日本神経治療学会治療指針作成委員会：日本神経治療学会 標準的神経治療 不眠・過眠と概日リズム障害、2016.
Yoshitaka Kaneita, Takashi Ohida, Makoto Uchiyama, Shinji Takemura, Kazuo Kawahara, Eise Yokoyama, Takeo Miyake, Satoru Harano, Kenshu Suzuki, Yuko Yagi, Akiyo Kaneko, Takako Tsutsui, Tsuneto Akashiba
Excessive daytime sleepiness among the Japanese general population.
J Epidemiol. 2005 Jan;15(1):1-8.
Abstract/Text
BACKGROUND: Excessive daytime sleepiness is one of the principal symptoms of sleep disturbances, and is often associated with serious consequences including traffic and industrial accidents, decreased productivity, and interpersonal problems. However, there are few epidemiologic studies on excessive daytime sleepiness in a large scale sample targeting Japanese general population.
METHODS: The survey was performed using a self-administered questionnaire in June 2000, targeting a population randomly selected from among 300 communities throughout Japan. This questionnaire included information about sleep habits and sleep problems. Excessive daytime sleepiness measured according to a question "Do you fall asleep when you must not sleep (for example when you are driving a car)?"
RESULTS: A total of 28,714 subjects completed the questionnaire. The prevalence of excessive daytime sleepiness was 2.5% (male=2.8% and female=2.2%). Backward elimination analysis showed that the following were associated with excessive daytime sleepiness: male sex, young age, short sleep duration, subjective insufficient sleep, loss of deep sleep, disagreeable sensations in the legs, interruption of sleep by snoring or dyspnea, and feeling psychological stress. Interruption of sleep by snoring or dyspnea was the strongest associated factor (adjusted odds ratio=2.46, 95% confidence interval=1.76-3.43) of excessive daytime sleepiness.
CONCLUSIONS: These results suggest that excessive daytime sleepiness in Japanese is associated with several sleep problems. These findings may be useful in attempts to prevent excessive daytime sleepiness in the general population of Japan.
Yoko Komada, Yuichi Inoue, Kenichi Hayashida, Toru Nakajima, Makoto Honda, Kiyohisa Takahashi
Clinical significance and correlates of behaviorally induced insufficient sleep syndrome.
Sleep Med. 2008 Dec;9(8):851-6. doi: 10.1016/j.sleep.2007.08.018. Epub 2007 Nov 5.
Abstract/Text
BACKGROUND AND PURPOSE: The aim of this study was to investigate the demographic variables and clinical characteristics of behaviorally induced insufficient sleep syndrome (BIISS) and to compare it with the other major hypersomnia disorders.
PATIENTS AND METHODS: One-thousand two-hundred forty-three consecutive patients referred to the outpatient clinic for complaint of excessive daytime sleepiness (EDS) were retrospectively investigated.
RESULTS: The rate of BIISS in patients with EDS was 7.1%, predominant in males. The mean age of initial visit was younger than that for obstructive sleep apnea syndrome (OSAS), while the mean age of onset of symptoms was older than that for idiopathic hypersomnia, narcolepsy, and circadian rhythm sleep disorders. The mean Epworth sleepiness scale (ESS) score before treatment was lower than that for narcolepsy but higher than that for both OSAS and circadian rhythm sleep disorders. Twenty-two percent of BIISS cases reported having accidents or near-miss accidents during the five-year period preceding the investigation, and this group showed higher ESS scores than the group without accidents.
CONCLUSIONS: Our findings showed that an unignorably large number of people suffer from BIISS, and that people with severe cases of the disorder are at high risk for getting into an accident. Characteristics and demographic information could be helpful for making a differential diagnosis of BIISS.
Marcia E. Hypersomnia in Older Patients. Sleep Med Clin 2012;7:365-378.
A T Mulgrew, G Nasvadi, A Butt, R Cheema, N Fox, J A Fleetham, C F Ryan, P Cooper, N T Ayas
Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea.
Thorax. 2008 Jun;63(6):536-41. doi: 10.1136/thx.2007.085464. Epub 2008 Jan 30.
Abstract/Text
BACKGROUND: Obstructive sleep apnoea/hypopnoea (OSAH) appears to be associated with an increased risk of motor vehicle crashes (MVCs). However, its impact on crash patterns, particularly the severity of crashes, has not been well described. A study was undertaken to determine whether OSAH severity influenced crash severity in patients referred for investigation of suspected sleep-disordered breathing.
METHODS: Objective crash data (including the nature of crashes) for 783 patients with suspected OSAH for the 3 years prior to polysomnography were obtained from provincial insurance records and compared with data for 783 age- and sex-matched controls. The patient group was 71% male with a mean age of 50 years, a mean apnoea-hypopnoea index (AHI) of 22 events/h and a mean Epworth Sleepiness Scale score of 10.
RESULTS: There were 375 crashes in the 3-year period, 252 in patients and 123 in controls. Compared with controls, patients with mild, moderate and severe OSAH had an increased rate of MVCs with relative risks of 2.6 (95% CI 1.7 to 3.9), 1.9 (95% CI 1.2 to 2.8) and 2.0 (95% CI 1.4 to 3.0), respectively. Patients with suspected OSAH and normal polysomnography (AHI 0-5) did not have an increased rate of MVC (relative risk 1.5 (95% CI 0.9 to 2.5), p = 0.21). When the impact of OSAH on MVC associated with personal injury was examined, patients with mild, moderate and severe OSAH had a substantially higher rate of MVCs than controls with relative risks of 4.8 (95% CI 1.8 to 12.4), 3.0 (95% CI 1.3 to 7.0) and 4.3 (95% CI 1.8 to 8.9), respectively, whereas patients without OSAH had similar crash rates to controls with a relative risk of 0.6 (95% CI 0.2 to 2.5). Very severe MVCs (head-on collisions or those involving pedestrians or cyclists) were rare, but 80% of these occurred in patients with OSAH (p = 0.06).
CONCLUSION: Patients with OSAH have increased rates of MVCs, and disproportionately increased rates of MVCs are associated with personal injury.
J F Pagel
Excessive daytime sleepiness.
Am Fam Physician. 2009 Mar 1;79(5):391-6.
Abstract/Text
Excessive daytime sleepiness is one of the most common sleep-related patient symptoms, and it affects an estimated 20 percent of the population. Persons with excessive daytime sleepiness are at risk of motor vehicle and work-related incidents, and have poorer health than comparable adults. The most common causes of excessive daytime sleepiness are sleep deprivation, obstructive sleep apnea, and sedating medications. Other potential causes of excessive daytime sleepiness include certain medical and psychiatric conditions and sleep disorders, such as narcolepsy. Obstructive sleep apnea is a particularly significant cause of excessive daytime sleepiness. An estimated 26 to 32 percent of adults are at risk of or have obstructive sleep apnea, and the prevalence is expected to increase. The evaluation and management of excessive daytime sleepiness is based on the identification and treatment of underlying conditions (particularly obstructive sleep apnea), and the appropriate use of activating medications.
K K Li, C Kushida, N B Powell, R W Riley, C Guilleminault
Obstructive sleep apnea syndrome: a comparison between Far-East Asian and white men.
Laryngoscope. 2000 Oct;110(10 Pt 1):1689-93. doi: 10.1097/00005537-200010000-00022.
Abstract/Text
OBJECTIVES: To investigate the possible differences between Far-East Asian men and white men in obstructive sleep apnea syndrome (OSAS).
STUDY DESIGN: Prospective nonrandomized controlled study.
METHODS: This study compared consecutive Far-East Asian men with OSAS (n = 50) with two selected groups of White men with OSAS (n = 50 in each group). One group of white men was controlled for age, respiratory disturbance index (RDI), and minimum oxygenation saturation (LSAT). Another group was controlled for age and body mass index (BMI). Cephalometric analysis was performed on all subjects.
RESULTS: The majority of the Far-East Asian men were found to be nonobese (mean BMI, 26.7 +/- 3.8) but had severe OSAS (mean RDI, 55.1 +/- 35.1). When controlled for age, RDI, and LSAT, the white men were substantially more obese (mean BMI, 29.7 +/- 5.8, P = .0055). When controlled for age and BMI, the white men had less severe illness (RDI, 34.1 +/- 17.9, P = .0001). Although the posterior airway space and the distance from the mandibular plane to hyoid bone were less abnormal in the Far-East Asian men, the cranial base dimensions were significantly decreased.
CONCLUSIONS: The majority of the Far-East Asian men in this study were found to be nonobese, despite the presence of severe OSAS. When compared with white men, Far-East Asian men were less obese but had greater severity of OSAS. There may be differences in obesity and craniofacial anatomy as risk factors in these two groups.
Terry Young, James Skatrud, Paul E Peppard
Risk factors for obstructive sleep apnea in adults.
JAMA. 2004 Apr 28;291(16):2013-6. doi: 10.1001/jama.291.16.2013.
Abstract/Text
P E Peppard, T Young, M Palta, J Dempsey, J Skatrud
Longitudinal study of moderate weight change and sleep-disordered breathing.
JAMA. 2000 Dec 20;284(23):3015-21.
Abstract/Text
CONTEXT: Excess body weight is positively associated with sleep-disordered breathing (SDB), a prevalent condition in the US general population. No large study has been conducted of the longitudinal association between SDB and change in weight.
OBJECTIVE: To measure the independent longitudinal association between weight change and change in SDB severity.
DESIGN: Population-based, prospective cohort study conducted from July 1989 to January 2000.
SETTING AND PARTICIPANTS: Six hundred ninety randomly selected employed Wisconsin residents (mean age at baseline, 46 years; 56% male) who were evaluated twice at 4-year intervals for SDB.
MAIN OUTCOME MEASURES: Percentage change in the apnea-hypopnea index (AHI; apnea events + hypopnea events per hour of sleep) and odds of developing moderate-to-severe SDB (defined by an AHI > or =15 events per hour of sleep), with respect to change in weight.
RESULTS: Relative to stable weight, a 10% weight gain predicted an approximate 32% (95% confidence interval [CI], 20%-45%) increase in the AHI. A 10% weight loss predicted a 26% (95% CI, 18%-34%) decrease in the AHI. A 10% increase in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing moderate-to-severe SDB.
CONCLUSIONS: Our data indicate that clinical and public health programs that result in even modest weight control are likely to be effective in managing SDB and reducing new occurrence of SDB.
Kirstie N Anderson, Samantha Pilsworth, Linda D Sharples, Ian E Smith, John M Shneerson
Idiopathic hypersomnia: a study of 77 cases.
Sleep. 2007 Oct;30(10):1274-81.
Abstract/Text
STUDY OBJECTIVES: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment.
SETTING: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK.
PATIENTS AND DESIGN: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years.
MEASUREMENTS AND RESULTS: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs.
CONCLUSIONS: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.
Yves Dauvilliers
Differential diagnosis in hypersomnia.
Curr Neurol Neurosci Rep. 2006 Mar;6(2):156-62.
Abstract/Text
Hypersomnia includes a group of disorders in which the primary complaint is excessive daytime sleepiness. Chronic hypersomnia is characterized by at least 3 months of excessive sleepiness prior to diagnosis and may affect 4% to 6% of the population. The severity of daytime sleepiness needs to be quantified by subjective scales (at least the Epworth sleepiness scale) and objective tests such as the multiple sleep latency test. Chronic hypersomnia does not correspond to an individual clinical entity but includes numerous different etiologies of hypersomnia as recently reported in the revised International Classification of Sleep Disorders. This review details most of those disorders, including narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time, recurrent hypersomnia, behaviorally induced insufficient sleep syndrome, hypersomnia due to medical condition, hypersomnia due to drug or substance, hypersomnia not due to a substance or known physiologic condition, and also sleep-related disordered breathing and periodic leg movement disorders.
Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group.
Neurology. 2000 Mar 14;54(5):1166-75.
Abstract/Text
OBJECTIVE: This is one of two separate clinical trials to evaluate the efficacy and safety of modafinil, a novel wake-promoting agent, in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.
METHODS: In this 9-week, randomized, placebo-controlled, double-blind, 21-center clinical trial, patients were randomized to receive fixed daily doses of modafinil 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 2-week treatment discontinuation phase was included to evaluate the effects of withdrawal on patients who had been receiving modafinil. A total of 271 patients who were naive to modafinil received study medication in the 9-week trial and 240 patients received study medication in the discontinuation phase.
RESULTS: Treatment with modafinil resulted in significant improvement in two objective measures of EDS: the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Additionally, patient self-assessment of sleepiness was significantly improved, as measured by the Epworth Sleepiness Scale, and level of illness was significantly reduced on the independent clinician assessment, the Clinical Global Impression of Change. Nighttime sleep, monitored by nocturnal polysomnography, was not adversely effected with modafinil treatment compared with placebo treatment. The most frequent adverse experience was headache, which was not significantly greater for modafinil than placebo. During treatment discontinuation, individuals who had been receiving modafinil experienced a return of their EDS to baseline levels. During treatment discontinuation, patients did not experience symptoms associated with amphetamine withdrawal syndrome. For up to 9 weeks of daily use there was no evidence for the development of dependence at the dose levels studied.
CONCLUSION: The data indicate that modafinil has an excellent safety profile and is very well tolerated. Modafinil is an effective treatment for excessive daytime sleepiness in narcolepsy and shows continued efficacy with up to 9 weeks of daily use.
Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. US Modafinil in Narcolepsy Multicenter Study Group.
Ann Neurol. 1998 Jan;43(1):88-97. doi: 10.1002/ana.410430115.
Abstract/Text
Narcolepsy is a central nervous system disorder characterized by excessive daytime sleepiness and cataplexy. This placebo-controlled, double-blind, randomized, parallel-group, 18-center study assessed the efficacy and safety of modafinil, a new wake-promoting drug for treating sleepiness in narcolepsy. Subjects with narcolepsy (n = 283) received daily modafinil, 200 or 400 mg, or placebo, for 9 weeks, followed by an open-label treatment period. Subjective sleepiness was measured with the Epworth Sleepiness Scale. Objective sleepiness was assessed with the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Level of illness was measured with the Clinical Global Impression of Change. Modafinil significantly reduced all measures of sleepiness and was associated with significant improvements in level of illness. Medication-related adverse experiences were few, dose-dependent, and mostly rated mild to moderate. Modafinil taken once daily was a very well tolerated and effective wake-promoting agent in the treatment of excessive daytime somnolence associated with narcolepsy. Modafinil demonstrated an excellent safety profile for up to 40 weeks of open-label treatment and efficacy was maintained, suggesting that tolerance will not develop with long-term use. Modafinil is a pharmacologically and clinically promising compound for the treatment of pathological daytime somnolence.
M Billiard, C Bassetti, Y Dauvilliers, L Dolenc-Groselj, G J Lammers, G Mayer, T Pollmächer, P Reading, K Sonka, EFNS Task Force
EFNS guidelines on management of narcolepsy.
Eur J Neurol. 2006 Oct;13(10):1035-48. doi: 10.1111/j.1468-1331.2006.01473.x.
Abstract/Text
Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.
日本睡眠学会編：ナルコレプシーの診断・治療ガイドライン.
Sophie Lavault, Yves Dauvilliers, Xavier Drouot, Smaranda Leu-Semenescu, Jean-Louis Golmard, Michel Lecendreux, Patricia Franco, Isabelle Arnulf
Benefit and risk of modafinil in idiopathic hypersomnia vs. narcolepsy with cataplexy.
Sleep Med. 2011 Jun;12(6):550-6. doi: 10.1016/j.sleep.2011.03.010. Epub 2011 May 14.
Abstract/Text
BACKGROUND: The benefit/risk ratio of modafinil was recently re-evaluated by the European Medicines Agency and was shown to be negative for idiopathic hypersomnia (IH) because of insufficient data.
OBJECTIVE: To evaluate the benefit/risk ratio of modafinil in idiopathic hypersomnia (with and without long sleep time) vs. narcolepsy/cataplexy.
SUBJECTS AND METHODS: The benefit (Epworth sleepiness score, ESS; visual analog scale, patient and clinician opinions) and risks (habituation, adverse effects) of modafinil were studied in a consecutive clinical cohort of 104 IH patients (59 with long sleep time) and 126 patients with narcolepsy/cataplexy.
RESULTS: Modafinil was the first line treatment in 96-99% of patients. It produced a similar ESS change in IH patients and in narcolepsy patients (-2.6±5.1 vs. -3±5.1) and a similar benefit as estimated by the patients (6.9±2.7 vs. 6.5±2.5 on a visual analog scale) and clinicians. The ESS change was lower in IH patients with long sleep time than in those without. Sudden loss of efficacy and habituation were rare in both groups. Patients with IH reported similar but more frequent adverse effects with modafinil than narcolepsy patients: nervousness (14%), palpitations (13%), and headache (11%).
CONCLUSION: Modafinil has an excellent benefit/risk ratio in idiopathic hypersomnia, with or without long sleep time, similar to its effect on narcolepsy/cataplexy.
Copyright © 2011 Elsevier B.V. All rights reserved.
Merrill S Wise, Donna L Arand, R Robert Auger, Stephen N Brooks, Nathaniel F Watson, American Academy of Sleep Medicine
Treatment of narcolepsy and other hypersomnias of central origin.
Sleep. 2007 Dec;30(12):1712-27.
Abstract/Text
OBJECTIVE: The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin.
METHODS: The task force performed a systematic and comprehensive review of the relevant literature and graded the evidence using the Oxford grading system. This paper discusses the strengths and limitations of the available evidence regarding treatment of these conditions, and summarizes key information about safety of these medications. Our findings provide the foundation for development of evidence-based practice parameters on this topic by the Standards of Practice Committee of the American Academy of Sleep Medicine.
RESULTS: The majority of recent papers in this field provide information about use of modafinil or sodium oxybate for treatment of sleepiness associated with narcolepsy. Several large randomized, placebo-controlled studies indicate that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. We identified no studies that report direct comparison of these newer medications versus traditional stimulants, or that indicate what proportion of patients treated initially with these medications require transition to traditional stimulants or to combination therapy to achieve adequate alertness. As with the traditional stimulants, modafinil and sodium oxybate provide, at best, only moderate improvement in alertness rather than full restoration of alertness in patients with narcolepsy. Several large randomized placebo-controlled studies demonstrate that sodium oxybate is effective for treatment of cataplexy associated with narcolepsy, and earlier studies provide limited data to support the effectiveness of fluoxetine and tricyclic antidepressants for treatment of cataplexy. Our findings indicate that very few reports provide information regarding treatment of special populations such as children, older adults, and pregnant or breastfeeding women. The available literature provides a modest amount of information about improvement in quality of life in association with treatment, patient preferences among the different medications, or patient compliance.
CONCLUSION: Several recent studies provide evidence that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. No studies were identified that report direct comparison of these newer medications with traditional stimulants. Despite significant advances in understanding the pathophysiology of narcolepsy, we do not have an ideal treatment to restore full and sustained alertness. Future investigations should be directed toward development of more effective and better tolerated therapies, and primary prevention.
睡眠呼吸障害研究会編：成人の睡眠時無呼吸症候群診断と治療のためのガイドライン、2005.
T L Giles, T J Lasserson, B J Smith, J White, J Wright, C J Cates
Continuous positive airways pressure for obstructive sleep apnoea in adults.
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001106. doi: 10.1002/14651858.CD001106.pub2. Epub 2006 Jan 25.
Abstract/Text
BACKGROUND: Obstructive sleep apnoea is the periodic reduction (hypopnoea) or cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway during sleep. The main symptom is daytime sleepiness and it has been suggested it is linked to premature death, hypertension, ischaemic heart disease, stroke and road traffic accidents.
OBJECTIVES: The main treatment for sleep apnoea is with the use of continuous positive airways pressure (CPAP), which requires a flow generator and mask. These are used at night to prevent apnoea, hypoxia and sleep disturbance. The objective was to assess the effects of CPAP in the treatment of obstructive sleep apnoea in adults.
SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register and reference lists of articles. We consulted experts in the field. Searches were current to July 2005.
SELECTION CRITERIA: We included randomised trials comparing nocturnal CPAP with an inactive control or oral appliances in adults with obstructive sleep apnoea (an apnoea and hypopnoea index greater than five per hour). Trials had a minimum intervention period of two weeks.
DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two review authors extracted data independently. Study authors were contacted for missing information. Parallel and crossover group trials were analysed separately.
MAIN RESULTS: Thirty-six trials involving 1718 people met the inclusion criteria. Study quality was mixed. Compared with control, CPAP showed significant improvements in objective and subjective sleepiness and several quality of life, cognitive function and depression measures (parallel-group studies: Epworth sleepiness scale (ESS) -3.83 units, 95% CI -4.57 to -3.09; crossover studies: ESS -1.84 units, 95% CI -2.57 to -1.11). Twenty-four hour systolic and diastolic blood pressures were lower with CPAP compared with control (parallel-group trials). Compared with oral appliances, CPAP significantly reduced the apnoea and hypopnoea index (crossover studies: -7.97 events/hr, 95% CI -9.56 to -6.38) and improved sleep efficiency (crossover studies: 2.31%, 95% CI 0.02 to 4.6) and minimum oxygen saturation (4.14%, 95% CI 3.25 to 5.03). Responders to both treatments expressed a strong preference for the oral appliance. However, participants were more likely to withdraw on OA than on CPAP therapy.
AUTHORS' CONCLUSIONS: CPAP is effective in reducing symptoms of sleepiness and improving quality of life measures in people with moderate and severe obstructive sleep apnoea (OSA). It is more effective than oral appliances in reducing respiratory disturbances in these people but subjective outcomes are more equivocal. Certain people tend to prefer oral appliances to CPAP where both are effective. This could be because they offer a more convenient way of controlling OSA. Short-term data indicate that CPAP leads to lower blood pressure than in controls. Long-term data are required for all outcomes in order to determine whether the initial benefits seen in short-term clinical trials persist.
日本循環器学会、日本呼吸器学会、日本呼吸ケア・リハビリテーション学会、日本高血圧学会、日本心臓病学会、日本心不全学会、日本心臓リハビリテーション学会，日本睡眠学会編：循環器領域における睡眠呼吸障害の診断・治療に関するガイドライン、2010.
J W Winkelman, K D Sethi, C A Kushida, P M Becker, J Koester, J J Cappola, J Reess
Efficacy and safety of pramipexole in restless legs syndrome.
Neurology. 2006 Sep 26;67(6):1034-9. doi: 10.1212/01.wnl.0000231513.23919.a1. Epub 2006 Aug 23.
Abstract/Text
OBJECTIVE: To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) METHODS: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) RESULTS: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was -9.3 (1.0) for placebo, -12.8 (1.0) for 0.25 mg/day, -13.8 (1.0) for 0.50 mg/day, and -14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of "very much improved" or "much improved" at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%)
CONCLUSION: As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.
Mauro Manconi, Raffaele Ferri, Marco Zucconi, Alessandro Oldani, Laura Giarolli, Valentina Bottasini, Luigi Ferini-Strambi
Pramipexole versus ropinirole: polysomnographic acute effects in restless legs syndrome.
Mov Disord. 2011 Apr;26(5):892-5. doi: 10.1002/mds.23543. Epub 2011 Mar 2.
Abstract/Text
BACKGROUND: Pramipexole and ropinirole have become the first-line treatment for restless legs syndrome. The aim of this study was to perform the first direct comparison between these two molecules in restless legs syndrome.
METHODS: A double-blind, placebo-controlled, double-night and prospective investigation was carried out in 45 consecutive naïve patients with idiopathic restless legs syndrome. Each patient underwent two consecutive full-night polysomnographies: the first baseline recording was performed without premedication and, before the second recording, first group received a single oral dose of 0.25 mg pramipexole, second group a single oral dose of 0.5 mg ropinirole, and the remaining patients received placebo.
RESULTS AND DISCUSSION: Both dopamine agonists improved restless legs syndrome symptoms and markedly suppressed periodic leg movements during sleep compared to placebo, without significant differences between pramipexole and ropinirole. No significant side effects, except for mild morning nausea (2 patients treated with ropinirole, 3 with pramipexole, and 1 with placebo), were reported.
Copyright © 2011 Movement Disorder Society.
Richard P Allen, Crystal Chen, Diego Garcia-Borreguero, Olli Polo, Sarah DuBrava, Jeffrey Miceli, Lloyd Knapp, John W Winkelman
Comparison of pregabalin with pramipexole for restless legs syndrome.
N Engl J Med. 2014 Feb 13;370(7):621-31. doi: 10.1056/NEJMoa1303646.
Abstract/Text
BACKGROUND: Dopaminergic medications relieve symptoms of the restless legs syndrome (RLS) but have the potential to cause iatrogenic worsening (augmentation) of RLS with long-term treatment. Pregabalin may be an effective alternative.
METHODS: In this 52-week, randomized, double-blind trial, we assessed efficacy and augmentation in patients with RLS who were treated with pregabalin as compared with placebo and pramipexole. Patients were randomly assigned to receive 52 weeks of treatment with pregabalin at a dose of 300 mg per day or pramipexole at a dose of 0.25 mg or 0.5 mg per day or 12 weeks of placebo followed by 40 weeks of randomly assigned active treatment. The primary analyses involved a comparison of pregabalin and placebo over a period of 12 weeks with use of the International RLS (IRLS) Study Group Rating Scale (on which the score ranges from 0 to 40, with a higher score indicating more severe symptoms), the Clinical Global Impression of Improvement scale (which was used to assess the proportion of patients with symptoms that were "very much improved" or "much improved"), and a comparison of rates of augmentation with pregabalin and pramipexole over a period of 40 or 52 weeks of treatment.
RESULTS: A total of 719 participants received daily treatment, 182 with 300 mg of pregabalin, 178 with 0.25 mg of pramipexole, 180 with 0.5 mg of pramipexole, and 179 with placebo. Over a period of 12 weeks, the improvement (reduction) in mean scores on the IRLS scale was greater, by 4.5 points, among participants receiving pregabalin than among those receiving placebo (P<0.001), and the proportion of patients with symptoms that were very much improved or much improved was also greater with pregabalin than with placebo (71.4% vs. 46.8%, P<0.001). The rate of augmentation over a period of 40 or 52 weeks was significantly lower with pregabalin than with pramipexole at a dose of 0.5 mg (2.1% vs. 7.7%, P=0.001) but not at a dose of 0.25 mg (2.1% vs. 5.3%, P=0.08). There were six cases of suicidal ideation in the group receiving pregabalin, three in the group receiving 0.25 mg of pramipexole, and two in the group receiving 0.5 mg of pramipexole.
CONCLUSIONS: Pregabalin provided significantly improved treatment outcomes as compared with placebo, and augmentation rates were significantly lower with pregabalin than with 0.5 mg of pramipexole. (Funded by Pfizer; ClinicalTrials.gov number, NCT00806026.).
L Vignatelli, M Billiard, P Clarenbach, D Garcia-Borreguero, D Kaynak, V Liesiene, C Trenkwalder, P Montagna, EFNS Task Force
EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep.
Eur J Neurol. 2006 Oct;13(10):1049-65. doi: 10.1111/j.1468-1331.2006.01410.x.
Abstract/Text
In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short-term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.
