Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review / Aspectos regulatórios e evidências do uso de melatonina em distúrbio do sono e insônia: uma revisão integrativa

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.

The effectiveness of melissa officinalis l. Versus citalopram on quality of life of menopausal women with sleep disorder: a randomized double-blind clinical trial

Abstract Objective The present study aimed to assess the effect of Melissa Officinalis L. (a combination of lemon balm with fennel fruit extract) compared with citalopram and placebo on the quality of life of postmenopausal women with sleep disturbance. Methods The present study is a randomized, double-blind, placebo clinical trial among 60 postmenopausal women with sleep disturbance who were referred to a university hospital from 2017 to 2019. The participants were randomized to receive M. Officinalis L. (500 mg daily), citalopram (30 mg) or placebo once daily for 8 weeks. The Menopause-Specific Quality of Life (MENQOL) questionnaire was self-completed by each participant at baseline and after 8 weeks of the intervention and was compared between groups. Results The mean for all MENQOL domain scores were significantly improved in the M. Officinalis L. group compared with citalopram and placebo (p < 0.001). The mean ± standard deviation (SD) after 8 weeks in the M. Officinalis L., citalopram and placebo groups was 2.2 ± 0.84 versus 0.56 ± 0.58 versus 0.36 ± 0.55 in the vasomotor (p < 0.001), 1.02 ± 0.6 versus 0.28 ± 0.2 versus 0.17 ± 0.1 in the psychomotor-social (p < 0.001), 0.76 ± 0.4 versus 0.25 ± 0.1 versus 0.11 ± 0.1 in the physical and 2.3 ± 1.0 versus 0.35 ± 0.5 versus 0.41 ± 0.5 in the sexual domain, respectively. Conclusions The results revealed that M. Officinalis L. may be recommended for improving the quality of life of menopausal women with sleep disturbance. Trial registration The present study was registered by the name "Comparison of the efficacy of citalopram and compound of Asperugo procumbens and foeniculum vulgare in treatment of menopausal disorders" with the code IRCT2013072714174N1 in the Iranian Registry of Clinical Trials (IRCT).

Prevalence of and pathways to benzodiazepine use in Brazil: the role of depression, sleep, and sedentary lifestyle

Objective: This study aimed to determine the prevalence of benzodiazepine (BZD) use in Brazil and to investigate the direct and indirect effects of alcohol consumption, sedentary lifestyle (SL), depressive symptoms (DS), and sleep dissatisfaction (SD) on BZD use. Methods: The Second Brazilian Alcohol and Drugs Survey (II BNADS) used stratified cluster probabilistic sampling to select 4,607 individuals aged 14 years and older from the Brazilian household population. Results: The lifetime and 12-month prevalence of BZD use was 9.8 and 6.1%, respectively. Older participants (age 40 and older) and women had higher rates. Alcohol use disorder, DS, and SD were significantly more prevalent in BZD users. The parallel multiple mediator model showed a positive direct effect of alcohol consumption on BZD use, with significant positive indirect effects of SL, SD, and DS as simultaneous mediators leading to higher BZD intake. Other statistically significant indirect pathways were DS alone, SD alone, and all of the above except SL. Conclusion: The prevalence of BZD use in Brazil is high compared to that of other countries. Knowledge of the main risk factors and pathways to consumption can guide prevention initiatives and underlie the development of better tailored and effective treatment strategies.

A brief review about melatonin, a pineal hormone

ABSTRACT Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.

Transtornos do sono: atualização (1/2) / Sleep disorders: up to date (1/2)

Esta é uma primeira parte (1/2) da abordagem de fundamentos do sono e transtornos do sono (TS) sobre aspectos: neurobiológicos (neuroanatômicos, neuroquímicos e fisiológicos); clínicos (anamnese e exame físico; exames subjetivos - questionários e escalas; exames objetivos - polissonografia, teste de latências múltiplas e actigrafia). É valorizada a terceira Classificação Internacional dos Transtornos do Sono (ICSD-3) para abordar aspectos clínicos, diagnósticos e terapêuticos, segundo as quatro queixas principais referentes dos TS: Insônia, Sonolência excessiva diurna, Movimentos e comportamentos anormais durante o sono e Incapacidade de dormir na hora desejada. Neste artigo abordamos apenas: 1-Insônia - dificuldade em adormecer ou manter-ser dormindo, acordar cedo, ou um distúrbio na qualidade do sono que faz com que o sono pareça inadequado ou não restaurador; duração: aguda ou crônica; 2- Sonolência excessiva diurna; consequente a distúrbios do sono, privação do sono; distúrbios centrais da hipersonia; distúrbios médicos ou psiquiátricos. (AU)

This is the first part (1/2) on this paper about sleep fundamentals and sleep disorders (TS) questions: neurobiological (neuroanatomical, neurochemical and physiological); clinical (anamnesis and physical examination; subjective exams - questionnaires and scales; objective examinations - polysomnography, multiple latency tests and actigraphy). The third International Classification of Sleep Disorders (ICSD-3) is valued to address clinical, diagnostic and therapeutic aspects, according to the four main complaints regarding TS: Insomnia, Excessive daytime drowsiness, Abnormal movements and behaviors during sleep, and Inability to sleep at the desired time. In this paper, it is discussed the only first two: 1-Insomnia: difficulty falling as-leep, staying asleep, early morning waking, non- restorative sleep, quality of sleep, and amount of sleep; duration: acute or chronic. (AU)

Outpatient treatment of sleep disorders in Alzheimer patients / Tratamento ambulatorial dos transtornos do sono em pacientes com doença de Alzheimer

Sleep disorders are common in patients with Alzheimer dementia and affect the quality of life of patients and of their caregivers. Despite the rising number of studies in the area, almost all of them are about non-pharmacological treatment. Our objective was to review the literature concerning pharmacological and non-pharmacological approaches to treat sleep disorders of elderly patients with Alzheimer dementia in the ambulatory setting. The treatments revised consisted of sleep hygiene and/or use of intense light coupled or not with use of melatonin, cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In addition to the non-pharmacological measures, there is evidence that the use of trazodone may aid the treatment of sleep disorders of older individuals with Alzheimer dementia. More studies are necessary to examine the non-pharmacological and pharmacological treatments revised herein.

Os transtornos do sono são comuns nos pacientes com doença de Alzheimer e interferem na qualidade de vida do paciente e de seu cuidador. Apesar da alta prevalência desses transtornos, existe pouca evidência em relação ao seu tratamento. Nosso objetivo foi revisar a literatura em relação ao tratamento não farmacológico e farmacológico dos transtornos do sono nos idosos com doença de Alzheimer em comunidade. Os tratamentos incluídos consistiram na higiene do sono e/ou no uso da luz intensa, combinados ou não com o uso da melatonina, nos inibidores de acetilcolinesterases, antipsicóticos, hipnóticos ou antidepressivos. Para além das medidas não farmacológicas, há evidência de que o uso da trazodona é efetivo no tratamento dos transtornos do sono de pacientes com doença de Alzheimer. Mais estudos sobre as estratégias farmacológicas e não farmacológicas aqui revisadas ou outras são desejáveis.

Chronic use of benzodiazepines among older adults / Uso crônico de benzodiazepínicos entre idosos

OBJECTIVE To analyze the perception of and motivation for the chronic use of benzodiazepine among older adults. METHODS A qualitative study was conducted on 22 older adults living in Bambuí, MG, Southeastern Brazil, who were taking benzodiazepines and had the clinical and cognitive ability to respond to interview questions. The collected data were analyzed on the basis of the “signs, meanings, and actions” model. RESULTS The main reasons pointed out for the use of benzodiazepines were “nervousness”, “sleep problems”, and “worry” due to family and financial problems, everyday problems, and existential difficulties. None of the interviewees said that they used benzodiazepines in a dose higher than that recommended or had been warned by health professionals about any risks of their continuous use. Different strategies were used to obtain the prescription for the medication, and any physician would prescribe it, indicating that a bond was established with the drug and not with the health professional or healthcare service. Obtaining and consuming the medication turned into a crucial issue because benzodiazepine assumes the status of an essential food, which leads users to not think but sleep. It causes a feeling of relief from their problems such as awareness of human finitude and fragility, existential difficulties, and family problems. CONCLUSIONS Benzodiazepine assumes the characteristics of polyvalence among older adults, which extrapolate specific clinical indications, and of essentiality to deal with life’s problems in old age. Although it relieves the “nerves”, the chronic use of benzodiazepines buffers suffering and prevents older adults from going through the suffering. This shows important difficulties in the organization and planning of strategies that are necessary for minimizing the chronic use in this population. .

OBJETIVO Analisar a percepção e motivação do uso crônico de benzodiazepínicos entre idosos. MÉTODOS Estudo qualitativo desenvolvido com 22 idosos residentes em Bambuí, MG, sob uso de medicação benzodiazepínica e em condições clínicas e cognitivas para responder à entrevista. Os dados coletados foram analisados com base no modelo de “signos, significados e ações”. RESULTADOS As principais razões apontadas para o uso dos benzodiazepínicos foram “nervosismo”, “problemas de sono” e “preocupação”, decorrentes de problemas familiares, financeiros, dificuldades cotidianas e existenciais. Nenhum dos entrevistados referiu utilizar benzodiazepínicos acima das doses recomendadas nem foi alertado pelos profissionais acerca de quaisquer riscos sobre o seu uso continuado. Houve diversidade de estratégias na obtenção da prescrição do medicamento e qualquer médico fornecia a receita, o que indica que o vínculo é estabelecido com o medicamento e não com o profissional ou serviço de saúde. A obtenção e o consumo do medicamento tornam-se uma questão crucial, pois o benzodiazepínico assume a importância de um alimento essencial, que lhes permite não pensar e dormir. Oferece um alívio dos seus problemas, que incluem a consciência da finitude e da fragilidade humanas, dificuldades existenciais e familiares. CONCLUSÕES O benzodiazepínico assume características de polivalência entre os idosos, que extrapolam as indicações clínicas mais precisas, e de essencialidade para lidar com problemas da vida na velhice. Embora alivie o “nervoso”, o uso crônico de benzodiazepínicos tampona o sofrimento e impede a pessoa idosa de enfrentar o que ele representa. ...

Cronobiología, sueño y depresión / Chronobiology, sleep and depression

Luego de una actualización sobre diversos aspectos del ciclo vigilia‑sueño, en el presente trabajo se analiza las consecuencias que tiene su alteración sobre el organismo. Además de las consecuencias neuroendócrinas y cardiovasculares, se hace especialmente hincapié en su efecto sobre el estado de ánimo, y la evidencia que surge sobre su vinculación con los episodios depresivos y trastornos bipolares. Finalmente,se establece, como elemento a tener en cuentapara la terapéutica de dicha patología, el uso de medicación que no solo actúe sobre los neurorreceptores, sino que también reestablezca un ordenado ciclo vigilia‑sueño, como forma de evitar la cronificación y agravamiento de los trastornos anímicos.

Transtornos do sono: visão geral / Sleep disorders: overview

Os transtornos do sono (TS) são um problema clínico relevante. Oobjetivo deste trabalho é compreender as características do ciclovigília-sono e das fases do sono, além de suas manifestações, e conhecera classificação, as abordagens diagnósticas e os tratamentos(farmacológicos ou não) dos TS, para melhor controlá-los, principalmenteem relação a adultos. Critérios comportamentais e fisiológicosdefinirão o ciclo vigília-sono e seus componentes (vigília, sonoREM ou NREM ? N1, N2, N3), que são regulados por mecanismoscerebrais integrados. As quatro queixas principais de sono incluem:(1) insônia (tempo: do início do sono, de manutenção do sono e definal do sono; duração: aguda ou crônica; etiologia: primária ou secundária); (2) sonolência excessiva diurna (provocada por causasprimárias ou secundárias, como narcolepsia, hipersonia idiopáticae apneia obstrutiva do sono, além de várias outras); (3) movimentosou comportamentos anormais durante o sono (como pernasinquietas e transtornos de movimentos periódicos dos membros,bruxismo do sono, transtornos comportamentais do sono REM, sonambulismo, terrores noturnos, excitação confusional, pesadelos);(4) incapacidade de dormir na hora desejada (como fase atrasadado sono, fase avançada do sono, trabalho por turnos; jet lag). A segundaedição da Classificação Internacional de Transtornos do Sono (ICSD-2) classifica os TS em oito categorias principais: insônia; transtornosrespiratórios relacionados com o sono; hipersonias de origemcentral; transtornos do ritmo circadiano; parassonias; transtornos domovimento relacionados com o sono; sintomas isolados e variantesnormais; outros TS. Em relação ao tratamento, em primeiro lugar, énecessário reconhecer a causa do TS e/ou sua comorbidade e verificarse o paciente segue as regras básicas de higiene do sono, depois,se for necessário, considerar o tratamento farmacológico e/ou nãofarmacológico, examinando caso a caso...

The sleep disorders (SD) are relevant clinical problem to be bettermanaged by understanding the characteristics of the wake-sleepcycle and sleep stages, the SD manifestations and their classification,diagnostic and treatment approach (pharmacological or not),all the aims of this paper, mainly regarding adults. Behavioral andphysiological criteria define the wake-sleep cycle and its components(wake, sleep REM or NREM ? N1, N2, N3) that are regulatedby integrated brain mechanisms. The four major sleep complaintsinclude: (1) insomnia (timing: sleep onset, sleep maintenance, sleepoffset; duration: acute or chronic; etiology: primary or secondary);(2) excessive daytime sleepiness (caused by primary or secondarycauses, narcolepsy or idiopathic hypersomnia, and obstructive sleepapnea, besides several other causes); (3) abnormal movements orbehavior during sleep (such as restless leg and periodic limb movementdisorder, sleep bruxism, REM behavior disorders, and otherssuch as sleep walking, sleep terrors, confusional arousal, nightmares);(4) inability to sleep at the desired time (such as delayed sleepphase; advanced sleep phase; shift work; jet lag). The second editionof the International Classification of SD (ICSD-2) classifies SD intoeight major categories: insomnia; sleep related breathing disorders;hypersomnias of central origin; circadian rhythm SD; parasomnias;sleep related movement disorders; isolated symptoms and normalvariants; other SD. Regarding treatment, first, it is necessary to recognizethe cause of the sleep disturbance and/or its comorbidity, and to check if the patient follows basic rules of sleep hygiene, after, if necessary, consider non-pharmacological or/and pharmacological management, examining case by case...

Evaluación del uso inapropiado de medicamentos mediante la aplicación de los Criterios de Beers 2012 en adultos mayores del Hospital de Día Geriátrico del H. N. G. Almenara Irigoyen Enero a Junio 2012 / Evaluation of the inappropriate use of drugs through the application of the criteria of Beers 2012 in older adults of the Geriatric Day Hospital at the N.H.G. Almenara Irigoyen - January to June 2012

OBJETIVOS: Determinar la prevalencia y factores asociados al uso inapropiado de medicamentos mediante la aplicación de los criterios de Beers del 2012 en adultos mayores del hospital de Día Geriátrico del Hospital N. Guillermo Almenara Irigoyen, Lima-Perú. METODOS: Se evaluó el uso inapropiado de medicamentos con la aplicación de Criterios de Beers del 2012 en 150 adultos mayores (edad promedio 78 años) del hospital de Día Geriátrico en el periodo de enero a junto 2012. Se utilizaron pruebas estadísticas simples de frecuencias relativas y absolutas; para determinar la asociación entre variables categóricas se utilizó el test Chi cuadrado y prueba exacta de Fisher y para variables cuantitativas el test de Student con significancia estadística de p<0.05. RESULTADOS: La prevalencia de uso inapropiado de medicamentos fue de 52.7 por ciento. Los medicamentos inapropiados según los criterios de Beers 2012 más frecuentemente utilizados fueron AINES (33 por ciento), sulfonilureas de larga duración (27 por ciento) y benzodiacepinas (20 por ciento). Los medicamentos asociados a interacción droga-enfermedad que se utilizaron con más frecuencia fueron benzodiacepinas y deterioro cognitivo (32 por ciento), calcio antagonistas y estreñimiento (18 por ciento), antagonistas de receptores H2 con deterioro cognitivo y benzodiacepinas con historia de caídas (16 por ciento). La mirtazapina (28.6 por ciento) y la aspirina en mayores de 80 años en prevención primaria (28.6 por ciento) fueron los medicamentos utilizados con precaución más frecuentes. La polifarmacia, síndrome de caídas y trastorno del sueño estuvieron asociados con significancia estadística (p<0.05) a uso inapropiado de medicamentos. Los adultos mayores de sexo femenino, dependencia funcional, más de comorbilidades, depresión y deterioro cognitivo utilizaron frecuentemente medicamentos inapropiados pero sin asociación estadísticamente significativa. CONCLUSIONES: Se determinó la prevalencia elevada de uso...

OBJECTIVE: To determine the prevalence and associated factors of potentially inappropriate medication use defined by the Beers Criteria 2012 among older adults in a Geriatric Day Hospital in Lima-Peru. METHODS: A sample of 150 older adults (mean age 68 years) admitted to the geriatric day hospital between January and June 2012 were included and the inappropriate medication use were evaluated with the Beers Criteria 2012. We use statistics test of relative and absolute frequency and the Chi square test and Fisher exact test to determine the associated factors between qualitative variables and Student Test for quantitative variables, with significance statistic p<0.05. RESULTS: The prevalence of inappropriate medication use was 52.7 per cent. The more common inappropriate medications were NSAIDS (33 per cent), long action sulfonylurea (27 per cent) and benzodiazepines (20 per cent). The more common medication with drug-disease interaction were benzodiazepines with cognitive impairment (32 per cent), constipation and calcium channel blockers (18 per cent), antihistamines of H2 receptors with cognitive impairment and benzodiazepines with previous falls (16 per cent). Mirtazapine (28.6 per cent) and aspirin in over 80 years (28.6 per cent) were the medications more common used with precaution. Polypharmacy, falls, and sleep disturbances were associated with inappropriate medication use and they had significance statistic p<0.05. Female sex, dependence, more than 3 comorbidities, depression, and cognitive impairment were not associated with significance statistic. CONCLUSION: We determine a prevalence of 52.7 per cent of inappropriate medication use in older adults in a geriatric day hospital in Lima Peru. Polypharmacy falls and sleep disturbances were associated with significance statistic.

[ effect of valerian on sleep component among menopausal women]

About 50 percent of menopausal women have sleep problems that can lead to reduced quality of life; according to the population growth in postmenopausal women today, raising the level of their health issues are deemed important. The aim of this study was to investigate the effect of valerian on sleep component among 60-50 year women. In this study, a randomized controlled trial design was employed. Participants consisted of 100 women with menopause aged 50-60, who suffered from insomnia. Instruments included demographic data form and Pittsburg sleep quality index. Descriptive and inferential statistics were used to analyze the data. Prevalence of sleep disorders by Pittsburg sleep quality index in this group was 70%. A statistically significant change was reported in the six component of sleep disturbance in intervention group in comparison to the placebo group [p=0.000]. But the sixth component [the mount of drugs] was not statistically different. The results show that valerian improves the component of sleep in women with insomnia. So, it is essential that health providers would be familiar with these herb supplements

Normalización de trastornos de sueño y su efecto en pacientes con epilepsia refractaria / Effects of sleep disorders normalization in patients during the use of antiepileptic drugs

Los trastornos del sueño son un problema frecuente y subdiagnosticado en niños con cuadros neurológicos y en particular con epilepsias refractarias. Evaluamos los efectos de normalización rápida de los patrones de sueño sobre la refractariedad de la epilepsia. Pacientes y Método: Se ingresaron al estudio todos los pacientes pediátricos con alteración severa del ciclo sueño-vigilia y epilepsia refractaria en control en el Servicio de Neuropsiquiatría Infantil del Hospital Clínico San Borja-Arriarán y Liga contra la Epilepsia, Santiago, Chile, entre Marzo 2004 y Marzo 2008. Cada paciente fue su propio control. Durante el primer mes se solicitó a los padres completar un registro diario de frecuencia y tipo de crisis epiléptica y del ciclo sueño-vigilia de su hijo (a). A contar del segundo mes se implementó un tratamiento para normalizar el ciclo sueño-vigilia utilizando luminoterapia, hábitos estrictos de sueño y melatonina, 30 min antes de la hora de dormir. La terapia antiepiléptica no se modificó durante los primeros seis meses de tratamiento. Resultados: Los once pacientes ingresados normalizaron el ciclo sueño-vigilia durante el primer mes de tratamiento. Diez de 11 casos mostraron una reducción dramática de la frecuencia de crisis por día, mayor a un 85 por ciento, durante los primeros tres meses de intervención, independientemente del tipo de crisis, que se mantuvo por más de un año de seguimiento (13-43 meses). En cinco pacientes se discontinuó la melatonina después de un año de tratamiento, sin que hubiese deterioro del patrón de sueño o aumento en la frecuencia de crisis. Conclusión: Es frecuente el subdiagnóstico de trastorno de sueño en niños con epilepsias refractarias. La normalización del patrón de ciclo sueño-vigilia puede disminuir dramáticamente la frecuencia de crisis y por lo tanto mejorar la calidad de vida de los pacientes y sus familias...

Sleep disorders are a frequent and underdiagnosed problem in children with neurological problems, specially in children with refractory epilepsies. We evaluated the effects of fast normalization of sleep pattern on epilepsy refractoriness. Patients and methods: We enrolled all pediatric patients from March 2004 to March 2008, with severe alterations of the sleep-wake pattern and refractory epilepsy, attending to the Neuropsychiatry Service, Hospital Clínico San Borja-Arriarán and League against Epilepsy from Santiago, Chile. Each patient was his own control. Parents were asked to complete a diary during the first month after enrollment with frequency, type of seizures and sleep-wake cycle of each patient. After the month, sleep-wake cycle was normalized using morning luminotherapy, strict sleep habits and melatonin, 30 minutes before bedtime. Antiepileptic therapy was not modified during the first six months. Results: All patients normalized the sleep-wake cycle during the first month treatment. Ten of 11 patients showed a dramatic reduction of seizure frequency (over 85 percent of total day seizures) during the first three months of intervention, independently from the seizure type that has maintained for more than a year (13–43 months) follow-up. Melatonin was discontinued in five patients after a year of treatment, with no deterioration of sleep pattern or seizures frequency. Conclusions: Sleep disorders in children with refractory epilepsies are frequently underestimated. The normalization of the sleep-wake pattern can diminish seizures dramatically, improving patients and family quality of life. This point must be always taken into account before considering a patient refractory to antiepileptic drugs and adding new drugs to polytherapy.

Sedative antidepressants and insomnia / Antidepressivos sedativos e insônia

OBJECTIVE: The present review addresses the relationship between sleep and depression and how serotonergic transmission is implicated in both conditions. METHOD: Literature searches were performed in the PubMed and MedLine databases up to March 2010. The terms searched were "insomnia", "depression", "sedative antidepressants" and "serotonin". In order to pinpoint the sedative antidepressants most used to treat insomnia, 34 ISI articles, mainly reviews and placebo-controlled clinical trials, were selected from 317 articles found in our primary search. RESULTS: Sleep problems may appear months before the diagnosis of clinical depression and persist after the resolution of depression. Treatment of insomnia symptoms may improve this comorbid disease. Some antidepressant drugs can also result in insomnia or daytime sleepiness. Serotonin (5-HT) demonstrates a complex pattern with respect to sleep and wakefulness that is related to the array of 5-HT receptor subtypes involved in different physiological functions. It is now believed that 5HT2 receptor stimulation is subjacent to insomnia and changes in sleep organization related to the use of some antidepressants. CONCLUSION: Some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from depression. 5-HT2 receptor antagonists are promising drugs for treatment strategies since they can improve comorbid insomnia and depression.

OBJETIVO: Esta atualização aborda a relação entre sono e depressão e como a transmissão serotoninérgica está envolvida em ambas condições. MÉTODO: Foi realizada uma busca na literatura no PubMed e MedLine até março de 2010 com os termos "insônia", "depressão", "antidepressivos sedativos" e "serotonina". A fim de contemplar os antidepressivos sedativos mais utilizados no tratamento da insônia, 34 artigos ISI, principalmente revisões e estudos clínicos placebo-controlados, foram selecionados entre 317 artigos encontrados na busca inicial. RESULTADOS: Alterações de sono podem aparecer meses antes do diagnóstico clínico de depressão e persistir após a resolução da depressão. O tratamento dos sintomas de insônia pode melhorar essa doença associada. Alguns antidepressivos também podem levar à insônia ou sonolência diurna. A serotonina (5-HT) demonstra um padrão complexo no que diz respeito ao sono e vigília, o que está relacionado com a variedade de subtipos do receptor 5-HT envolvidos em diferentes funções fisiológicas. Acredita-se, atualmente, que a estimulação do receptor 5-HT2 esteja envolvida nas alterações da organização do sono e insônia relacionada a alguns antidepressivos. CONCLUSÃO: Alguns medicamentos normalmente prescritos para o tratamento de depressão podem piorar a insônia e dificultar a completa recuperação da depressão. Os antagonistas do receptor 5-HT2 são drogas promissoras para o tratamento, pois podem melhorar a insônia e depressão associadas.

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study / Trazodona para o tratamento de distúrbios do sono em demência: um estudo aberto, observacional e de revisão

Sleep disorders (SD) in patients with dementia are very common in clinical practice. The use of antidepressants with hypnotic actions, such as trazodone, plays an important role in these cases. The aim of this study is to present a profile of the use of trazodone in demented patients with SD, as well as a review of trazodone hydrochloride in SD. We evaluated 178 elderly patients with Alzheimer's disease and other dementias, clinically presenting SD and treated with hypnosedative medications. In the one-year period comprising the study, 68 (38.2 percent) of the 178 had sleep disorders. Most patients (114; 64 percent) had a diagnosis of Alzheimer's disease. Approximately 85 percent of patients with SD used hypnosedative drugs. Trazodone was the most commonly used drug among patients (N = 35), with an effectiveness of 65.7 percent. Trazodone has been shown to be a good option for treatment of the elderly with dementia and associated SD.

Distúrbios do sono (DS) em pacientes com demência são muito comuns na prática clínica. O uso de antidepressivos com ação hipnótica, como a trazodona, tem um papel importante nesses casos. O objetivo desse estudo é apresentar um perfil do uso da trazodona em pacientes com demência e com DS, bem como revisar o cloridrato de trazodona no DS. Nós avaliamos 178 idosos com doença de Alzheimer (DA) e outras demências, clinicamente apresentando DS e que foram tratados com medicações hipnossedativas. No período de um ano de estudo, 68 (38,2 por cento) tiveram DS. A maioria (114; 64 por cento) tinham diagnóstico de DA. Aproximadamente 85 por cento usaram fármacos hipnossedativos. A trazodona foi a mais utilizada (N=35), com evidência de melhora de 65,7 por cento. A trazodona mostrou-se ser uma boa opção no tratamento de idosos com demência e DS associado.

Síndrome de ingesta nocturna como efecto colateral del zolpidem / Sleep related eating disorders as a side effect of zolpidem

El zolpidem es una droga hipnótica utilizada para el tratamiento del insomnio. Disminuye la latencia del sueño, el número total de despertares y aumenta el tiempo total del sueño respetando en general su arquitectura. Se cree que aumenta la fase 3 del sueño lento profundo. Nuestro objetivo es comunicar 8 casos de síndrome de ingesta nocturna relacionado al sueño y conductas automáticas complejas asociadas a sonambulismo como efecto colateral del zolpidem. Se analizaron las historias clínicas de 8 pacientes tratados con zolpidem que referían ingesta nocturna de alimentos con amnesia total o parcial del episodio. Se presentan 6 mujeres y 2 hombres, entre 32 y 72 años (media: 58 años), 7 tratados con zolpidem 10 mg/noche y 1 con zolpidem 12.5 mg/noche de liberación prolongada. El tiempo de exposición previo al desarrollo de eventos fue de 1 a 180 días (media de 39.8). El número de episodios relatados era de 1 a 8/noche (media 2.5) asociado con amnesia. Los episodios desaparecieron por completo en el 100% de los casos al suspender la medicación. El síndrome de ingesta nocturna relacionado al sueño es una parasomnia de sueño lento profundo que consiste en episodios de ingesta de alimento o bebida durante la noche, con amnesia parcial o completa del episodio. El zolpidem podría inducir el síndrome de ingesta nocturna relacionado al sueño en aproximadamente el 1% de pacientes, aunque creemos que es un efecto adverso que está subdiagnosticado. Se resuelve simplemente suspendiendo la medicación.

Zolpidem is a hypnotic drug used in sleep disorders. It binds selectively to alpha 1 subunit of the GABA A benzodiazepine receptor. Zolpidem reduces sleep latency, number of arousals and increases the total time of sleep. However, it is considered that it may increase phase 3 of non rapid eye movement sleep, where somnambulism can take place. Our aim is to report 8 cases of sleep related eating disorders associated with the use of this drug. We have evaluated the medical history of 8 patients who had received zolpidem for sleeping disorders and who have presented sleep related eating disorders. Eight patients (6 women, 2 men) aged between 32 to 72 years old, which received 10 mg of zolpidem/night except 1 that received 12.5 mg, were presented. They have referred strange eating behavior compatible to sleep related eating disorder. Symptoms appeared at a mean of 39.8 days after starting the medication. The numbers of nocturnal episodes recorded by the family or by the patient were 1 to 8 episodes of nocturnal eating per night. The morning after, patients found leftovers from the night before which they did not recall to have eaten. The remission was complete after discontinuing zolpidem. Zolpidem may induce sleep related eating disorder in about 1% of patients, although we consider there may be a subdiagnosis of this phenomenon. It will be important to bear in mind and look for this side effect because all the episodes could easily be controlled by withdrawing the drug.

Neurofisiologia do sono e aspectos farmacoterapêuticos dos seus transtornos: [revisão] / Neurophysiology of sleep and pharmacotherapeutic aspects of their disorders: [review]

Objetivos. Avaliar processos homeostáticos e circadianos e tratos/vias neurais implicados no ciclo sono-vigília; transmissores e receptores neuronais específicos que compõem sistema reticular ativador ascendente; neurônios ativos para a promoção do sono; interação mutuamente inibitória entre os sistemas do despertar e do sono; bases celulares do estado do sono e expressão no EEG; implicações farmacoterapêuticas para controle dos transtornos do sono (TS). Métodos. Revisão baseada em artigos publicados principalmente nos últimos cinco anos sobre neurofisiologia do sono e aspectos farmacoterapêuticos dos seus transtornos. Resultados. O ciclo sono-vigília é controlado por mecanismos integrados regulados pelo ritmo circadiano e por substâncias hipnogênicas endógenas. O controle e a regulação das diferentes fases do sono e da vigília são mediados através da interação coordenada entre diferentes sistemas neurais e diversos neurotransmissores. De modo geral, o sistema que promove o sono se localiza no hipotálamo anterior (núcleo pré-óptico ventrolateral, que serve como comutador do tronco cerebral) e os mecanismos principais do despertar são localizados no hipotálamo posterior/lateral e na parte rostral do tronco cerebral (com produção de acetilcolina, noradrenalina, dopamina, serotonina, histamina e orexina/hipocretina). A ação dos fármacos se faz principalmente através da ação de sistemas de promoção ou inibição da vigília ou sono, de acordo com o tipo de TS, com efeitos que possam aliviar esses transtornos (p. ex.: parassonias).

Objectives. To evaluate homeostatic and circadian processes besides neural pathways implicated in the sleep-wake cycle; transmitters and specific neuronal receptors that comprise the ascending reticular activating system; active neurons that promote sleep; cellular basis of the brain state and EEG; interaction between the mutually inhibitory systems of awakening and sleeping; pharmacotherapeutic control of sleep disorders (SD). Methods. Review based on papers published mainly in the last five years on the neurophysiology of sleep and pharmacotherapeutic aspects of its disorders. Results. The sleep-wake cycle is controlled by integrated mechanisms that are regulated by circadian rhythm and endogenous hypnogenic substances. The control and regulation of different sleep stages and wakefulness are mediated through coordinated interaction between different neural systems and various neurotransmitters. In general, the system that promotes sleep is located in the anteriorhypothalamus (ventrolateral preoptic nucleus that serves as a switch of the brainstem) and the main mechanisms of arousal are located in the posterior/lateral hypothalamus and the rostral brainstem (with production of acetylcholine, norepinephrine, dopamine, serotonin, histamine and orexin/hypocretin). The action of drugs is mainly through systems that promote or reduce sleep or wakefulness, according to the SD type, with effects that may alleviate these disorders (eg.: Parasomnias).

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.