Melatonina en trastornos del sueño: comparación de distintos productos y revisión bibliográfica / Melatonin in sleep disorders. comparison of different products and literature review

Introducción: los trastornos del sueño en Pediatría son un problema creciente. La melatonina es el producto de elección y es común recibir publicidad de múltiples productos que la contienen. En este texto se lleva a cabo un análisis comparativo de los mismos, examinando la evidencia científica más reciente, con el fin de determinar si está justificado o no su uso. Métodos: se ha realizado un estudio descriptivo de los productos que contenían melatonina comercializados en España, de venta en farmacias y dirigidos a la población pediátrica. Posteriormente, se ha llevado a cabo una revisión de documentos sobre el uso de melatonina en niños y sobre cada componente extra presente en los productos recogidos. Resultados: se analizaron 53 productos. La forma de administración mayoritaria fue en gotas o mililitros. La dosis recomendada habitual de melatonina fue de 1 mg al día. El componente añadido más frecuente registrado fue la vitamina B6, y melisa y pasiflora fueron las plantas más utilizadas. Ninguno de los productos estaba catalogado como fármaco por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) y tampoco se encontró en la publicidad de ninguno referencias bibliográficas. Conclusiones: aunque es conocida la eficacia de la melatonina en trastornos del sueño, actualmente no hay un consenso sobre su dosis eficaz en edad pediátrica. Las sustancias que más frecuentemente se asocian a melatonina cuentan con poca bibliografía que respalde sus resultados sobre el sueño, además de que para ellas tampoco existen, de momento, dosis estandarizadas para la población infantil. (AU)

Introduction: sleep disorders in paediatrics are a growing problem. Melatonin is the drug of choice and it is common to receive advertising for multiple products containing melatonin in primary care. In this paper, a comparative analysis of these products is carried out, examining the most recent scientific evidence, in order to determine whether their use is justified or not. Methods: a descriptive study was conducted on melatonin-containing products sold in pharmacies in Spain and aimed at the paediatric population. Subsequently, a systematic review of documents on the use of melatonin in children and on each extra component present in the products collected was carried out. Results: fifty-three products were analysed. The most common form of administration was drops or millilitres. The usual recommended dose of melatonin was 1 mg per day. The most frequently reported added component was vitamin B6, and lemon balm and passionflower were the most frequently used herbs. None of the products were specifically listed in the Spanish Agency for Medicines and Health Products, and no bibliographical references were found in the advertising of any of the products. Conclusions: although the efficacy of melatonin in sleep disorders is well known, there is currently no consensus on its effective dose in children. The substances most frequently associated with melatonin have little literature to support their results in sleep, and there are no standardised doses for them either, or doses lower than these are used due to a lack of studies in the paediatric population. (AU)

Alleviating sleep disturbances and modulating neuronal activity after ischemia: Evidence for the benefits of zolpidem in stroke recovery.

AIMS: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear. METHOD: Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity. RESULTS: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side. CONCLUSION: Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.

Trauma Exposure in Migrant Children: Impact on Sleep and Acute Treatment Interventions.

Trauma exposure significantly impacts sleep in children. Nightmares are common. Evidence-based therapies are superior to medications but may not always be available in acute settings. No FDA-approved medications exist for the treatment of trauma-related sleep disturbances in youth. The evidence-base for the use of medications is largely based on case reports, retrospective chart reviews, clinical opinion, and adult studies. This evidence is reviewed for a number of medications, including prazosin, trazodone, alpha-2 agonists, quetiapine, and others.

Elevated prevalence and treatment of sleep disorders from 2011 to 2020: a nationwide population-based retrospective cohort study in Korea.

OBJECTIVES: This study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last 10 years. METHODS: This is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses and prescribed amounts for sleep disorders were recorded. RESULTS: The prevalence of sleep disorders increased from 3 867 975 (7.62%) in 2011 to 7 446 846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9 011 692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine. CONCLUSIONS: Sleep disorders are continuously increasing, as is the use of medical services-personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognised as a significant health problem that needs to be actively addressed to improve quality of life.

Melatonin treatment has consistent but transient beneficial effects on sleep measures and pain in patients with severe chronic pain: the DREAM-CP randomised controlled trial.

BACKGROUND: Sleep disturbance is a major issue for patients with chronic pain. Melatonin has been shown to improve symptoms of fibromyalgia, but its efficacy in other chronic non-malignant pain conditions is not fully known. Hence, we determined the effect of melatonin in patients with severe noncancer chronic pain. METHODS: This was a randomised double-blinded crossover trial of modified-release melatonin as Circadin™ compared with placebo. Sixty male and female subjects with chronic severe pain were randomised to receive either 2 mg of Circadin™ or placebo before sleep for 6 weeks, followed by a >4 week washout, then crossing over to the other treatment. Sleep disturbance, quality, and latency were measured using three different validated sleep assessment tools. The primary outcome measure was self-reported sleep disturbance after 6 weeks of treatment. Adverse events were also recorded. RESULTS: Sleep disturbance after 6 weeks was not significantly altered by melatonin treatment, but differences between melatonin and placebo treatment periods after 3 weeks were seen: sleep disturbance (P=0.014), latency (P=0.04), overall sleep quality (P=0.004), and effect of pain on sleep (P=0.032). Pain intensity scores improved during both treatment periods (both P<0.001). There were no differences in adverse events between treatment periods. CONCLUSIONS: Circadin™ treatment did not improve sleep disturbance in patients with severe chronic pain compared with placebo at 6 weeks, but there were consistent improvements in aspects of sleep in the shorter term. Given its favourable safety profile, it could be beneficial for some patients with chronic pain. CLINICAL TRIAL REGISTRATION: ISRCTN12861060.

Examining daily stimulant medication use and sleep in adolescents with ADHD.

Research has been inconclusive as to whether stimulant treatment causes or exacerbates sleep problems in adolescents with ADHD. This study examined sleep differences in adolescents with ADHD as a function of stimulant use. Participants were adolescents with ADHD (N = 159, ages 12-14). Parents reported on receipt of stimulant treatment (n = 92, 57.86%; n = 47 amphetamines, n = 45 methylphenidate). Adolescents wore actigraphs and completed daily diaries assessing sleep and daily use of stimulants for 2 weeks. Sleep parameters included daily-reported bedtime, sleep onset latency (SOL), sleep duration, daytime sleepiness, and difficulty waking the following morning; and actigraphy-measured sleep onset time, total time in bed, and sleep efficiency. We estimated between- and within-individual associations between stimulant medication use and sleep indices with all stimulants, after removing adolescents using sleep aids and weekend days, and as a function of stimulant type. Adolescent sleep did not differ between those receiving and not receiving stimulant treatment. Within individuals using stimulants, we largely observed no significant differences between medicated and unmedicated days, though findings were most often significant for school days only. Small effects were found indicating longer SOL, later sleep onset time, and more daytime sleepiness related to medication use. In contrast, there were slight improvements to sleep duration and sleep efficiency related to methylphenidate use, though methylphenidate was also associated with later sleep onset time and more daytime sleepiness. Given the inconsistent and small effects, findings suggest that stimulant medication may impact sleep, but does not appear to be a primary contributor to sleep problems in adolescents with ADHD.

Therapeutic potential of melatonin in targeting molecular pathways of organ fibrosis.

Fibrosis, the excessive deposition of fibrous connective tissue in an organ in response to injury, is a pathological condition affecting many individuals worldwide. Fibrosis causes the failure of tissue function and is largely irreversible as the disease progresses. Pharmacologic treatment options for organ fibrosis are limited, but studies suggest that antioxidants, particularly melatonin, can aid in preventing and controlling fibrotic damage to the organs. Melatonin, an indole nocturnally released from the pineal gland, is commonly used to regulate circadian and seasonal biological rhythms and is indicated for treating sleep disorders. While it is often effective in treating sleep disorders, melatonin's anti-inflammatory and antioxidant properties also make it a promising molecule for treating other disorders such as organ fibrosis. Melatonin ameliorates the necrotic and apoptotic changes that lead to fibrosis in various organs including the heart, liver, lung, and kidney. Moreover, melatonin reduces the infiltration of inflammatory cells during fibrosis development. This article outlines the protective effects of melatonin against fibrosis, including its safety and potential therapeutic effects. The goal of this article is to provide a summary of data accumulated to date and to encourage further experimentation with melatonin and increase its use as an anti-fibrotic agent in clinical settings.

Genetics of sleep medication purchases suggests causality from sleep problems to psychiatric traits.

STUDY OBJECTIVES: Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems. METHODS: We performed epidemiological analysis for psychiatric diagnoses, and genetic association studies of sleep medication purchase in 797 714 individuals from FinnGen Release 7 (N = 311 892) and from the UK Biobank (N = 485 822). Post-association analyses included genetic correlation, co-localization, Mendelian randomization (MR), and polygenic risk estimation. RESULTS: In a GWAS we identified 27 genetic loci significantly associated with sleep medication, located in genes associated with sleep; AUTS2, CACNA1C, MEIS1, KIRREL3, PAX8, GABRA2, psychiatric traits; CACNA1C, HIST1H2BD, NUDT12. TOPAZ1 and TSNARE1. Co-localization and expression analysis emphasized effects on the KPNA2, GABRA2, and CACNA1C expression in the brain. Sleep medications use was epidemiologically related to psychiatric traits in FinnGen (OR [95% (CI)] = 3.86 [3.78 to 3.94], p < 2 × 10-16), and the association was accentuated by genetic correlation and MR; depression (rg = 0.55 (0.027), p = 2.86 × 10-89, p MR = 4.5 × 10-5), schizophrenia (rg = 0.25 (0.026), p = 2.52 × 10-21, p MR = 2 × 10-4), and anxiety (rg = 0.44 (0.047), p = 2.88 × 10-27, p MR = 8.6 × 10-12). CONCLUSIONS: These results demonstrate the genetics behind sleep problems and the association between sleep problems and psychiatric traits. Our results highlight the scientific basis for sleep management in treating the impact of psychiatric diseases.

The association between wealth and sleep medication use in a nationally-representative sample of older Medicare beneficiaries.

BACKGROUND: Sleep disorders are common among older adults, leading to high prevalence of over-the-counter and prescription sleep medication use. Socioeconomically disadvantaged individuals have higher prevalence of sleep disorders. Frequent use of sleep medications can increase the risk of falls. Little is known about the association between wealth and sleep medication use in older adults. METHODS: We conducted a cross-sectional analysis using a nationwide sample of 7603 Medicare beneficiaries (65+ years) from Round 1 (2011) of the National Health and Aging Trends Study. We measured self-reported wealth as the sum of assets (retirement savings, stocks/bonds, checking/savings accounts, business assets, and home value) minus liabilities (mortgage, credit card, and medical debt). Self-reported sleep medication use in the past month was categorized as frequent (5-7 nights/week), sometimes (1-4 nights/week), or never (0 night/week). We estimated differences in the prevalence of sleep medication use by quintiles of wealth using crude and adjusted binomial regression models. Individuals missing sleep medication information were excluded. RESULTS: Median wealth was $152 582 (IQR: $24 023-412 992). Sixteen percent reported frequent sleep medication use, 15% reported some use, and 70% reported no use. Frequent sleep medication use was more common in lower wealth quintiles (lowest: 20%, highest: 12%). Alternatively, some use was more common in higher wealth quintiles (lowest: 11%, highest: 18%). Results were similar after adjustment for demographic factors, anxiety, depression, and sleep disorders. CONCLUSIONS: In this study, less wealthy older adults had higher prevalence of frequent sleep medication use. This may lead to dependency or increased fall risk in this vulnerable population.

Hypnosis Intervention for Sleep Disturbances in Individuals with Mild Cognitive Impairment: A Randomized Pilot Study.

Poor sleep quality is highly prevalent among individuals with mild cognitive impairment (MCI). Further, poor sleep quality is associated with reduced quality of life, increased stress response, memory impairments, and progression to dementia among individuals with MCI. Pharmacological treatments for sleep have mixed efficacy and can lead to dependency. Therefore, alternatives to pharmacological treatments for improving sleep among individuals with MCI are needed. The present study reports on the feasibility of a non-pharmacological self-administered hypnosis intervention focused on sleep quality in adults with MCI. It was hypothesized that the hypnosis intervention program would be feasible and have acceptable levels of adherence to daily hypnosis practice. A two-armed randomized controlled pilot trial was conducted using a sample of 21 adults with MCI. Eligible participants were randomly assigned to listen to either hypnosis audio recordings or sham hypnosis recordings for five weeks. Program feasibility, program adherence, pain intensity, stress, and sleep quality were measured using a daily home practice log, questionnaires, and wrist actigraphy. The results found mid or higher levels of treatment satisfaction, ease of use, and perceived effectiveness at one-week follow-up, with participants in the hypnosis arm reporting greater perceived benefit. Adherence to assigned audio recordings and meetings were likewise within acceptable margins in both groups. No intervention-related adverse events were reported in either treatment condition. Significant improvements in sleep quality, sleep duration, and daytime sleepiness were found for the hypnosis intervention. The results of this study can be used to inform future research on the effects of hypnosis on sleep quality in adults with MCI.

Sleep Quality After Quetiapine Augmentation in Patients With Treatment-Resistant Depression and Personality Disorders.

PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-). METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02). IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.

A mouse model of sleep disorders in Parkinson's disease showing distinct effects of dopamine D2-like receptor activation.

Excessive daytime sleepiness (EDS) and sleep fragmentation are often observed in Parkinson's disease (PD) patients and are poorly understood despite their considerable impact on quality of life. We examined the ability of a neurotoxin-based mouse model of PD to reproduce these disorders and tested the potential counteracting effects of dopamine replacement therapy. Experiments were conducted in female mice with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, leading to the loss of dopamine neurons projecting to the dorsal and ventral striatum. Sham-operated mice were used as control. Electroencephalographic and electromyographic recording was used to identify and quantify awaken, rapid eye movement (REM) and non-REM (NREM) sleep states. PD mice displayed enhanced NREM sleep and reduced wakefulness during the active period of the 24-hour circadian cycle, indicative of EDS. In addition, they also showed fragmentation of NREM sleep and increased slow-wave activity, a marker of sleep pressure. Electroencephalographic analysis of the PD model also revealed decreased density and increased length of burst-like thalamocortical oscillations (spindles). Treatment of PD mice with the dopamine receptor agonist, pramipexole, but not with L-DOPA, counteracted EDS by reducing the number, but not the length, of NREM sleep episodes during the first half of the active period. The present model recapitulates some prominent PD-related anomalies affecting sleep macro- and micro-structure. Based on the pharmacological profile of pramipexole these results also indicate the involvement of impaired dopamine D2/D3 receptor transmission in EDS.

Clinical observation of dexmedetomidine nasal spray in the treatment of sleep disorders on the first night after undergoing maxillofacial surgery: a single-center double-blind randomized controlled study.

Purpose: Dexmedetomidine exerts a sedative effect by promoting the sleep pathway endogenously and producing a state similar to N2 sleep. This study aimed to study the efficacy and safety of dexmedetomidine nasal spray in the treatment of postoperative sleep disturbance. Methods: This study enrolled 120 participants [men and women; age, 18-40 years; American Society of Anesthesiologists grade, I or II] who underwent maxillofacial surgery under general anesthesia through nasotracheal intubation. The participants were randomly divided into three groups: blank control group (BC group), 1.0 µg/kg dexmedetomidine group (1.0 Dex group), and 1.5 µg/kg dexmedetomidine group (1.5 Dex group), with 40 patients allocated to each group. At 21:30 on the night after the operation, the intervention groups were administered their corresponding doses of dexmedetomidine nasal spray. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate the baseline sleep status of participants 1 month preoperatively and on the night after the operation. Polysomnography (PSG) was used to record the sleep status on the night after the operation. We recorded the rescue times of sedative and analgesic drugs on the first night after surgery, adverse reactions, total hospital stay duration, and total costs. Results: Compared with patients in the BC group, those in 1.0 Dex and 1.5 Dex groups had longer N2 sleep duration, were awake for a shorter time after dose administration, woke up less often, and had significantly improved sleep efficiency (p < 0.05). Compared with the BC group, the PSQI scores of 1.0 Dex and 1.5 Dex groups were significantly lower on the night after operation, and the proportion of PSQI > 5 was significantly lower (p < 0.05). Compared with patients in the BC group and the 1.0 Dex group, those in the 1.5 Dex group had significantly prolonged N3 sleep, reduced frequency of requiring sufentanil rescue, lower incidence of sore throat after surgery, and shorter average length of hospital stay (all, p < 0.05). Conclusion: The sleep quality of participants on the night after having undergone maxillofacial surgery was safely and effectively improved by 1.0-1.5 µg/kg dexmedetomidine atomized nasal sprays. Notably, only the latter could prolong N3 sleep. Level of Evidence II: Evidence was obtained from at least one properly designed randomized controlled trial.

Using pharmacotherapy to address sleep disturbances in autism spectrum disorders.

INTRODUCTION: Sleep disorders are the second most common medical comorbidity in autism spectrum disorder (ASD), with effects on daytime behavior and functioning, mood and anxiety, and autism core features. In children with ASD, insomnia also has a negative impact on the whole family's quality of life. Therefore, treatment of sleep disturbances should be considered as a primary goal in the management of ASD patients, and it is important to clarify the scientific evidence to inappropriate treatments. AREAS COVERED: The authors review the current literature concerning the pharmacological treatment options for the management of sleep-related disorders in patients with ASD (aged 0-18 years) using the PubMed and Cochrane Library databases with the search terms: autism, autistic, autism spectrum disorder, ASD, drug, drug therapy, drug intervention, drug treatment, pharmacotherapy, pharmacological treatment, pharmacological therapy, pharmacological intervention, sleep, sleep disturbance, and sleep disorder. EXPERT OPINION: Currently, clinicians tend to select medications for the treatment of sleep disorders in ASD based on the first-hand experience of psychiatrists and pediatricians as well as expert opinion. Nevertheless, at the present time, the only compound for which there is sufficient evidence is melatonin, although antihistamines, trazodone, clonidine, ramelteon, gabapentin, or suvorexant can also be considered for selection.

A Randomized, Double-Blind, Placebo-Controlled Decentralized Trial to Assess Sleep, Health Outcomes, and Overall Well-Being in Healthy Adults Reporting Disturbed Sleep, Taking a Melatonin-Free Supplement.

Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N = 620) seeking better sleep were randomly assigned to receive one of three study products. Sleep A (contained lower (0.35 mg THC and higher levels of botanicals (75 mg each hops oil and valerian oil), Sleep B (contained higher THC (0.85 mg) and lower botanicals (20 mg each hops oil and valerian oil) or placebo) for 4 weeks. Sleep disturbance was assessed at baseline and weekly using NIH's Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.

Parental drinking, mental health and educational level, and offspring's subsequent prescription drugs treatment for sleep problems. A longitudinal HUNT survey and registry study.

BACKGROUND: Parental drinking, mental health and family socioeconomic status are all associated with offspring sleep problems, but there is a paucity of research that considers the effect of risk factors, as they co-occur within and across families. Also, sleep problems are closely linked with mental health problems. Disentangling the effects on one or the other are important. We examined whether parental risk constellations are differently associated with offspring's subsequent prescription drug use for sleep problems during nine years with or without prescription drug use for anxiety and/or depression. METHODS: The sample included 8773 adolescent offspring of 6696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway. The exposures were five parental risk constellations, previously identified via Latent Profile Analysis, characterized by drinking frequencies and quantities, mental health, and years of education. The outcomes were dispensed prescription drugs in offspring during 2008-2016 for (a) only sleep problems (b) sleep problems and anxiety/depression or (c) only anxiety/depression. We used multinomial logistic regression to model the odds of the outcomes. RESULTS: Compared to the overall low-risk parental constellation, none of the risky constellations were significantly associated with increased risk of being dispensed prescription drugs only for sleep problems. Offspring from two different risk profiles were at increased risk for being dispensed both sleep and anxiety/depression prescription drugs. These were parental profiles marked by (1) low education, symptoms of mental health problems and weekly binge drinking in both parents (OR 1.90, CI = 1.06;3.42); and (2) frequent heavy drinking in both parents and symptoms of mental health problems in fathers (OR 3.32, CI = 1.49;7.39). Offspring from the risk profile with lowest parental education had increased risk of only anxiety/depression prescription drugs (OR 1.25, CI = 1.05;1.49). CONCLUSION: Our findings suggest that parental risk constellations are not associated with increased risk of offspring receiving sleep medications without also receiving anxiety/depression medications, as two risk constellations were associated with increased risk of dispensation of both sleep and anxiety/depression prescription drugs. Receiving both may be an indication of severity. The findings underscore the importance of including measures of mental health problems when investigating sleep problems to avoid misattribution of effects.

[Sleep regulation as a complex process]. / Regulyatsiya sna kak kompleksnyi protsess.

A retrospective analysis of views on the regulation of the «sleep-wakefulness¼ cycle from the reticular theory of sleep to the Saper's model was carried out. A modified version of the Saper's trigger made it possible to use the results of a comparative analysis of drugs used in the treatment of sleep disorders to develop new, comprehensive, effective approaches to the pharmacotherapy of the most common sleep disorders. It seems that this approach will be useful in the development of effective pharmacotherapy for sleep disorders.

[The impact of antiepileptic therapy on sleep disorders in women with epilepsy]. / Vliyanie protivoepilepticheskoi terapii na narusheniya sna u zhenshchin s epilepsiei.

OBJECTIVE: To analyze the frequency of various sleep disorders in patients with epilepsy receiving antiepileptic therapy. MATERIAL AND METHODS: Sixty-four women were selected from the register of patients with epilepsy and other paroxysmal conditions. The group consisted of young and middle-aged women (36.9±13.5 years), all patients received antiepileptic therapy. To diagnose sleep disorders, we used a sequential algorithm for clinical examination supplemented by instrumental methods according to indications (polysomnography, respiratory monitoring). RESULTS: The duration of epilepsy was 15.7±7.6 years, the disease was represented by three forms: structural (n=15, 23.4%), genetic (n=32, 50%) and unspecified (n=17, 26.6%). Sleep disorders were common among female patients with epilepsy (43.7%), they are most frequently combined with genetic epilepsy (18.7%), and represented by: insomnia (43%) mild to moderately severe breathing disorders (32%) and sleep movement disorders (25%). Sleep disorders were combined with symptoms of depression in the majority of patients (71%). A 6-month follow-up evaluation of nighttime sleep parameters after treatment showed a decrease in the frequency of sleep disorders to 25%; scores on the Epworth Sleepiness Scale significantly decreased to 6.7±3.6. A change in antiepileptic therapy in patients with sleep breathing disorders resulted in a marked regression of the Apnea-Hypopnea Index (9.2±2.5 points; p=0.003). However, there were no significant changes in the severity of sleep movement disorders. CONCLUSION: Sleep disorders are common in patients with epilepsy, in most cases they are associated with mood disorders, and may regress after optimization of antiepileptic therapy.