Search

Associacao Fundo de Incentivo a Pesquisa (AFIP) OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography. Universidade Federal de São Paulo (UNIFESP), Departamento de Psicobiologia, São Paulo/, SP, Brazil Universidade Federal de São Paulo (UNIFESP), Departamento de Psicobiologia, São Paulo/, SP, Brazil Web of Science

Objectives Since there is no consensus definition of sleep onset, we studied different aspects of initial sleep periods in healthy volunteers taking melatonin. Two criteria for sleep latency were used: 10 minutes of uninterrupted sleep and 1.5 minutes of stage 1 sleep. Participants Forty healthy male volunteers (mean age 28 +/- 5 years) were assigned to 2 groups: 30 ingested melatonin and 10 placebo. Design All volunteers underwent an initial polysomnogram (baseline) after a 1-night adaptation period. The next day, the placebo or a 10-mg dose of melatonin was administered for 28 days, 1 hour before sleep time, in double-blind fashion. The second polysomnogram was recorded on day 14. Setting Sleep laboratory Results Chronic melatonin administration led to a significant reduction in sleep latency, using only the criterion 10 minutes of uninterrupted sleep. This effect suggests that melatonin may have a hypnotic effect, and the use of melatonin may lead to better sleep consolidation. Conclusions These results show differences that have clinical implications, since the criteria used to diagnose initial insomnia were based on sleep onset.

Objectives To investigate whether different protocols of sleep deprivation modify sleep perception. Methods The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI). Results There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period ( P 0.05). Both RD and TD groups showed PI similar to controls during the recovery period. Conclusion Selective REM sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception.

This study was undertaken to evaluate the acute effects of single low doses of melatonin given to healthy volunteers in the evening. Six healthy male volunteers (age range 22-24 years) participated in this study, after signing an informed consent form. They received in a double-blind fashion placebo or 0.3 or 1.0 mg melatonin at three fixed times: 18:00, 20:00, and 21:00 hr. Polysomnographic recordings began immediately thereafter, with their being allowed to sleep. Prior to each experimental session and in the following morning, subjects completed a sleep quality questionnaire, the Profile of Mood States, the Stanford Sleepiness Scale, and underwent a visual reaction test. Significant decrease on sleep latencies was found following melatonin treatment at 18:00 and 20:00 hr. In addition, melatonin tended to improve sleep efficiency and to reduce intermittent wakefulness. However, at 21:00 hr, 0.3 mg melatonin increased latency to sleep onset and 1.0 mg melatonin had no effect on sleep variables. Furthermore, melatonin given at different times did not alter subjective sleepiness, mood, and reaction time in the following morning. The results from the present study support the notion that administration of low doses of melatonin, mimicking the nocturnal physiological concentration of this hormone may exert immediate sleep-inducing effects.

The objective of the present study was to assess the toxicology of melatonin (10 mg), administered for 28 days to 40 volunteers randomly assigned to groups receiving either melatonin (N = 30) or placebo (N = 10) in a double-blind fashion. The following measurements were performed: polysomnography (PSG), laboratory examinations, including complete blood count, urinalysis, sodium, potassium and calcium levels, total protein levels, albumin, blood glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), urea, creatinine, uric acid, glutamic-oxalacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT), bilirubin, alkaline phosphatase, gama-glutamic transaminase (GGT), T3, T4, TSH, LH/FSH, cortisol, and melatonin serum concentrations. In addition, the Epworth Somnolence Scale (ESS) and a sleep diary (SD) were also applied to the volunteers 1 wk before each PSG. In addition, the volunteers were asked about possible side effects (SE) that appeared during the treatment. The study was carried out according to the following timetable: Visit 0, filling out the term of consent and inclusion criteria; Visit 1, PSG, laboratory examinations, ESS, SD, melatonin serum concentrations; Visit 2, SD, melatonin serum concentrations, SE; Visit 3, melatonin serum concentrations, PSG, ESS, SE; Visit 4, laboratory examinations, SE, melatonin serum concentrations, SD; and Visit 5, PSG, ESS, SE. Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group. No other differences between the placebo and melatonin groups were obtained. In the present study we did not observe, according to the parameters analyzed, any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study.

OBJECTIVE: As insomnia is highly prevalent, and side effects of medication are well-known, mind-body interventions are increasingly being sought. The objective of this study is to present a narrative review regarding the effects of mind-body interventions for the treatment of insomnia. METHOD: A PubMed search was conducted including only randomized, controlled trials in which the main objective was to treat insomnia. DISCUSSION: Twelve studies were selected. In three of the studies, objective parameters (polysomnography) were analyzed. Mind-body interventions were able to improve sleep efficiency and total sleep time. Most can ameliorate sleep quality; some can reduce the use of hypnotic drugs in those who are dependent on these drugs. CONCLUSION: According to the studies we selected, self-reported sleep was improved by all mind-body treatments, among them yoga, relaxation, Tai Chi Chih and music. Cognitive behavioral therapy seems to be the most effective mind-body intervention. Cognitive behavioral therapy was the only intervention that showed better results than medication. However, considering that only five of the twelve studies chosen reached a score of 3 in the Jadad scale, new studies with a higher methodological quality have to be conducted especially in mind-body interventions that belong to the complementary or alternative medicine field. OBJETIVO: Considerando-se que a insônia é altamente prevalente, e os efeitos colaterais das medicações para seu tratamento são bem conhecidos, pesquisas no campo das intervenções mente-corpo têm sido desenvolvidas. O objetivo deste estudo é apresentar uma revisão narrativa sobre os efeitos das intervenções mente-corpo para o tratamento de insônia. MÉTODO: Uma busca pelo site Pubmed foi conduzida incluindo-se apenas estudos controlados e randomizados nos quais o principal objetivo era o tratamento da insônia. DISCUSSÃO: Doze estudos foram selecionados. Em três deles, parâmetros objetivos (polissonografia) foram analisados. Vários destes estudos mostraram melhora na qualidade do sono; em grupos de usuários de drogas hipnóticas ocorreu redução no uso das mesmas. CONCLUSÃO: De acordo com os estudos selecionados, todas as intervenções mente-corpo melhoraram ao menos a qualidade subjetiva do sono, dentre elas yoga, Tai Chi Chih e música. A terapia comportamental cognitiva parece ser a mais efetiva destas intervenções e foi a única que mostrou melhores resultados que a medicação. Porém, considerando que apenas cinco dos 12 estudos selecionados alcançaram o escore 3 na escala de Jadad, novos estudos com melhor qualidade metodológica precisam ser conduzidos especialmente dentre as intervenções mente-corpo que estão no campo das práticas complementares ou alternativas.

The Brazilian Sleep Association brought together specialists in sleep medicine, in order to develop new guidelines on the diagnosis and treatment of insomnias. The following subjects were discussed: concepts, clinical and psychosocial evaluations, recommendations for polysomnography, pharmacological treatment, behavioral and cognitive therapy, comorbidities and insomnia in children. Four levels of evidence were envisaged: standard, recommended, optional and not recommended. For diagnosing of insomnia, psychosocial and polysomnographic investigation were recommended. For non-pharmacological treatment, cognitive behavioral treatment was considered to be standard, while for pharmacological treatment, zolpidem was indicated as the standard drug because of its hypnotic profile, while zopiclone, trazodone and doxepin were recommended. ____________________________________________________________________________________________________________ ABSTRACT A Associação Brasileira de Sono reuniu especialistas em medicina do sono com o objetivo de desenvolver novas diretrizes no diagnóstico e tratamento das insônias. Nós consideramos quatro níveis de evidência: padrão, recomendado, opcional e não recomendado. Os tópicos abordados foram: conceito, avaliação clínica e psicossocial, indicação da polissonografia, tratamento farmacológico, terapia comportamental cognitiva, comorbidades e insônia na infância. Para o diagnóstico da insônia, foi recomendada uma avaliação psicossocial e a realização da polissonografia, enquanto que no que se refere ao tratamento, foi estabelecido como padrão a indicação da terapia comportamental cognitiva, e, quanto ao tratamento farmacológico, foi indicado o uso do zolpidem como hipnótico padrão, e sendo recomendado o zopiclone, a trazodona e a doxepina.

Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM. This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy.

Background The mechanisms involved in sleep perception are not widely known. Therefore, we believe that investigating this phenomenon is the best way to understand some of the mechanisms involved in several sleep disturbances, particularly insomnias. Objective The objective of our study was to evaluate sleep perception in insomniacs, sleep-disordered breathing (SDB) patients, and healthy volunteers. Our hypothesis was that insomniacs have less sleep perception than healthy individuals and patients with sleep respiratory disorders. Methods We studied 199 individuals who were divided into the following four groups: (1) insomnia group; (2) patients with sleep-disordered breathing; (3) patients with insomnia complaints and an associated sleep respiratory disorder; and (4) healthy individuals with no sleep complaints. All patients were subjected to polysomnography (PSG) followed by a questionnaire addressing their perception about the previous night’s sleep. In addition to analysis of all sleep parameters, we determined sleep perception as the percentage of the ratio between total sleep time perceived by the patient and the total sleep time obtained by PSG. Results Sleep perception was significantly lower in insomnia patients than in sleep-disordered breathing patients or the normal group. In addition, no significant differences across the four groups were observed in sleep efficiency and total sleep time. Conclusions The results showed that the reported sleep perception of insomniacs is lower than that of sleep-disordered breathing patients or normal individuals. We believe that sleep perception is as important as other commonly measured parameters, such as sleep efficiency.

We sought to examine the possible participation of dopaminergic receptors in the phasic events that occur during rapid eye movement (REM) sleep, known as sawtooth waves (STW). These phasic phenomena of REM sleep exhibit a unique morphology and, although they represent a characteristic feature of REM sleep, little is known about the mechanisms which generate them and which are apparently different from rapid eye movements. STW behavior was studied in 10 male volunteers aged 20 to 35 years, who were submitted to polysomnographic monitoring (PSG). On the adaptation night they were submitted to the first PSG and on the second night, to the basal PSG. On the third night the volunteers received placebo or haloperidol and spent the whole night awake. On the fourth night they were submitted to the third PSG. After a 15-day rest period, the volunteers returned to the sleep laboratory and, according to a double-blind crossover randomized design, received haloperidol or placebo and spent the whole night awake, after which they were submitted to the fourth PSG. The volunteers who were given haloperidol combined with sleep deprivation exhibited an elevation of the duration and density of the STW, without significant alterations of the other REM sleep phasic phenomena such as rapid eye movement. These findings suggest that sawtooth waves must have their own generating mechanisms and that the dopaminergic receptors must exert a modulating role since REM sleep deprivation, as well as administration of neuroleptics, produces supersensitivity of dopaminergic receptors.

Rapid eye movements that occur during paradoxical sleep are generated from the brainstem and are modulated by cerebral hemispheres. In an attempt to establish the participation of cerebral hemispheres on rapid eye movements, we carried out a quantitative study of eye movements density in patients bearing hemispheres vascular lesions. The polysomnographic recordings of 24 patients were compared to those of 24 healthy volunteers. Density of rapid eye movements was defined as the porcentage of eye movements during the respective time of paradoxical sleep. Based on the present results, we concluded that: stroke patients with hemispheric lesions displayed increased density of rapid eye movements; there was no difference on the density of rapid eye movements according to the hemispheric lesion; higher density of rapid eye movements was observed in patients with anterior hemispheric lesion.

É relatado um caso de encefalite a vírus, tendo o paciente desenvolvido no decurso da evolução a síndrome de Klüver-Bucy. Inicialmente são feitas considerações a respeito da etiologia do processo virótico, ressaltando cs autores a provável participação do vírus do "herpes simplex" na origem do quadro. Os exames complementares realizados (líquido cefalo cefalorraqueano, eletrencefalograma, tomografia computadorizada e biópsia cerebral) são altamente sugestivos de etiologia virótica. A seguir a síndrome de Klüver-Bucy é analisada nas suas várias vertentes: baixa incidência no ser humano, aspectos clínicos e fisiopatológicos. A case of peculiar form of Klüver-Bucy syndrome is reported. The diagnosis of viral meningoencephalitis was made by the clinical features and by cerebrospinal fluid and histological examination (brain byopsy). The computed tomography and electroencephalographic aspects are analysed. The viral meningoencephalitis was possibly herpetic in nature (herpes simplex virus). The patient here concerned, a woman aged twenty-one years old, during the clinical course of the disease showed insatiable appetite, psychic blindness, oral tendencies, aberrant sexual behavior and hypermetamorphopsia (Klüver-Bucy syndrome). The significance of these features is discussed.