Insomnia Holistic Treatments

Natural Insomnia Program

The Insomnia Exercise Program is a simple audio program that works to Train Your Brain to switch from normal, fast-paced brain waves to slow, delta and theta waves and put you to sleep mind and body naturally. This is a 2-part program. Part 1 is a 25 minute audio where I lead you step by step to reach those slow theta and delta stages that knock you out in a deepest sleep of your life. This is done through a combination of mind, eye and relaxation exercises. Part 2 is a 50 minute audio of sound therapy where you hear the relaxing sound that draws you into the wonderful land of dreaming. After youve listened to the audio a few times, youll most likely be sound asleep long before it even comes to this part but it is important because it will draw you into deeper and deeper sleep so you dont wake up after a few minutes and not be able to doze off again. All you have to do is listen to the audio in your bed and get ready to fall asleep! Read more...

Natural Insomnia Program Summary

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Melatonin Agonists for the Treatment of Sleep Disorders and Major Depression

Melatonin receptors 26 2.2. Regulation of melatonin receptors 27 2.3. Melatonin and sleep 27 2.4. Melatonin and depression 28 3. Synthetic melatonin agonists 28 3.1. Indolic melatonin agonists 29 3.2. Structurally diverse synthetic melatonin agonists 30

Regulation of melatonin receptors

Desensitization and down regulation of GPCRs by agonist ligands may effect the physiological responses mediated by the particular GPCR. The regulation of melatonin receptors by agonists has been studied in an effort to understand the mechanism regulating receptor expression. Desensitization of MT1 receptors by melatonin requires prolonged exposure and is not accompanied by significant observable receptor internalization 29 . Instead, a slight but significant desensitization of melatonin-induced GTPgS binding was revealed. Exposure of recombinant MT2 receptors to melatonin, however, leads to a rapid down-regulation of specific 125I-melatonin binding and correlates with desensitization of MT2 receptor function 30 . The authors suggest that administration of high doses of MT2 agonists may desensitize the MT2 receptor and impair melatonin-induced phase shifts in circadian rhythms or reduce melatonin-induced vasodilation.

Melatonin and depression

Melatonin has been described in the literature as having an antidepressant effect in some animal models of depression. In the mouse tail suspension test (TST), the antidepressant activity of melatonin was proposed to be mediated through an interaction with NMDA receptors and the l-arginine-NO pathway 44 . In a rodent behavioral despair model, administration of melatonin decreased the immobility time that was observed on chronic exposure to forced swimming test 45,46 . Daily treatment of chronically stressed mice with melatonin was shown to reverse various perturbations induced by stress 47 . Recently, published results monitoring the levels of melatonin in trout, also seem to indicate it plays a role in the regulation of stress and anxiety 48 .

Indolic melatonin agonists

Melatonin has been studied extensively as described above and many close indole containing analogs have also been reported in the literature. The melatonin agonist LY-156735,2 was recently reported to alleviate the symptoms of shift lag and to help resynchronize circadian rhythms at a dose of 5 mg day in human clinical trials 53 . Indole derivative 3, with 5-fold greater potency than melatonin was recently described 57 . The group also reported the synthesis and biological evaluation of tricyclic melatonin analogs with alkyl and cycloalkyl groups in the beta position of the ethylamido chain 58 . When two beta methyl groups were added to the side-chain of the methoxyl-substituted ligand, 4 an increase in agonist potency was observed. However, more bulky R group beta-substituents, reportedly led to antagonism. Recently sulfur analogs of melatonin, 5 and 6 were reported to have decreased binding affinity at human MT1 and MT2 receptors combined with reduced potency as melatonin agonists...

Recent Advances in the Treatment of Insomnia

Melatonin Receptor Agonists 68 3.2 MLT agonists in clinical development for insomnia 69 Insomnia is defined as a condition of unsatisfactory quantity and or quality of sleep, which persists for a considerable period of time, including difficulty in falling asleep, difficulty in staying asleep, or early final wakening 1 . Insomnia is the most common sleep complaint within the sleep disorders and is classified by the duration of the problem as well as the underlying pathophysiology. According to duration, it is considered transient (less than 4 weeks), short term (from 4 weeks to 3-6 months) and chronic (more than 6 months 2 but new trends consider chronic insomnia more than 30 days 3 ). Insomnia is also named primary when is a condition per se and secondary when is arising as a symptom of a comorbid disorder. Disease prevalence ranges from 5 to 35 of the adult population, with variations reported depending on the methods used in epidemiological studies 4 . Insomnia in the pediatric...

MLT agonists in clinical development for insomnia

Compound 12 (LY-156735 PD-6735) is a melatonin MT1 and MT2 agonist currently undergoing phase II trials for the improvement of sleep onset latency in patients with primary insomnia. In 2001, the compound was assigned orphan drug status for the treatment of circadian rhythm sleep disorders in blind patients with no light perception. The compound has been shown to be safe and well tolerated. In addition, it dose-dependently reduces objective polysomnographic sleep parameters without producing any morning-after psychomotor impairment, as well as reducing the subjective time to fall asleep in patients with moderate to severe primary insomnia 32-37 . 12 demonstrated chronobiotic efficacy in healthy volunteers undergoing simulated shift lag 38 and showed adequate pharmacokinetics, pharmacodynamics and safety at doses of 20-40 mg in healthy volunteers 39 . VEC-162 is a dual MT1 MT2 melatonin agonist in phase II trials (no structure disclosed). A study in 39 subjects revealed that the...

Ramelteon Insomnia [7378

Unlike most treatments of insomnia that target the GABA (g-aminobutyric acid) receptor complex, ramelteon is an agonist of the melatonin receptor. In particular, it has high selectivity for the MT1 and MT2 subtypes, which have been implicated in the maintenance of circadian rhythms, over the MT3 receptor responsible for other melatonin functions. Its lack of affinity for not only the GABA receptor complex but also neurotransmitter, dopaminerigic, opiate, and benzodiazepine receptors suggests an improved safety profile devoid of the abuse potential of the hypnotic drugs that target these receptors. As such, ramelteon is not a scheduled drug. The development of ramelteon has come from a concerted effort to elucidate longer half-lived versions of the endogeneous ligand melatonin with improved oral bioavailability and selectivity. By incorporating the methoxy moiety of melatonin into a conformationally constrained indeno 5,4-b furan, the oxygen is locked into an orientation that is...

Ionotropic Gaba Receptors And Sleep Disorders

The treatment of insomnia is regarded as a developing market for agents acting on GABAA and possibly GABAc receptors. GABA systems are known to play an important Oleamide is inactive in (33 knockout mice and a mutation in (33 GABAA receptor subunits has been described in a patient with chronic insomnia 39 . Oleamide and related compounds are being intensively investigated for use in sleep therapy 40 . Indiplon 9 acts in a similarly selective manner to oleamide and is in clinical trials for the treatment of insomnia 41,42 . Also in clinical trials for the treatment of sleep disorders is THIP 4, a directly acting GABAA receptor partial agonist that interacts with a GABAA receptor population that is insensitive to benzodiazepines, zolpidem, zaleplon and indiplon 43 . THIP is a moderately potent GABAc receptor antagonist 29 . Unlike GABA, THIP passes the blood-brain barrier on systemic administration and is a potent analgesic 44 . The side effects of THIP (including sedation, dizziness,...

Synthetic Melatonin Agonists

Melatonin from the pineal gland was recently reported to be distributed to the brain via the cerebrospinal fluid 49 . Exogenously administered deuterated melatonin has low absolute bioavailability in man (1-37 ) due to first pass metabolism and a short half life reported to be approximately 40 min 50 . The shortcomings of exogenously administered melatonin as a drug have led to the search for improved synthetic melatonin agonists. Some of the novel synthetic melatonin agonists previously reported in the literature include agomelatine (S 20098), ramelteon (TAK-375), LY-156735, GR196429, and BMS-214778 51-55 . The efficacy of novel melatonin agonists in human sleep regulation and the treatment of depression has been well documented and is described in more detail for the specific ligands below 51-53 . The role of melatonin agonists in the treatment of anxiety is less clearly defined, however, some recently published results in anxiolytic animal models seem to indicate they play a...

Biology Of Melatonin

The hormone melatonin 1 (N-acetyl-5-methoxytryptamine) is produced and secreted from the pinealocytes of the pineal gland 1 . Melatonin is synthesized in a circadian mode as it is produced at high levels at night and low levels during the day. The suprachiasmatic nucleus (SCN) of the hypothalamus, which is considered the master clock, regulates the rhythmic secretion of melatonin. Melatonin, in turn, interacts at receptors in the SCN to suppress neuronal firing. The ability of melatonin to shift the circadian rhythm, modulate the sleep-wake cycle and circannual rhythms in many species, including man, is well documented as detailed in the recent literature 2-8 . Numerous recently published articles have also described the effect of melatonin on phase shifts, for example those associated with shift work or jet lag 9-13 . Other effects of melatonin described in the literature include its neuroprotective, antiinflammatory, pain modulatory, retinal, vascular and antioxidant properties...

Melatonin receptors

Melatonin has high affinity for two G-protein coupled receptors (GPCRs), designated MT1 and MT2, and activates the inhibition of adenylyl cyclase via these receptors 21 . Melatonin receptors MT1 and MT2 have amino acid sequences which are 60 identical. In situ analysis has revealed that MT1 mRNA is present in human SCN. Autoradiographic localization studies have shown that 125I-melatonin binding is present in the SCN of most mammalian species including human. MT2 mRNA is not as abundant as MT1 and has been found in SCN and retina by RT-PCR 22 . Most species, with the exception of humans, show specific 125I-melatonin binding in the pars tuberalis of the pituitary. Pituitary melatonin receptors are believed to contribute to the regulation of seasonal changes in reproductive function 7 . The distinct function of MT1 and MT2 has yet to be clearly defined, however, their role in the regulation of sleep and in circadian rhythm is well established 22 . In mice lacking the MT1 receptor,...

Melatonin and sleep

Sleep deprivation and poor sleep quality can reduce cognitive function, memory and negatively affect mood 31,32 . Understanding the relationship of melatonin levels to sleep disorders, depression and anxiety has become a topic of considerable recent research and the melatonin receptors MT1 and MT2 have emerged as therapeutic targets of interest 33 . Melatonin's effect on the duration and quality of sleep has been reported in the literature and in a recent clinical trial, the effects of exogenous melatonin on disturbed REM sleep in humans was studied 34,35 . The results showed that melatonin was significantly more effective than placebo in measures of sleep parameters with patients on melatonin experiencing significant increases in REM sleep percentage and improvements in subjective measures of daytime function 35 . Melatonin therapy could be a useful treatment for sleep disorders associated with shift work or patients with reduced melatonin levels. Age-related reduction in serum...

ALT See alanine aminotransferase

Amantadine 1-Adamantanamine hydrochlo-ride. A primary symmetrical amine with limited prophylactic activity. Effective (about 70 ) against Influenza virus A but not against Influenza virus B, C nor Measles. Amantadine-resistant influenza virus mutants are readily isolated. The drug does not inhibit viral attachment but acts at an early stage by blocking the function of the influenza M2 protein. It may cause some mental disturbance in patients with a history of psychiatric disorder. Drowsiness, slurred speech, lethargy, dizziness and insomnia are side-effects. The a-methyl derivative, rimantadine, reportedly produces fewer side-effects. See rimantadine hydrochloride.

HT2C receptor modulators

5-HT2C antagonists may also have a role in the treatment of depression. It has been shown that the 5-HT2C antagonists SB-242084 and RS 102221 potentiate the action of the SSRI citalopram on rat cortical and hippocampal 5-HT levels, although the 5-HT2C antagonists alone had no effect 31 . It has also been claimed that the clinical antidepressant efficacy of agomelatine, a melatonin agonist, may be in part due to 5-HT2C antagonism 32 .

HT7 receptor antagonists

The 5-HT7 receptor has been postulated to play a role in depression based partly on its distribution in the brain and also on the observation that chronic treatment with antidepressants results in downregulation of this receptor. Additional support for this hypothesis has been gained by a recent study showing that 5-HT7 receptor knockout mice demonstrate antidepressant-like profiles in forced swim and tail suspension tests 33 . The identification of selective antagonist tool compounds has helped add further evidence in support of the hypothesis. For example, SB-269970, 16, exhibits antidepressant-like activity, even though this compound has a rather poor PK profile. SB-656104-A, 17, has been identified as a 5-HT7 antagonist with better PK properties and has been shown to modulate REM sleep in rats in a manner consistent with potential antidepressant-like activity 34 .

Maintaining a Healthy Weight

Being overweight is a major health problem in the United States, and there are many good reasons to keep your weight within a healthy range. You will feel better, look better, and have more energy than men who are overweight. Having more energy makes you more likely to exercise, which can help you fall asleep faster and sleep more restfully. But the most important reason to keep your weight within a healthy range is that you will lower your risk for certain chronic diseases, including heart disease, high blood pressure, diabetes, and certain forms of cancer. Doctors no longer believe that it is acceptable to gain a few pounds as you age. Maintaining your weight at a reasonable level throughout your life is key when it comes to reducing your risk for disease.

Zidovudine And Dideoxynucleoside Analogues As Antiretrovirus Drugs

Within 2 years of the isolation of the AIDS virus a series of promising antiviral compounds had been discovered and zidovudine had been shown to be effective in prolonging the life of AIDS patients. The drug is rapidly absorbed after oral administration with a short 1 hour half-life and so the drug is given two or three times daily. The first double-blind placebo-controlled trial of zidovudine in AIDS patients had to be stopped and the code broken when it was found that virus induced lethality in the zidovudine-treated group was only one compared with 19 in the control group of approximately 194 patients. In addition, fewer opportunistic infections developed in the zidovudine-treated group, and a reduction in the level of circulating viral p24 core antigen indicated a specific antiviral effect of the compound. Zidovudine is now considered to be useful for prolonging the life of these patients for up to 1 year, but its use is enhanced by drug combinations. The original severe problems...

GABAa receptor modulators

GABAa receptor agonists used for insomnia fall into two classes 'Z-drugs' and benzodiazepines. Zolpidem, a 'Z-drug', is the market leading compound in this therapeutic group and will enter the generic market in 2007. This fact has triggered the search for alternatives with improved properties, e.g. increased duration of action or elimination of day-after and rebound effects. The search strategies fall into three main categories innovative formulations and devices for older compounds, enantiomerically pure molecules and alternative structures. We have attempted here to review the strategies to improve 'Z-drugs' together with the recent medicinal chemistry advances in this area and the pharmacological and clinical outcome, taking into consideration that the pharmacology of GABA receptors and their therapeutic relevance has been recently reviewed by M. Chebib et al. in this series 13 .

Event Type Ambulatory Cassette Recording

Eventually, this loop concept was closed by including output software that reassembled the delayed EEG into the multiplexed format for transmission to another demultiplexing unit that was coupled to a Mingograph EEG machine. If a clinical event occurred, the activation of the seizure button caused it to be permanently stored on the computer tape. It also signaled the EEG machine to write out the two minutes of delayed EEG leading up to the event. The EEG machine was also programmed to take regular samples during the night in order to capture the natural sleep of the patient. 25

Nonbenzodiazepine hypnotics Zdrugs

'Z-drugs' are the most frequent treatment for insomnia with the compounds zolpidem, zaleplon and zopiclone marketed for transient insomnia and eszopi-clone (S-isomer of zopiclone) for both transient and chronic insomnia. These non-benzodiazepine structures display efficacy equivalent to benzodiazepines for insomnia. The half-lives, ranging from 1.5 to 5 h, are claimed to be enough for sleep maintenance and to avoid daytime sedation. Moreover, 'Z-drugs' have a reduced propensity for inducing tolerance, withdrawal and abuse compared to benzo-diazepines 14 . However, like benzodiazepines, they are classified as schedule IV drugs by the Drug Enforcement Administration (DEA). Eszopiclone, the latest approved 'Z-drug', in a 6-month study in patients with chronic insomnia and following studies to 12 months, demonstrated significant decrease of sleep latency and awakenings and improvement in total sleep time. Importantly, daytime function and alertness were not affected, nor was there...

Recent advances in Zdrugs research

Imidazo 1,2-a pyridine, the central scaffold in Zolpidem (1), has been extensively explored in the search for insomnia drugs. Fang et al. 17 have described compounds bearing such heterocycles but lacking the side chain amide group. 2 inhibits 3H -flunitrazepam binding to central receptors with an IC50 value of 36 nM and to peripheral receptors with an IC50 of 180 nM. In vivo, this compound was active at 10mg kg in the maze test for anxiety 17 . In addition, Falco et al. have described compounds bearing an inverse amide group side chain (3) that display sedative-hypnotic action (94 inhibition of motor activity) following i.p. administration in mice 18 . Azaisosteres of zolpidem, pyrazolo 1,5-a pyrimidines, have been identified as selective ligands for Bz GABAA receptor subtypes. Compound 4 has been described to have affinity only for a1 p2y2 subtype (Kj 31 nM) and revealed sedative and anxiolytic-like properties without any amnesic and myorelaxant effects in rodents 19 .

Other GABAa receptor modulators

Gaboxadol (9) is a selective extrasynaptic GABA receptor agonist in late-stage investigation for the treatment of insomnia. The action of this compound was extensively reviewed in Chebib et al. 13 and updated in Wafford et al. 23 . Nevertheless, the sponsor companies Merck & Co., Inc., and H. Lundbeck A S announced in March 2007 that the results from recently completed clinical studies do not support further development and announced the discontinuation of their joint development program for gaboxadol. Tiagabine (10), a GABA reuptake inhibitor launched for epilepsy, is undergoing clinical trials for insomnia. Tiagabine 4, 6 and 8 mg significantly increased slow-wave sleep, with a significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events 24 . A phase II study of EVT-201, a partial positive modulator of GABAA...

Histamine receptor modulators

Based on the well-known sedative effects of histamine H1 receptor antagonists 94 , three compounds have advanced to clinical development Doxepin, HY-2901 and NBI-75043. Doxepin (37), a mixed H1 H2 receptor antagonist, has completed a successful phase III program for the treatment of insomnia. Doses of 3 and 6mg in elderly adults with primary insomnia were associated with significant and dose-dependent improvements in sleep maintenance, duration and onset 95 . The doxepin analogue, HY-2901 (38), has been shown to have high affinity for histamine H1 receptors (Ki 69.5 nM) and to dose-dependently prolong non-REM sleep in rats (0.3-30 mg kg). Regarding NBI-75043, this compound is the most recent H1 receptor antagonist entering phase I clinical development for insomnia, but neither the structure nor preliminary results have yet been disclosed.

Diagnosis of Epilepsy

Some paroxysmal clinical episodes are associated with clear electrographic seizures, helping to make the diagnosis. The absence of epileptiform EEG abnormalities at the time of paroxysmal behavioral disturbances increases the likelihood that the events are not epileptic, but rather manifestations of other illnesses. Two other groups of illnesses produce symptoms similar to those of seizures. There are events of other physiologic bases such as cardiac arrhythmias causing syncope, episodes caused by cerebrovascular disease, movement disorders, and unusual manifestations of sleep disorders. There are also events of psychiatric origin. Taken together, all of these events are generally referred to as nonepileptic seizures. All of these can produce bizarre and unusual movements and behavior with some resemblance to epileptic seizures.

Epidemiology And Implications Of Neuropsychiatric Features In Parkinsonian Disorders

What are the clinical implications of neuropsychiatric symptoms in patients with parkinsonian disorders Again, most research has been performed on patients with PD, and it seems reasonable to extrapolate the findings from these studies to patients with atypical parkinsonian disorders. First, several studies have consistently demonstrated that neuropsychiatric symptoms have strong negative influences on the quality of life, including physical, social, and psychological well-being of patients with PD, even after controlling for motor, functional, and cognitive disturbances. For instance, depression has consistently, and irrespective of instruments used to assess depression, been found to be among the most important independent predictors of impaired quality of life in PD patients (29-31), and a longitudinal study reported that depression and insomnia were the most important factors associated with poor quality of life (32). Although there is overlap between the symptoms of depression...

Psychiatric Aspects Of Dementia With Lewy Bodies

Sleep disturbances, such as insomnia and increased daytime sleepiness, are more common in DLB than AD (62), and are also pronounced in PD (63). REM sleep behavior disorder (RBD) is character ized by loss of normal skeletal muscle atonia during REM sleep with prominent motor activity and dreaming. RBD is particularly common in DLB (64). When associated with dementia or parkin-sonism, RBD usually predicts an underlying synucleinopathy, and it has been proposed that RBD should be included in the clinical diagnostic criteria for DLB (64). In PD, an association between RBD and visual hallucinations has been reported (65). Interestingly, during clonazepam treatment, which may improve RBD, the frequency of visual hallucinations decreased, suggesting a causal link between RBD and halucinations (65).

Pharmacological Treatment Of

A variety of other psychotropic drugs are used in the short-term clinical management of DLB. Anxiety and insomnia are common symptoms that may respond well to benzodiazepine sedatives and antidepressant, and anticonvulsants may be useful in controlling behavioral and psychotic symptoms. Most of these observations are based upon clinical experience and anecdote, rather than evidence and given the poor tolerability of DLB patients to psychotropic drugs, it is probably best to avoid all pharmacological interventions with psychotropic agents other than cholinesterase inhibitors, unless the clinical situation makes it imperative. Given the potential adverse response to neuroleptics, studies evaluating the potential value of nonpharmacological treatment approaches are

Managing Work While Nurturing Relationships

Close monitoring virtually every moment often quick interventions were needed to protect him from unanticipated dangers. In addition, like many children with ADHD, her son had chronic difficulty falling asleep. This resulted in his making numerous curtain calls well past his bedtime often it also brought two or three interruptions to her sleep each night as she was asked to calm him after a nightmare or to change wet sheets on his bed. I'm usually doing OK at getting them the basics, but I know that I'm just not there enough for them emotionally. I'm always disorganized and frazzled and tired and too frustrated. Half the time when I lie down beside them at night to read a story, I fall asleep before they do and during the day, so much of the time I'm just too impatient. I'm not expecting to give perfection no parent can do that. But I know they need me to be there to talk with them and to listen, to explain things to them, and to be there for them emotionally. I want to do that for...

The Clinical Interview The Most Sensitive Assessment Tool

Usually such an interview requires at least two hours, during which time the interviewer and patient will discuss the patient's (1) adaptive strengths and weaknesses, how the person does their work, what they do for fun, and what they struggle with daily (2) strengths and stressors in the family background as well as any blood relatives with related problems (3) health history, focusing on any medical or developmental problems that may be relevant (4) history of school achievement and struggles with particular types of academic work (5) relationships with peers, family, teachers, employers, and friends (6) eating and sleeping habits (7) current mood patterns and any significant difficulties with anxiety, temper, or behavior and (8) history of previous evaluations or treatment.

Two cholinergic systems their connections and related issues

Thalamocortical and cortical neurons. Activation is defined as a state of membrane polarization which brings thalamic and cortical neurons closer to their firing threshold, thus ensuring safe synaptic transmission and quick responses to either external stimuli during waking or internal drives during REM sleep (Steriade, 1991). Moreover, although the emphasis was placed since the 1980s on cholinergic neurons, in order to specify chemically-coded systems within a structure prior viewed as 'non-specific', non-cholinergic neurons are much more numerous than the cholinergic ones in the brainstem reticular core and most of them, especially the large-sized ones, are glutamatergic (Jones, 2000). In the upper midbrain reticular formation, where there are virtually no cholinergic neurons, cells with antidromically identified projections to the thalamus display precursor signs of increased activity during shifts from slow-wave sleep to either wakefulness or REM sleep (Steriade et al., 1982), and...

Traditional Medical Practitioners

Antimicrobials are often perceived as 'strong' medicine, capable of curing almost any kind of disease. In their classic study in West Africa, Bledsoe and Goubaud (1985) reported that people had specific criteria for selecting medicines. Colour is an important factor that determines perceived efficacy. Multicoloured capsules are believed to be particularly effective because the different colours imply that several kinds of medicine have been combined to make a very powerful drug. A secondary school graduate reported that he took a 'red and black' capsule, the antimicrobial ampicillin, after a hard day's work on the farm, to treat the sore body and to wake up refreshed for another day (Bledsoe and Goubaud 1985).

Mitochondrial Damage in Traumatic CNS Injury

During World War II (WWII) the British army banned the SS terminology in hopes of avoiding another epidemic of these cases, which they may or may not have viewed as physical disorders. However, with the start of the war it became readily apparent that disavowing the existence of this disorder did not prevent another epidemic. In response to the army regulations regarding this disorder, alternative terminology arose in its place, such as post-concussion syndrome (PS) or post-trauma concussion state (coined by Shaller). Eventually, physicians began to realize that many of the soldiers that suffered from this concussed state had been in close proximity of an explosion during battle. This led them to speculate that some force, that had no perceptible outward affect on the body, had a substantial effect on fragile neural tissues. In an attempt to, once again, clarify the etiology of this disorder, Denny-Brown suggested that it was the timeline of symptom presentation within the individual...

Anesthesia and the cholinergic system implications from sleep research

A host of central neurotransmitter systems subserving GABAergic, glutamatergic, adrenergic, seroto-nergic and cholinergic transmission are likely affected by anesthetics (Angel, 1993). The effect of anesthetics on cholinergic transmission has been recently reviewed (Lydic and Baghdoyan, 1997 Durieux, 1996 Yamakura et al., 2000 Tassonyi et al., 2002) and it is suggested that alteration of central cholinergic transmission is involved in mediating several effects including sedation and loss of consciousness. Compelling evidence for this suggestion derives from studies on sleep awake states (Steriade, 1999). Early animal studies demonstrated that acetylcholine (ACh) content of the whole brain varies as a function of arousal (Richter and Crossland, 1949), cortical ACh release changes in phase with the sleep awake cycle (Celesia and Jasper, 1966), and anesthetics suppress EEG activation and reduce cortical ACh release (Mitchell 1963). In addition, intravenous administration of...

Microdialysis studies of acetylcholine

Schematic representation of the microdialysis data showing changes in acetylcholine levels during different stages of waking and sleep. During active waking (exploration), animals have higher levels of acetylcholine than during quiet waking (immobility, eating, grooming). Acetylcholine levels fall to 1 3 of waking levels during slow wave sleep, but rise to levels above active waking during REM sleep (based on Jasper and Tessier, 1971 Kametani and Kawamura, 1990 Marrosu et al., 1995). Fig. 1. Schematic representation of the microdialysis data showing changes in acetylcholine levels during different stages of waking and sleep. During active waking (exploration), animals have higher levels of acetylcholine than during quiet waking (immobility, eating, grooming). Acetylcholine levels fall to 1 3 of waking levels during slow wave sleep, but rise to levels above active waking during REM sleep (based on Jasper and Tessier, 1971 Kametani and Kawamura, 1990 Marrosu et al., 1995).

Disorders of Arousal and Motivation

Charles was not depressed in the sense of being immobilized by profound sadness or by a severe lack of energy. He was able to get out of bed and attend school regularly. He had no insomnia and his appetite was usually adequate, though he showed little interest in food. He gave no evidence of suicidal thoughts or actions and was not using drugs or alcohol, but all who had known him over time were struck by his persistent and increasing unhappiness, lethargy, and seeming inability to enjoy life. Doug has a long history of difficulty falling asleep. He cannot get to sleep unless he is in a room with his brother or a parent. Even then he often is unable to get to sleep until sixty to ninety minutes after he gets into bed. Once in bed he will not leave his bed to go the bathroom unless a parent or his brother accompanies him. Joanne explained, I know it doesn't make sense for me to wash and rewax those floors every night. Most people don't do it even every month. But I have been doing it...

Recovery after a Stroke

After a stroke, many people experience feelings of depression (see page 345). They may feel frustrated or isolated, especially if they have not been able to return to their usual routine or if they are having problems communicating with others. Symptoms of depression include sleeplessness, indifference, and withdrawal. For most of these people, the depression is temporary. It may be helpful for the person to join a support group to share experiences and information with others who are in a similar situation. Talking with a psychiatrist or another mental health professional may help the person cope with and overcome his or her depression. To treat prolonged depression, a doctor may prescribe antidepressant medications such as tricyclic antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, or bupropion.

Clinical Features Of Dementia With Lewy Bodies

The central feature of DLB is a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function, whereas core clinical components comprise fluctuating cognition, recurrent and persistent visual hallucinations, and extrapyramidal signs (EPS). Supportive features may increase diagnostic sensitivity, though exclusion criteria also need to be considered (Table 1). Depression and REM sleep behavior disorder (RBD) have been suggested as additions to the list of supportive features (4). g. REM sleep behavior disorder (4) Falls, Syncope, Sleep Disorders, and Other Neurological Features

Generalized Anxiety Disorder351

Tic worry or dread about the circumstances of daily life. The excessive worries often pertain to many areas of the affected person's life, including work, relationships, finances, personal health, the well-being of one's family, perceived misfortunes, and impending deadlines. Affected people can experience a variety of symptoms, including feelings of fear and dread, restlessness, muscle tension, a rapid heart rate, light-headedness, poor concentration, insomnia, increased perspiration, cold hands and feet, and shortness of breath. Symptoms typically worsen during stressful periods.

Nontricyclic Antidepressants

The other nonstimulant medication recommended by the American Academy of Pediatrics (2001) as a second-line treatment for ADHD is bupro-prion (BUP). Marketed under the brand names Wellbutrin and Zyban, buproprion is classified as an antidepressant, but its chemical structure is quite different from that of most other medications in this class. BUP acts on the noradrenergic system and indirectly on the dopaminergic system. Controlled studies have found BUP to be effective for treating ADHD in children (two trials) and adults (two trials). One open-label study found BUP useful for treating patients with ADHD and comorbid bipolar disorder. Wilens and colleagues (2002) suggested that treatment with BUP for ADHD patients should be initiated at 37.5 mg and increased every three or four days up to a maximum of 300 mg daily in younger children and 450 mg daily in older children or adults. Adverse effects may include excessive activation, irritability, insomnia, and (rarely) seizures.

Symptoms And Signs

The incubation period is highly variable and may range from 10 days to more than 1 year, in most cases 2-10 weeks. The risk of becoming infected depends on the nature and location of the bite. Severe bites involving the head or neck are considered to carry the highest risk, and in such cases clinical disease may develop after a relatively short incubation period. In addition to site and severity of the bite, the virus concentration in the saliva of the animal is important. A few days before clinically manifest disease the patient may experience non-specific symptoms such as malaise, restlessness, insomnia and depression. The most common manifestation of rabies is the so-called 'furious' (rabid) rabies, where the clinical picture is dominated by periods of intense hyperexcitability, hyperactivity and aggression, commonly combined with hyperventilation, hypersalivation and convulsions. Between such attacks the patient is usually anxious and exhausted, but well orientated. Hydrophobia as...

Adverse Event Profile Of Tnp470

408) and anorexia and vomiting (two each of 408). The greatest incidence of severe or grade 3 or 4 AEs involved neurological function (16 of 110 AEs, or 14.6 ). In addition to gait disturbances and dizziness, these neurologic AEs included single complaints of vision abnormalities (diplopia, amblyopia, and nystagmus), emotional lability, coordination difficulties, insomnia, nervousness, and vertigo. The incidence of AEs related to central nervous system and visual function increased in a dose-dependent manner, but this was not the case for AEs affecting other systems. Central nervous system AEs of grade 2 or higher severity (moderate or severe) increased in incidence at dose levels of 40 mg m2 and higher, when TNP-470 was administered as a 1-h infusion qod, or every MWF. The incidence of grade 2 or higher (moderate or severe) AEs did not differ between male and female patients.

Eszopiclone Hypnotic [3336

Eszopiclone is a non-benzodiazepine hypnotic agent indicated for the treatment of insomnia to induce sleep and for sleep maintenance. It has similar pharmacokinetic and pharmacodynamic parameters as the previously marketed non-benzodiazepine hypnotics zolpidem and zaleplon. However, unlike its predecessors, eszopiclone is not restricted to short-term treatment of insomnia. Clinical studies of up to 6 months of use show that patients do not develop tolerance to its effect. Eszopiclone is the (S)-enantiomer of zopiclone, which has been marketed as the racemic mixture in Europe for almost 20 years. These agents belong to the cyclopyrrolone class of drugs that act as agonists at the type A GABA receptor. Eszopiclone has approximately 50-fold higher binding affinity than its antipode (R)-zopiclone for GABA-A receptor (IC50 21 and 1130 nM, respectively). In addition, the two enantiomers exhibit significant differences in their pharmacokinetic parameters and in vivo efficacy. In healthy...

Clinical Use Of Theophylline In Asthma

The use of theophylline in chronic asthma is being redefined. Over the 4-yr period from 1989 to 1993, prescriptions for theophylline written by pediatricians decreased from 27 to 7 of all asthma medicines. According to the most recent Expert Panel Report of the National Heart, Lung and Blood Institution's (NHLBI) National Asthma Education of Prevention Program, theophylline has been relegated to a second-line position for patients who fail to respond to optimal p2-agonist and inhaled steroid treatment. However, abundant data accumulated over the past 20 yr indicate that theophylline is as effective as cromolyn in young children and provides additional control of symptoms even in patients taking inhaled steroids. In several well-designed studies of patients with severe asthma, withdrawal of theophylline resulted in significant deterioration in their clinical condition. In addition, many physicians have noted deterioration of asthma in patients previously well controlled with...

Alcohol and substance abuse

Alcohol withdrawal presents as anorexia, insomnia, weakness, combativeness, tremors, disorientation, auditory and visual hallucinations, and convulsions. Onset is usually 10 to 30 hours after abstinence, and the symptoms may last for 40 to 50 hours. Prolonged abstinence may lead to delirium tremens or autonomic hyperactivity (tachycardia, diaphoresis, fever, anxiety, and confusion). Alcohol withdrawal syndrome may occur while under anesthesia and manifest as uncontrolled tachycardia, diaphoresis, and hyperthermia. The treatment is administration of benzodiazepines or intravenous infusion of ethanol.

Nonstimulant Medications for ADHD

Adequate head-to-head research has not yet tested whether ATX provides the same degree of improvement for inattention symptoms of ADHD as the stimulants usually do. But clinical trials have clearly shown in sizable groups of children, adolescents, and adults that, for many, this medication can significantly alleviate both inattention and hyperactive or impulsive symptoms of ADHD. In addition, ATX has the advantage of lasting longer than stimulants. Some parents report that while on ATX their ADHD children are easier to get along with throughout the day and evening, are able to fall asleep with less difficulty at bedtime, and are able to awaken the next morning with less irritability and oppositional behavior. There is also some evidence that ATX may help to alleviate the anxi

The Impact Of Parkinsonism On Healthrelated Quality Of Life

The only parkinsonian disorder that has been assessed in detail with regard to Hr-Qol is PD. Studies on Hr-QoL of patients with PD have improved our understanding of subjectively experienced difficulties associated with this disease, and we now have a clearer understanding of what aspects of Hr-QoL are most important to patients with PD. A full review of the expanding Hr-QoL literature in PD is beyond the scope of this chapter. However, it has consistently been found that all areas of Hr-QoL are affected by PD, not merely the physical impairment or functioning (23,25,26). The main areas of impairment in PD are in physical functioning, emotional reactions, social isolation, and energy. Other domains of impairment of Hr-QoL in PD, include bodily discomfort pain, self-image, cognitive function, communication, sleep, role function, and sexual function (23,25-27). It has also become clear that in PD, it is not primarily disease severity and presence of the symptoms of PD that determine...

Serotonin receptor modulators

Serotonin related compounds devoted to sleep disorders mainly act via 5-HT2A receptors. Compounds in clinical development reported with this mechanism of action are Eplivanserin, Pimavanserin, Pruvanserin, Volinanserin and APD-125. Eplivanserin (39) is a 5-HT2A antagonist initially developed for a broader spectrum of psychiatric disorders but that has been tested recently for insomnia. Within this latter indication, phase II studies showed benefits in sleep maintenance, but not in induction 9 . Compound 39 is currently in phase III, to assess the efficacy for the treatment of sleep maintenance insomnia, evaluating both sleep and daytime functioning 96 . Pimavanserin tartrate (40, ACP-103) is a 5-HT2A receptor inverse agonist currently in phase II clinical development as an antipsychotic agent and for insomnia, focused on sleep maintenance, evaluating slow-wave-sleep at doses of 5 and 20 mg 97,98 . Pruvanserin hydrochloride (41, EMR-62218 LY-2422347) is a 5-HT2A antagonist in phase II...

The Relationships Between Lipid Profile Levels Depression and Suicide Attempts

Depressive symptoms are common in patients with physical illness, including cardiovascular disease, diabetes mellitus, end-stage renal disease, and women in pregnancy, delivery, or menopause. The depressive symptoms in patients with physical illness include apathy, anorexia, sleep disorder, fatigue, and cognitive deficits 42 .

Prognosis And Clinical Predictors

The neurologic examination is the first step in assessing the prognosis of a comatose patient after CA (17). Coma can be defined as a state of unarousable unresponsiveness characterized by the eyes being closed (as in sleep) and the absence of purposeful movements to stimulation (18). Stupor refers to a state of deep sleep, with arousal only to vigorous stimulation. In contrast, patients in vegetative states do not appear asleep but open their eyes to stimulation (although diurnal sleep-wake cycles may develop). This state of wakefulness, however, does not include evidence of cognition or awareness. Spontaneous movements might be observed on general observation of the patient, and determination should be made as to whether they are purposeful, semipurposeful (e.g., appropriate withdrawal from a noxious stimulus) or reflex movements. Some very unusual complex reflex movements have been reported even in brain-dead patients and should not be confused with purposeful motor activity (19).

Key Points Concerns In Patients Taking Cocaine

Signs and symptoms of intoxication include anorexia, diaphoresis, hypertension, tachycardia, hyperthermia, agitation, and psychosis. Patients can also have myocardial infarctions, seizures, strokes, rhabdomyolysis, and renal failure. The withdrawing patient will experience fatigue, irritability, insomnia, anxiety, and psychotic reactions. An unusual sign seen in chronic methamphetamine users is dental decay, known as meth mouth.

Agomelatine and derivatives

Agomelatine 7 is a potent agonist at melatoninergic receptors. It shows a high affinity for cloned human melatonin receptor MT1 and MT2 sub-types (K 61 , and 268 pM, respectively). The affinity of agomelatine at melatonin receptors is comparable to that of melatonin (K 85 and 263 pM, respectively). Agomelatine also shows affinity (IC50 270 nM) for human cloned serotonin-2C (5-HT2C) receptors, and acts as an antagonist at this receptor subtype 63 . Agomelatine has shown antidepressant activity in animal models of depression, e.g. the rat forced swim test (FST) 63 and the rat chronic mild stress model of depression 64 Researchers have suggested that the antidepressant-like activity of agomelatine depends on some combination of its melatonin agonist and 5-HT2C antagonist properties. This novel dual pharmacological profile has been given the acronym MASSA (Melatonin Agonist and Selective Serotonin Antagonist) 51 . Agomelatine, is significantly more potent at melatonin receptors than at...

Neuropsychiatric Symptoms In Multiple System Atrophy

Several studies have reported sleep disorders in MSA (64,103-107). Wright et al. describe a polysomnographically confirmed RBD associated with Shy-Drager syndrome (108). Motor dyscontrol in REM sleep has been described in 90 of patients with MSA (104). Among 93 patients with RBD, 14 patients had MSA, 25 PD, and only 1 had PSP (109). And similarly, in a recent study of 15 patients with RBD, the neuropathological diagnosis was DLB in 12 and MSA in 3 cases (64). In a comparison of unselected patients with MSA (n 57) with 62 age- and sex-matched PD patients, 70 of patients with MSA complained of sleep disorders compared with 51 of patients with PD, and RBD was present in 48 of the MSA patients (106). Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA (107). In summary, MSA patients frequently suffer from depression and sleep disorders, including RBD, and visual hallucinations, also seem to be quite common. Thus, the neuropsychiatry pattern resembles that of DLB...

New MLT agonist structures

Tricyclic compounds, namely those bearing the scaffold dibenzo a,d cycloheptene, have been described as melatonin receptor ligands with MT2 receptor selectivity. Noticeably, 14 is described as an MT2 selective receptor antagonists, with affinity comparable to that of melatonin, while 15 produced a noticeable reduction of GTPgS binding at MT2 receptor, thus being among the few inverse agonists described to date 44 . Audinot et al. have disclosed the compound S-70254 that selectively binds to the MT2 receptor with a Kd of 7.0 pM compared to an affinity higher than 1.0 nM for MT1, but no structure is available for this compound 45 . Other melatonin receptor modulators described by the same group bear the benzo-thiophene sub-structure, 16, with affinity for the human MT1 MT2 receptors (IC50 80 1 nM) 46 or the imidazopyridine moiety, 17 (IC50 29 8 mM) 47 . A series of melatonin analogues has been used to investigate the nature of the binding site of the melatonin receptor. The agonist...

Ht6 Receptor Family

First cloned in 1993 112 , the human 5-HT7 receptor is the newest member of the 5-HT receptor family. The pharmacology, medicinal chemistry and therapeutic potential of 5-HT7 ligands were extensively reviewed in 2004 113-119 . In addition to migraine, depression and schizophrenia, 5-HT7 antagonists may find use in the treatment of sleep disorders and cognitive deficits. The lack of selective 5-HT7 agonists has made the identification of the biological effects of 5-HT7 receptor

Hormonal Lifting

- A healthy sleep This lasts 7-9 h each day. The daily 6 min nap, as taken by the old German chancellor Adenauer or the old Chinese, acts like an oasis of rest in the middle of the day. gredients through the skin include liposomes, oleo-somes, nanocapsules, microspheres, and telomerase. Vitamins such as retinoic acid and D-panthenol are regarded as skin regenerators. Terproline, melatonin, phytohormones, and various moisturizers are used to rejuvenate and regenerate the skin (hyaluronic acid, the amino acids glycin, allantoin, hypotaurin, etc.). Common herbal ingredients include algae, aloe vera, avocado, borage seed oil, ginkgo, soya beans, jojoba oil, and grapes.

Introduction

Between the seventies and eighties there had been a natural evolution in the field of ambulatory-home EEG monitoring. This trend has continued over the past 15 years. Now, the use of ambulatory EEG monitoring for the diagnosis of patients with seizures, sleep disorders, and difficult-to-diagnose episodic events is common.

Sleepwake

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and sudden loss of muscle tone (cataplexy). Antagonism of H3Rs is anticipated to not only reduce excessive somnolence, but also prevent inappropriate transitions into paradoxical sleep states thought to underlie cataplectic episodes. Interestingly, the H3 antagonists thioperamide (1) and JNJ-5207852 decrease episodes of cataplexy in a genetically narcoleptic Doberman Pinscher model 25 , further supporting a potential role for this class of compound in treating narcolepsy.

Ramelteon

Takeda's melatonin (MT1 MT2) receptor agonist ramelteon (11) was approved and launched in 2005 in the U.S., indicated for the treatment of primary insomnia characterized by difficulty with sleep onset. It is the first prescription medication for insomnia with a novel mechanism of action to reach the US market in 35 years. It is also the first and only prescription sleep medication that has not exhibited potential for abuse and dependence, and as such is not designated as a scheduled substance by the DEA. Moreover, ramelteon was also filed in late March 2007 in E.U. for primary insomnia. In controlled clinical trials in patients with primary insomnia, ramelteon 4-32 mg demonstrated significant reduction in latency to persistent sleep (LPS) compared with placebo. In elderly patients, objective and subjective LPS were also reduced at doses of 4 and 8 mg. Data on total sleep time are more variable,

Ht2 Rfpfptors

5-HT2 receptor antagonists - Selective antagonists for the 5-HT2 receptor are available, e.g. ritanserin (42). However, this compound produces only weak behavioral and biochemical effects in various species. Beceause of this, it has been suggested that the 5-HT2 receptor might be a binding site without an important physiological function, or a redundant receptor (69). In man, the best documented clinical effect of ritanserin appears to be an increase in slow-wave sleep, improving the overall sleep quality (70,71). A mixed D2 5-HT2 blocking effect has been suggested to contribute to the beneficial clinical profile of atypical antipsychotics (72).

Stress Management

Muscles tighten as stress starts, often causing intense headaches, backaches, and gastrointestinal problems. Stress also can cause testosterone levels to decrease and blood vessels in the penis to constrict, often resulting in erection problems. The rush of hormones caused by a stressful situation can bring on an asthma attack in a person with a history of asthma. Stress also draws the blood supply away from the abdominal area and encourages overproduction of acids in the digestive system, often leading to indigestion and other gastrointestinal problems. Other problems related to stress include insomnia and irritability.

Kainate Receptors

Thermoregulation, hallucinations and sexual behavior (Werry et al. 2008). The multiple actions of 5HT are mediated by specific interaction with multiple receptor subtypes. Pharmacologic, physiologic and molecular cloning studies have provided evidence for 15 distinct 5HT receptor subtypes which have been subdivided into seven families (5HT1-5HT7) based on relative ligand-binding affinities, genomic structure, amino acid sequence similarities and coupling to specific signal transduction pathways (Barnes and Sharp 1999 Bockaert et al. 2006 Hoyer et al. 1994, 2002). The 5HT2 family of receptors includes three receptor subtypes 5HT2A, 5HT2B and 5HT2C, which belong to the G-protein-coupled receptor (GPCR) superfamily. The G-protein-5HT2C receptor interactions occur in highly-conserved regions of the second- and third-intracellular loops to potentiate subsequent signal transduction pathways via Gaq 11, Ga12 13 and Ga to modulate effector molecules such as phospholipases C, D and A2, as well...

Hallucinations

Formed visual hallucinations are more complex with vivid scenes like a film, sometimes close to real (members of family), sometimes full of fantasy (ninja turtles, dancing Russians, medieval stories), but soundless. In some cases, the hallucinations may be frightening (house burning, wild animals). Auditory hallucinations are rare and tactile hallucinations often involve animals. As they are more frequent in the evening they may be associated with vivid dreams and sleep disorders (15).

Adjunctive Therapy

Adjunctive therapy is intended to promoted drainage of secretions and improve oxygenation to the obstructed sinus ostia. Multiple agents with different mechanisms of action are often administered. These include decongestants that are alpha-adrenergic agonists that constrict the capacitance vessels and decrease mucosal edema. Topical therapy such as oxymetazoline or neosynephrine may be used in an acute setting, but overuse can cause a rebound effect and rhinitis medicamentosa. Systemic decongestants can be used for longer periods of time, but may cause insomnia and exacerbation of underlying systemic hypertension.

Other Uses

EEG monitoring acquires much more data than routine EEGs. It can be better in detecting interictal abnormalities, particularly in patients who have normal baseline EEGs or who have findings of questionable significance such as various sharp transients. Cardiac arrhythmias may also be found. Sleep disorders may be identified, particularly when eye movement, electromyography (EMG), and respiratory function are monitored in addition to the EEG recording of sleep states. Determination of the pr cipitants for seizures can also be detailed through monitoring, e.g.,in catamenial and reflex-related seizure disorders.

What is abnormal

Axis I disorders disorders of infancy, childhood or adolescence cognitive disorders such as dementia and amnesia substance-related disorders psychotic disorders such as schizophrenia mood disorders anxiety disorders somatoform disorders (that is, disorders about the body) factitious disorders (in which symptoms are feigned or consciously produced) dissociative disorders (temporary alterations to consciousness) sexual disorders eating disorders sleep disorders impulse control disorders (such as compulsive stealing or lying) adjustment disorders.

Management

Other treatable comorbid illnesses must also be considered, most notably infections (e.g., pneumonia and urinary tract infections), psychiatric disorders, and sleep disorders. Although psychotic features rarely occur in the CBS, depression evolves in essentially every patient, likely owing in part to the preserved insight that is also characteristic of the disorder. Sleep disorders such as obstructive sleep apnea, central sleep apnea, restless legs syndrome, periodic limb movement disorder, etc. occur with some frequency in the CBS, and treatment can improve quality of life (100). REM sleep behavior disorder is very rare in the CBS in fact if it is present, one must suspect some contribution of synucleinopathy pathology (101). Despite the difficulties of manipulating the headgear as part of nasal continuous positive airway pressure (CPAP) therapy owing to the limb apraxia, CPAP therapy for obstructive sleep apnea can be tolerated and used effectively in many patients. Patients and...

Mental Disorders

Common mental disorders include mood disorders, anxiety disorders, sleep disorders, and psychotic disorders. They can cause a wide variety of symptoms, such as inappropriate anxiety, disturbances of thought and perception, and mood disturbances. These disorders are legitimate medical problems. They do not go away just by trying to shake off the symptoms, and they do not come about because the affected person has a character flaw or weakness. Mental disorders can be triggered by stressful negative or positive life events, such as the loss of a job, a promotion, the birth of a child, or a divorce. Sometimes, however, they occur with no obvious cause, changing the person's personality and affecting his or her work and relationships.

Ch3so3h

And in combination with data from in vitro inhibition of the CYP isozymes, lisdexamfetamine should possess a low potential for drug-drug interactions. Approximately 96 of the radioactivity was recovered in the urine with only 0.3 found in the feces. Regarding the efficacy of lisdexamfetamine, a doubleblind, randomized, placebo-controlled study was conducted in 290 children aged 6-12 years who met DSM-IV criteria for ADHD. Over the course of 4 weeks, patients were randomized to a fixed dose of lisdexamfetamine (30, 50, or 70 mg) or placebo once daily in the morning. Employing the ADHD rating scale, significant improvements in patient behavior were observed at endpoint for all doses compared to placebo. While the mean effects were similar for all doses, the 70-mg dose was superior to the lower two doses. Furthermore, as assessed by the Connor's Parent rating scale, the effects were maintained throughout the day with culmination at the 6 p.m. evaluation. The most common adverse events,...

Organizations

Fatigue Fatigue is different from drowsiness. Drowsiness is feeling the need to sleep, whereas fatigue is a lack of energy and motivation. Apathy (a feeling of indifference or not caring about what happens) and drowsiness can be symptoms of fatigue. Fatigue can be normal after physical exertion or because of lack of sleep. When persisting fatigue is not relieved by enough sleep, good nutrition, or a low-stress environment, it should be investigated. Because fatigue is a common complaint, associated illness may be overlooked. It is a common symptom in MS and other autoimmune disorders. However, there are many other possible physical and psychological causes of fatigue including anemia, hypothy-roidism, infections, sleep disorders, depression, medications, etc. Chronic fatigue syndrome (CFS) is a condition that starts with flu-like symptoms and lasts for 6 months or more. All other possible causes of fatigue are eliminated before this diagnosis is made.

Huntingtons Disease

This perspective also fits the fact that the movements are worsened by emotional or other stress, which, plausibly, is accompanied by an increase of such extraneous activity, afferent to the basal ganglia (Folstein, 1990 Kremer, 2002). The movements cease during deep sleep (Quarrell and Harper, 1991). This could be a consequence of the fact that, in deep sleep, the intricate coordination of activity of the cortex for purposes of information processing is replaced by large coherent electrographic waves. These would activate striatal cells en masse, and the local inhibition (activity control) of the medium spiny neurons that remain intact would cancel out activity in any cell group, which might release specific movements.

Laboratory

Polysomnographic studies show a diminished total sleep time, an increase in awakenings, and progressive loss of REM sleep. These disturbances can be attributed to degeneration of brainstem structures crucial to generate normal sleep patterns, such as the pontine tegmentum, characteristically involved in PSP.

Antihypertensives

The sedating properties of clonidine have been exploited to help alleviate the chronic difficulties in falling asleep that are common in many children with ADHD. Jefferson Prince and colleagues (1996) reported that of sixty-two children and adolescents treated with clonidine about an hour before bedtime, 85 percent had significantly less difficulty falling asleep. Many of these children (68 percent) were being treated successfully with stimulant medications during the day and were given small doses of clonidine, typically either a half or full 0.1 mg tablet, about an hour before bedtime. Because many patients with ADHD suffer from one or more comorbid psychiatric disorders, one medication is often not sufficient to control their symptoms. For example, as described above, many patients whose ADHD symptoms respond well to treatment with stimulants throughout the day continue to have great difficulty falling asleep at night. A significant percentage of these patients experience much less...

Tinnitus

Tinnitus is the medical term for ringing or other sounds in the ears that occur when there is no external source of these sounds. It is a very common condition, affecting an estimated 35 million people in the United States each year. It is estimated that 1 to 5 percent of these people have tinnitus so severe that it affects their ability to lead a normal life. Symptoms include ringing, hissing, buzzing, or whistling in one or both ears. The symptoms may be constant or come and go, the pitch can vary from high to low, and the sound can pulsate in time with the heartbeat. One type of tinnitus causes clicking or crackling sounds. These annoying sounds can be a major source of distraction and irritation, affecting performance at work and other daily activities. Tinnitus can make it difficult for the person to fall asleep.

Schizophrenia

Fatal familial insomnia (FFI) Gerstmann-Straussler-Scheinker disease (GSS), and fatal familial insomnia (FFI). In these disorders, an abnormal prion protein converts normal prion molecules into abnormal forms by a process that is not yet fully understood. Either the accumulation of prion protein with an abnormal conformation or the loss of normal prion protein causes neurodegeneration. Familial CJD accounts for about 15 of all cases of human spongio-form encephalopathies. The clinical features of CJD are first recognized between the ages of 60 and 65 and include tremors. Patients later become stuporous, and death occurs 6 to 12 months from the inception of the disease. The cerebral cortex is the primary site of neuronal loss in CJD patients. Both GSS and FFI are very rare, and neurodegeneration occurs mainly in the cerebellum and thalamus, respectively.

Hirsutism In Abdomen

The prevalence of sleep disorders, particularly sleep apnea, is high in women with PCOS (31,32). Its principal symptoms are a significant degree of snoring and daytime sleepiness (32). Sleep apnea is caused by repeated collapse of the pharynx airway during sleep, resulting in poor oxygen supply to the person involved. Its consequences include daytime sleepiness, reduced mental performance, and a subsequent effect on quality of life. Its incidence is 2-4 in normal men and women, and it has dangerous consequences, including the development of hypertension, heart attacks, and strokes (33). It usually is associated with obesity, and its prevalence is 3- to10-fold higher in men than in women in fact, excess male hormones may be associated with the development of sleep apnea (34,35).

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