. jtaylor@cop.ufl.edu

Chronic insomnia is a common disorder that is under recognized, under diagnosed and under treated. Initial assessment should focus on identifying and treating, if present, any secondary causes of insomnia. Primary insomnia can be treated with behavioral and/or pharmacological therapy. A thorough sleep history can identify the type of insomnia present, its severity, and can consequently guide therapy. Behavioral therapy has been shown to be equivalent to or superior to pharmacologic therapy, at least in some patients. It is a reasonable initial approach, although there are barriers to its use. There are several pharmacologic agents available, some of which are more effective at reducing time to fall asleep and others for maintaining sleep. There is some evidence to indicate that combining the approaches may impair outcomes. There is little data on the long-term use of pharmacologic agents.

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Drugs. 2006;66(18):2357-70.
Shift work sleep disorder: burden of illness and approaches to management.
Schwartz JR, Roth T.
Integris Sleep Disorder Center and University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73109, USA.

More than 6 million Americans work night shifts on a regular or rotating basis. The negative consequences of shift work have been established, and recent evidence suggests that patients with shift work sleep disorder (SWSD) are at increased risk of these consequences and co-morbidities. SWSD is a relatively common but under-recognised, and hence undertreated, condition with potentially serious medical, social, economic and quality-of-life consequences. In addition to increased risk of gastrointestinal and cardiovascular disease, patients with SWSD experience clinically significant excessive sleepiness or insomnia associated with work during normal sleep times, which has important safety implications. A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amfetamine), and the wake-promoting agents modafinil and armodafinil. However, most studies evaluating pharmacological therapies and nonpharmacological interventions simulate night-shift work under conditions that may not accurately reflect real-world activities. Pharmacological and nonpharmacological countermeasures evaluated mostly in simulated laboratory conditions have been shown to improve alertness or sleep in shift workers but have not yet been evaluated in patients with SWSD. To date, three randomised, double-blind clinical studies have evaluated pharmacological therapies in patients with SWSD. These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. In conclusion, SWSD is a common condition that remains under-recognised and undertreated. Further research is needed to evaluate different treatment approaches for this condition, to clarify the substantial health and economic consequences of SWSD, and to determine the potential for interventions or treatments to reduce the negative consequences of this condition.

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J Ky Med Assoc. 2006 Nov;104(11):502-12.
New solutions for treating chronic insomnia: an introduction to behavioral sleep medicine.
Wetzler RG, Winslow DH.
Behavioral Sleep Medicine Clinic, Sleep Medicine Specialists, Louisville, KY 40217, USA. rwetzler@kysleepmed.com

Insomnia is one of the most frequent complaints brought to primary care physicians and research suggests insomnia's prevalence is on the rise. Insomnia evaluation and treatment can be a time-intensive process that puts significant demands on a busy medical practice. To date, hypnotic medications are the most frequently prescribed treatment for insomnia and have been demonstrated to be efficacious for the treatment of acute insomnia. Cognitive-behavioral treatment (CBT) has been found to be just as effective as hypnotics for the treatment of acute insomnia and more effective for the treatment of chronic insomnia. CBT is now recognized as a first-line intervention for chronic insomnia, yet is underutilized. Many patients and healthcare providers are unaware of the efficacy of CBT for insomnia and currently there are few qualified providers. To address this need, the American Academy of Sleep Medicine (AASM) has developed a new subspeciality to train providers in the provision of CBT for insomnia as well as other sleep disorders.
 

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