Insomnia sleep disorders

Insomnia Sleep disorder that involves difficulty falling or staying asleep, or sleep that is not refreshing defined as transient if it occurs for less than one week, acute if it lasts one week to one month, and chronic if it lasts more than one month. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

Describe the mechanisms of the sleep disorders covered in this chapter, including insomnia, narcolepsy, restless-legs syndrome, obstructive sleep apnea, and parasomnias. 

To determine the success of treatment, evaluate whether the treatment plan restored normal sleep patterns, reduced daytime sequelae, and improved quality of life without causing adverse effects. Schedule patients for follow-up within 3 weeks for insomnia and within 3 months for other sleep disorders. Perform a detailed clinical history to determine the patient s perception of treatment progress and symptoms along with medication effectiveness and side effects. 

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

The patient experiences anxiety, apathy, bradyphrenia (slowness of thought processes), confusional state, dementia, depression, hallucinosis/psychosis (typically drug-induced), and sleep disorders (excessive daytime sleepiness, insomnia, obstructive sleep apnea, and rapid eye movement sleep behavior disorder). 

Subsequent to the extensive medicinal chemistry exploration of Orexin antagonism, its utility in the treatment of sleep disorders in man has been reported recently. This important milestone for the therapeutic validation of the target results from the 0X1 /OX2 receptor antagonist ACT-078573 (20) [57], SB-649868 has also been announced to be in phase II clinical development, but neither the structural formula nor the results have been reported to date [58,59]. Moreover, insomnia treatments based on orexin modulation may be addressed by not only receptor antagonism but by inhibition of pathways related to the genesis of the bioactive peptides Orexin A or B, e.g. inhibition of Orexin-converting enzyme [60]. 

NIH State-of-the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults (ed. NIH, National Heart, Lung and Blood Institute, National Center on Sleep Disorders Research), 2005. 

Poor Timing of Neurotransmission. The activity of some brain circuits, like the secretion of certain hormones, varies at certain times of the day. Called circadian rhythms, the timing of these rhythms may be disrupted in some illnesses. Examples include sleep disorders such as insomnia and narcolepsy, as well as other conditions such as nighttime binge-eating disorder. 

The sleep disorders fall into four main categories (1) insomnia, (2) hypersomnia, (3) parasomnias, and (4) sleep schedule disorders. Insomnia is the most common sleep problem. It is simply defined as poor sleep and can be manifested by difficulty falling asleep, difficulty staying asleep, waking up too early, or waking up in the morning without feeling refreshed. 

Although we are focusing on the primary sleep disorders, sleep disturbance quite often occurs as a symptom of another illness. Depression, anxiety, and substance abuse can impair the quality of sleep, though in the setting of chronic insomnia, other psychiatric disorders account for less than 50% of cases. Nightmares are a frequent complication of post-traumatic stress disorder (PTSD), and pain, endocrine conditions, and a host of medical illnesses can produce sleep problems. Thus, when discussing insomnia or hypersomnia, we are well advised to remember that these can be either a symptom of a psychiatric syndrome, a medical illness, or a sleep disorder. 

In this chapter, we will not attempt to provide an exhaustive description of every sleep disorder. Medication therapy plays a minimal role in the treatment of many sleep disorders. In fact, we contend that medication, apart from being an integral component of a comprehensive multimodal treatment program, is seldom an effective treatment for any sleep problem with the possible exception of acute insomnia due to an identifiable and short-lived stressor. Nevertheless, medications do play a part in the treatment of some sleep disorders. 

The discussion that follows will be limited to those sleep disorders that are common in adults and that frequently require medication as part of the usual treatment. Specifically, we will discuss insomnia and narcolepsy (the most common hypersomnia). We will briefly mention treatments for the nighttime limb movement disorders. 

It is important that the breathing-related sleep disorders be distinguished from other forms of insomnia. The key reason is that many of the most common medications used to treat insomnia worsen the breathing-related sleep disorders. For example, benzodiazepines, the most commonly used class of sleeping pills, can... 

Sleep disorder Rebound sleep disorder, which is characterized by recurrence of insomnia to levels worse than before treatment began, may occur following abrupt withdrawal of triazolam, usually during the first 1 to 3 nights. Gradual rather than abrupt discontinuation of the drug may help avoid this syndrome. 

The International Classification of Sleep Disorders lists 88 types, with insomnia the most prominent symptom for many of these (17). Chronic insomnia is the most common sleep problem for which patients consult practitioners (18) and usually reflects psychological/ behavioral disturbances ( 19). Differences in treatment recommendations support the distinction between DSM-IV and the International Classification for Sleep Disorders ( 20). The DSM-IV divides primary disorders into two major groups the dyssomnias (in which the predominant disturbance is the amount, quality, or timing of sleep) and the parasomnias (in which the predominant disturbance is an abnormal event occurring during sleep) (7). 

Acute anxiety states panic attacks generalized anxiety disorder insomnia and other sleep disorders relaxation of skeletal muscle anesthesia (adjunctive) seizure disorders... 

Ramelteon Activates and MT2 receptors in suprachiasmatic nuclei in the CNS Rapid onset of sleep with minimal rebound insomnia or withdrawal symptoms Sleep disorders, especially those characterized by difficulty in falling asleep not a controlled substance Oral activity forms active metabolite via CYP1A2 Toxicity Dizziness fatigue endocrine changes Interactions Fluvoxamine inhibits metabolism... 

Melatonin has been studied in the treatment of various sleep disorders, including insomnia and delayed sleep-phase syndrome. It has been reported to improve sleep onset, duration, and quality when administered to healthy volunteers, suggesting a pharmacologic hypnotic effect. Melatonin has also been shown to increase rapid-eye-movement (REM) sleep. These observations have been applied to the development of ramel-teon, a prescription hypnotic, which is an agonist at melatonin receptors (see Chapter 22). 

The brain and its infinite complexity will surely puzzle us for centuries to come. But, as with any other organ in the body, things can go wrong with the brain (and the behavior it controls). Whether it is Alzheimer s or Parkinson s disease, anxiety, depression, or schizophrenia, there is no shortage of possible diseases and disorders of the brain. And sleep, which the brain closely controls and monitors, is also susceptible to going out of whack. In recent decades, with the advancement of sleep research and improved knowledge about sleep, scientists and medical doctors have come to realize that sleep disorders are much more common than anyone previously imagined. In this chapter, we discuss some of the more common sleep disorders, such as insomnia and sleep apnea, as well as more rare disorders like narcolepsy and REM behavior disorder. 

Insomnia is, by far, the most common sleep disorder it is estimated that approximately half of adults experience some form of insomnia at least once in their lives. Insomnia is less common in children and teenagers than in adults, but it is particularly prevalent in elderly people, as their sleep becomes fragmented with age. Insomnia is slightly more common in females than males. 

Since animals sleep, this begs the question—do animals have sleep disorders Well, we may never know if animals suffer from insomnia because we can t ask them, Are you getting enough sleep But in fact, there are several species of animals that display behaviors remarkably similar to symptoms of human sleep disorders. For example, pigs can show signs of sleep apnea and have been used to study potential treatments for the disorder. 

Insomnia is a complaint, not a disease. The causes of insomnia are classified both in the DSM-IV for psychiatrists and in the International Classification of Sleep Disorders for sleep experts (Table 8—3). Insomnia can be a primary problem, or it can be secondary to medical or psychiatric disorders or to medications. Insomnia can also be due psychophysiological factors such as stress or to circadian rhythm distur-... 

Insomnia secondary to a general medical condition, especially with pain- or sleep-disordered breathing Circadian rhythm disturbance Periodic limb movement disorder Restless legs syndrome... 

To review a clinical description of insomnia and sleep disorders. 

The time spent reviewing insomnia and sleep disorders was just right. ... 

The primary drug therapies are psychostimulants which are indicated for both emotional based sleep disorders (i.e., narcolepsy) as well as ADHD. The drugs of choice are Ritalin (methylphenidate), dextroamphetamine or Cylert (pemoline), all CNS stimulants that effect the monoamine systems. The current therapies provide symptomatic relief but the current medications are not without side effects, including abuse potential, cardiovascular effects, insomnia, appetite suppression, head and stomach aches, crying and nervous mannerisms. 

GHB (gamma hydroxybutyrate) was originally developed as an anesthetic, but was withdrawn due to unwanted side effects. GHB holds several U.S. patents for use in the treatment of sleep disorders such as narcolepsy and insomnia, and as a muscle relaxant. GHB is used as a fast-acting anesthetic in small animals. The compounds and compositions made from GHB are useful in the treatment of Parkinson s disease, schizophrenia, and other dopamine-related disorders. 

Researchers used to think that older adults produced very little melatonin. Since the elderly tend to have more problems with insomnia and other sleeping disorders, scientists hypothesized that these lower levels of melatonin were the cause of sleeping problems in this population. 

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