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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinuation is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addiction have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescribers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discontinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescribers.This review sets out the stratagems that have been evaluated, concentrating on those of a pharmacological nature. Simple interventions include basic monitoring of repeat prescriptions and assessment by the doctor. Even a letter from the primary-care practitioner pointing out the continuing usage of benzodiazepines and questioning their need can result in reduction or cessation of use. Pharmacists also have a role to play in monitoring the use of benzodiazepines, although mobilizing their assistance is not yet routine. Such stratagems can avoid the use of specialist back-up services such as psychiatrists, home care, and addiction and alcohol misuse treatment facilities.Pharmacological interventions for benzodiazepine dependence have been reviewed in detail in a recent Cochrane review, but only eight studies proved adequate for analysis. Carbamazepine was the only drug that appeared to have any useful adjunctive properties for assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one.
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PMID:Withdrawing benzodiazepines in primary care. 1906 73

Several novel melatonin receptor agonists, in addition to various formulations of melatonin itself, are either available or in development for the treatment of insomnia. Melatonin is thought to exert its effects principally through two high affinity, G-protein coupled receptors, MT1 and MT2, though it is not known which subtype is responsible for the sleep-promoting action. The present study used radiotelemetry to record EEG and EMG in un-restrained freely moving rats to monitor the sleep-wake behaviour and examined the acute sleep-promoting activity of an MT2 receptor subtype selective melatonin analog, IIK7. IIK7 is a full agonist at the MT2 receptor subtype but a partial agonist at the MT1 receptor and has approximately 90-fold higher affinity for MT2 than MT1. Like melatonin, IIK7 (10mg/kg i.p.) significantly reduced NREM sleep onset latency and transiently increased the time spent in NREM sleep, but did not alter REM sleep latency or the amount of REM sleep. An analysis of the EEG power spectrum showed no change in delta (1-4 Hz) or theta activity (5-8 Hz) following IIK7 administration. Core body temperature was slightly decreased ( approximately 0.3 degrees C) by IIK7 compared to vehicle-treated rats. The acute and transient changes in the sleep-wake cycle mimic the changes seen with melatonin and suggest that its sleep-promoting activity is mediated by activation of the MT2 receptor subtype.
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PMID:Sleep-promoting action of IIK7, a selective MT2 melatonin receptor agonist in the rat. 1942 70

Insomnia is the most common sleep condition. Many hypnotics decrease nocturnal melatonin secretion. The aim of this research consists of studying the effect of the hypnotic drug zaleplon on melatonin secretion. Twelve non-smoker drug-free healthy male subjects participated in the study. All participants were normal sleepers and aged 33.2 +/- 11.7 years. They orally took 10 mg of zaleplon at 22:00 h in a double-blind, randomized, cross-over design. The study was carried out during two consecutive days in a week-end. Blood samples were extracted at 22:00, 23:00, 24:00, 01:00, 02:00 and 12:00 h. Melatonin was measured by an ELISA assay. All the subjects had a circadian rhythm of melatonin secretion. Zaleplon compared to placebo increased significantly the melatonin levels at 23:00, 24:00 and 01:00 h. No differences in melatonin levels between placebo and zaleplon were found at 12:00, 22:00 and 02:00 h. Zaleplon compared to placebo increased by 46% the Area Under the Curve of melatonin secretion. The present study indicates that zaleplon increases nocturnal melatonin secretion without increasing daytime melatonin levels. We suggest that when clinicians prescribe a hypnotic, the effect on melatonin levels should be another parameter to be taken into account.
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PMID:Zaleplon increases nocturnal melatonin secretion in humans. 1946 83

Studies on the role and the use of melatonin in the treatment of various diseases are considered to be of great interest to date. Melatonin is a hormone with unique adaptive potential; its abnormal production and secretion rhythm trigger the mechanism of desynchronosis leading to organic pathology. Impaired melatonin secretion is observed in subjects with insomnia, cardiovascular and digestive disorders, it occurs during seasonal exacerbation of chronic diseases and in patients with hormone-dependent tumours. Understanding the role of melatonin in pathogenesis of different diseases may facilitate its use for the treatment of various disorders.
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PMID:[Melatonin and its role in gastrointestinal pathology]. 1946 49

Melatonin, a hormone produced by the pineal gland, has a key role in regulating circadian rhythms, most importantly, the sleep-wake cycle. Melatonin's action has led to its being tried as a treatment for a wide range of sleep disorders, such as jet lag, primary insomnia, sleep-wake cycle disruption and sleep problems in children with neuro-developmental disorders. Until recently, it had not been licensed in the UK for any indication. Prolonged-release melatonin (Circadin - Lundbeck) has now been licensed as a treatment for primary insomnia. Here we consider whether this product has a place in the management of people with this condition.
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PMID:Melatonin for primary insomnia? 1956 41

Patients with neurologic disorders commonly experience sleep dysfunction and psychiatric disorders. The most common sleep dysfunction is insomnia, which is a primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are prominent symptoms of anxiety disorders and major depression that may occur in patients who are treated but have residual sleep dysfunction. Anxiety and depressive disorders account for 40% to 50% of all cases of chronic insomnia. It is also recognized that primary insomnia and other primary sleep disorders produce symptoms that are similar to those reported by patients with psychiatric disorders. A clinician must judge whether sleep deprivation causes mood disturbance or whether depressive or anxiety disorder represents the primary reason for sleep dysfunction. When insomnia is comorbid with mild to moderate depression, therapy should begin with bedtime dosing of sedating antidepressants such as mirtazapine, nefazodone, or tricyclic antidepressants, which are preferred because of their sedative effects. Often side effects limit their usefulness. Intervention for chronic insomnia is similar in nonpsychiatric and psychiatric patients. Behavioral therapies, particularly multicomponent cognitive-behavioral therapy, and lifestyle changes show significant long-term efficacy as treatments for chronic insomnia. The most studied pharmacologic agents to treat insomnia are sedative hypnotic agents, particularly those that are active through the benzodiazepine receptor-GABA (gamma-aminobutyric acid) complex, such as benzodiazepines, eszopiclone, zaleplon, and zolpidem. Melatonin and the melatonin-receptor agonist ramelteon have not had adequate study in psychiatric patients to define their use, but small studies suggest benefit. Prescription of adjunctive trazodone (50-150 mg) is a common clinical practice to treat comorbid insomnia during antidepressant therapy, but published data are surprisingly limited, considering its frequent use. Although there has been insufficient research on the use of atypical antipsychotic agents in severe insomnia, psychiatrists use quetiapine, olanzapine, or others to lessen agitation that disrupts sleep. When insomnia or hypersomnia continue even as mood, anxiety, or thought disorders improve with standard therapy, the physician should consider the potential presence of underlying sleep disorders.
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PMID:Treatment of sleep dysfunction and psychiatric disorders. 1974 1

Sleep is a crucial biological process that is regulated through complex interactions between multiple brain regions and neuromodulators. As sleep disorders can have deleterious impacts on health and quality of life, a wide variety of pharmacotherapies have been developed to treat conditions of excessive wakefulness and excessive sleepiness. The neurotransmitter norepinephrine (NE), through its involvement in the ascending arousal system, impacts the efficacy of many wake- and sleep-promoting medications. Wake-promoting drugs such as amphetamine and modafinil increase extracellular levels of NE, enhancing transmission along the wake-promoting pathway. GABAergic sleep-promoting medications like benzodiazepines and benzodiazepine-like drugs that act more specifically on benzodiazepine receptors increase the activity of GABA, which inhibits NE transmission and the wake-promoting pathway. Melatonin and related compounds increase sleep by suppressing the activity of the neurons in the brain's circadian clock, and NE influences the synthesis of melatonin. Antihistamines block the wake-promoting effects of histamine, which shares reciprocal signaling with NE. Many antidepressants that affect the signaling of NE are also used for treatment of insomnia. Finally, adrenergic receptor antagonists that are used to treat cardiovascular disorders have considerable sedative effects. Therefore, NE, long known for its role in maintaining general arousal, is also a crucial player in sleep pharmacology. The purpose of this review is to consider the role of NE in the actions of wake- and sleep-promoting drugs within the framework of the brain arousal systems.
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PMID:Good night and good luck: norepinephrine in sleep pharmacology. 1983 4

The prevalence of insomnia in the elderly is significant. If left untreated or inappropriately treated, insomnia may contribute to increased health care resource use. Therefore, better identification and management of insomnia is required for this patient population. The etiology and magnitude of insomnia due to changes in circadian rhythms, comorbid conditions, and pharmaceutical agents are not well documented, and the utilization of over-the-counter and non-Food and Drug Administration (FDA)-approved agents to induce sleep (including antihistamines and ethyl alcohol) have not been studied in a natural setting. Evaluating the actual type of insomnia remains much more art than science for the majority of patients and providers. Another issue to consider in this population involves the relationship between patient and physician and the traditional passive patient role. Nonpharmacologic approaches (ie, cognitive behavioral therapy) for insomnia management are effective and usually are first-line therapy. However, the challenges to implementing these approaches may limit their use, thus necessitating pharmacologic therapy. There are currently 3 FDA-approved drug classes for the treatment of insomnia: benzodiazepines, benzodiazepine receptor agonists, and melatonin receptor agonists. Although all agents in these classes are efficacious, benzodiazepines and benzodiazepine receptor agonists are associated with adverse events that must be considered when treating insomnia in the elderly. Melatonin agonists have a mechanism of action that regulates normal sleep-wake cycles and readjusts circadian rhythms, which may confer a better safety profile than traditional sedative-hypnotics that target gamma-aminobutyric acid receptors. Because the 3 currently approved drug classes for insomnia have similar efficacy, safety considerations should be of paramount importance for the elderly patient; however, additional data are needed to appropriately assess the risk-benefit ratios of each.
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PMID:Review of insomnia pharmacotherapy options for the elderly: implications for managed care. 2003 57

Behavioral measures, eg, exercise and improved sleep hygiene, can enhance sleep quality and combat insomnia and excessive sleepiness (ES) in shift workers and individuals with shift-work disorder (SWD). Napping before a shift followed by consumption of a caffeinated drink and, if appropriate, scheduled naps at work, may improve ES in patients with SWD. Use of bright light therapy to partially re-entrain the circadian clock should be explored for all night-shift workers-particularly those with SWD. The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD. Alongside nonpharmacologic interventions, they can be included in a comprehensive management plan for SWD. Melatonin or other sleep-promoting agents may help shift workers achieve sleep during required rest periods and when adjusting to night-shift work; studies are needed in patients with SWD to better evaluate the utility of these agents in this population.
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PMID:Managing the patient with shift-work disorder. 2007 7

Insomnia is the predominant sleep concern in children with autistic spectrum disorder (ASD), and its nature is most likely multifactorial, with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors involved. Children with ASD experience sleep problems similar to those of typically developing children, although the prevalence is markedly higher, occurring in 44-83% of school-aged children with ASD. Caregivers usually report that insomnia is the most frequent sleep disorder, described as disorders of initiating and maintaining sleep, restless sleep, bedtime resistance, co-sleeping, alterations of sleep hygiene, and early awakenings in the morning. Many actigraphic studies have added information on sleep disorders, confirming the questionnaire findings in the majority of cases. There are relatively few polysomnographic data for ASD, compared with questionnaire studies, and most of these studies reported a reduction in total sleep time and more undifferentiated sleep in the youngest patients. These findings were associated with several sleep microstructure alterations during rapid eye movement (REM) sleep, and with non-REM (NREM) sleep microstructure changes that appeared to be related to cognitive impairment rather than to the autistic core. Moreover, few data about other less frequent sleep disorders, such as periodic limb movements disorder and obstructive sleep apnea syndrome, bruxism, and the influence of epilepsy and EEG abnormalities, are available. Both pharmacologic and behavioral interventions have been suggested for the treatment of sleep problems in autistic children. The most common types of behavioral interventions are complete extinction (removing reinforcement to reduce a behavior) and various forms of graduated extinction. Melatonin has shown promising results in the treatment of insomnia in children with ASD. Although controlled studies are limited, there are more data demonstrating the safety and effectiveness of melatonin in ASD than for other sedative/hypnotic drugs. Finally, a dual treatment for insomnia in ASDs with melatonin and behavioral techniques has been suggested. A recent study using a combination of genetic and functional experimental techniques reported evidence that low melatonin concentration caused by a primary deficit in acetylserotonin methyltransferase activity is a risk factor for ASD. Sleep problems usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Further studies, beginning at younger ages, are necessary to better investigate these aspects and the role of melatonin in insomnia in children with ASD.
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PMID:Epidemiology and management of insomnia in children with autistic spectrum disorders. 2021 44


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