Insomnia Treatment Diet

Outsmart Insomnia

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Measuring Sleep Disorders

Until 2002, there were no specific instruments to clinically assess sleep problems of PD in a comprehensive and holistic fashion. Existing sleep scales for other disorders, such as the Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale, or the Karolinska Sleepiness Scale, are not specific for PD and have problems related to scale clinimetrics in relation to complexity and face validity when these are used in PD (66, 71-73). For instance, the PSQI, although quantifiable, does not specifically address sleep disturbances of PD, such as restlessness of legs, painful posturing of arms or legs, tremors, or fidgeting. The Stanford Sleepiness Scale and the Karolinska Sleepiness Scale appear too short for a comprehensive assessment of sleep problems. The gold standards for measurement of physiological aspects of sleep architecture are PSG and MSLT. However, these are tests of sleep structure, need specialized sleep laboratories, and can be expensive. In the United Kingdom, for...

Sleep Benefit and Sleep Hygiene

Sleep benefit is a common phenomenon of variable duration ranging from 30 minutes to 3 hours in PD and implies improvement in mobility and motor state in the morning and after drug intake at night (98). The mechanism of sleep benefit is unknown, and possible causes include (i) recovery of dopaminergic function and storage during sleep, (ii) a circadian rhythm-related phenomenon, or (iii) a pharmacological response to dopaminergic drugs (7,30). Good sleep hygiene is also useful. Activities such as a hot bath a couple of hours before bedtime, maximizing daytime activity, ensuring bright light exposure, having a hot sweet drink or a light snack at bedtime, use of handrails in bed and or satin sheets to enable easier turning in bed, flexible bed times, a reclining armchair for some, and avoiding stimulants such as tea or coffee at bedtime are part of good sleep hygiene (81). Nocturia remains one of the most common causes of sleep disruption in PD and can be reduced by avoiding diuretics,...

Pharmacological Toxicological Effects 51 Insomnia

Donath and colleagues performed a randomized, double-blind, placebo-controlled, cross-over study assessing the short-term (single dose) and long-term (14-day multiple dosage) effects of valerian extract on sleep structure and sleep quality. There were significant differences between valerian and placebo for parameters describing slow-wave sleep (SWS) and shorter sleep latency, with very low adverse events. Leathwood and colleagues demonstrated valerian's effect on sleep quality (11). A freeze-dried aqueous extract of valerian root (Rhizoma Valeriana officinalis L. ) 400 mg was compared to two Hova (valerian 60 mg and hop flower extract 30 mg per tablet) tablets and placebo (finely ground brown sugar) in this crossover study involving 128 volunteers. Study participants took the study medication 1 hour before retiring, and filled out a questionnaire the following morning. This was repeated on nonconsecutive nights, such that each of the three treatments, identified only by a code...

Circadian rhythm sleep disorder

Circadian rhythm sleep disorder is a persistent or recurring pattern of sleep disruption resulting either from an altered sleep-wake schedule or an inequality between a person's natural sleep-wake cycle and the sleep-related demands placed on him or her. The term circadian rhythm refers to a person's internal sleep and wake-related rhythms that occur throughout a 24-hour period. The sleep disruption leads to insomnia or excessive sleepiness during the day, resulting in impaired functioning. sleep disorder as one of several primary sleep disorders. y Within the category of primary sleep disorders, it is clas- h Circadian rhythm sleep disorder involves an alteration of an individual's circadian system or a mismatch between a person's natural, or endogenous, circadian system and the external, or exogenous, demands placed on it. It can lead to insomnia at certain times of the day or excessive sleepiness throughout the day. The insomnia or excessive sleepiness results in impaired...

Effects of Exogenous GH Administration on Sleep Quality

Early studies in rats and in cats indicated that injections of exogenous GH may stimulate REM sleep (94,95). In humans, the stimulation of REM sleep was confirmed in a study involving an intramuscular GH injection administered 15 min before bedtime (96). In addition, this treatment resulted in a decrease in SW sleep. A more recent study reported no effects on sleep quality when GH levels were elevated either by intravenous infusion or by intramuscular injection given approx 3 h before sleep onset (97). As indicated above, in GH-deficient subjects, prolonged treatment with daily injections of exogenous GH resulted in a marked increase in REM sleep (92).

Effects of GHRH on Sleep Quality

A number of studies have demonstrated effects of GHRH on sleep quality and it has been suggested that GH secretion and sleep may share common regulatory mechanisms (98). In rodents, intracerebral as well as systemic injections of GHRH stimulate non-REM sleep, even in hypophysectomized animals (99-102). Systemic injections of GHRH also stimulate REM sleep in intact, but not in hypophysectomized rodents (101,102). Conversely, inhibition of endogenous GHRH using GHRH antagonists or antibodies to GHRH decreases both non-REM sleep and GH secretion (98,103) .Inhumans, discrepant data have been reported. No effects of GHRH on visually scored sleep stages were found when the peptide was injected during daytime or before sleep onset (104,105), or when it was given as an infusion (97,106). However, delta power during the first 100 min of sleep was significantly enhanced following bedtime injection of GHRH (105). When the intravenous injections were performed during sleep, stimulatory effects on...

Other drugs for anxiety and insomnia

For insomnia, long-established remedies include chloral hydrate and promethazine newer drugs include zopiclone. Hypnotics are recommended for occasional use only dealing with the cause of the insomnia is a better alternative to drugs. Causes include noise, discomfort, a restless partner, worry, shift work, travel, excess alcohol or caffeine intake, or unrealistic expectations about the amount of sleep required.

Sleep Quality in the Elderly

Sleep is of great importance for health and the quality of life. There is a strong association between sleep disorders on the one hand, and illness and early death on the other. The mortality is higher among elderly persons with sleep disorders than in those who sleep well, and the excess mortality is related to the predominant causes of death, such as heart disease, stroke, cancer, and suicide. Poor sleep also shows a negative interaction with many somatic and psychiatric diseases and symptoms, as well as causing a deterioration in the quality of life. These diseases and symptoms are more important in explaining sleep deterioration than the age and sex of the patients, although there is a tendency toward an increase in sleep problems with increasing age. There are some evident differences in sleep between men and women. Women report more difficulties in initiating and maintaining sleep than men, whereas men display more sleep disturbances at EEG assessments. Men are also more...

Actions of Melatonin on Anterior Pituitary

Melatonin inhibits the secretion of LH and FSH induced by GnRH. In particular, this has been demonstrated with anterior pituitary cells obtained from 1-to 20-day-old rats. The inhibition by melatonin was effective in the range 0.1-1.0 nM when the cells were obtained from animals that were 5, 10, or 15 days of age. Suppression of anterior pituitary hormone release ranged to 50 of the full response to GnRH, as shown in Figure 18-11. Melatonin interferes either with the GnRH stimulation of anterior pituitary hormone release or with the secretion process, probably through an indirect mechanism. It has been shown in cultured pituitary glands from prepubertal rats that melatonin inhibits GnRH-induced LH secretion. Considering that GnRH has a signal transduction system involving phosphatidylinositol cycle activation, whereas melatonin signals the inhibition of adenylate kinase with a FIGURE 18-10 Postulated melatonin receptor-binding site model. This model shows two possible hydrogen-bonded...


In clinical practice, lemon balm is often prescribed in combination with other herbs such as valerian in the treatment of insomnia. As a reflection of this, a randomised, double-blind multicentre study investigated the effects of a commercial valerian and lemon balm herbal combination (Songha Night) in 98 healthy subjects (Cerny & Schmid 1999). Treatment was administered over a 30-day period and consisted of 3 tablets taken half an hour before bedtime, providing a total dose of 1-6 g valerian and 1-2 g lemon balm. Herbal treatment was found to significantly improve sleep quality and was well tolerated. Another randomised, double-blind crossover study found that the same combination of valerian and lemon balm taken over 9 nights was as effective as triazolam in the treatment of insomnia (Dressing et al 1992). The dose used was equivalent to 1.4 g dried valerian and 0.9 g dried lemon balm. As with all herbal combination studies, it is difficult to determine the contribution each...

Sleep disorders

Sleep disorders are chronic disturbances in the quan- er tity or quality of sleep that interfere with a person's ability to function normally. An estimated 15 of Americans have chronic sleep problems, while about 10 have occasional trouble sleeping. Sleep disorders are listed among the clinical syndromes in Axis I of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, also known as the DSM. They may be either primary (unrelated to any other disorder medical or psychological) or secondary (the result of physical illness, psychological disorders, or drug or alcohol use). In the revised fourth edition of the DSM (DSM-IV-TR), the primary sleep disorders are categorized as either dyssomnias or parasomnias. Dyssomnias pertain to the amount, quality, or timing of sleep, whereas parasomnias pertain to abnormal behavioral or physiological events that occur while sleeping. Dyssomnias include Primary insomnia difficulty getting to sleep or staying...

Melatonin Receptor

Specific melatonin-binding sites have been defined by using 2-125I iodomelatonin as a radioactive ligand. High-affinity sites have been found in suprachiasmic nuclei and pars tuberalis. The levels of the melatonin receptor(s) in these structures are inversely related to the plasma concentration of melatonin. Consequently, the level of melatonin receptors is increased during the day. The light-dark cycle appears to be the regulatory factor. The density of melatonin receptors decreases during the night, even in pinealectomized animals. One hour of light can reverse the nightime decrease in the suprachiasmic nuclei. There is evidence, however, that the mechanisms that regulate these changes in receptor activity in the two structures are different. In the pars distalis, for example, inhibition of Ca2+ influx and membrane potential are important mediators of melatonin effects. Evidence has been presented for the presence of melatonin receptors in rat liver nuclei, leading to the conclusion...

Plant Part Used Chemical Components

It has been shown that dietary melatonin directly contributes to the circulating level of the hormone. The clinical effects of plant-derived melatonin remains to be investigated (Hardeland & Poeggeler 2003). Baicalin itself is poorly absorbed from the gut, but is hydrolysed to its aglycone, baicalein, by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body (Akao et al 2000).

Mark Tuszynski MD PhD

Handbook of Sleep Disorders, edited by Michael J. Thorpy Management of Acute Stroke, edited by Ashfaq Shuaib and Larry B. Goldstein Sleep Disorders and Neurological Disease, edited by Antonio Culebras Handbook of Ataxia Disorders, edited by Thomas Klockgether The Autonomic Nervous System in Health and Disease, David S. Goldstein Axonal Regeneration in the Central Nervous System, edited by Nicholas A. Ingoglia and Marion Murray

Schemata And Cognitive Processes

Guarnaccia, 1989 Kleinman et al., 1986 Krause & Carr 1978). Symptoms of nervios include, headaches, trembling, heart palpitations, stomach and appetite disturbances, trouble with concentration, sleep problems, and worrying (Guarnaccia & Farias, 1988). Sufferers are more frequently women than men, and they are disportionately from rural and lower class backgrounds.

Posttraumatic Stress Disorder

Although there are many forms of psychological injury that can be the focus of a compensation claim (including chronic pain, cognitive impairment, postconcussive syndrome, depression), this review will focus onposttraumatic stress disorder (PTSD). This condition is diagnosed when the individual has (a) suffered a traumatic experience, and subsequently suffers (b) re-experiencing (e.g. flashbacks, nightmares), (c) avoidance (e.g. effortful avoidance of trauma-related thoughts, emotional numbing), and (d) hyperarousal (e.g. insomnia, irritability) symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV American Psychiatric Association, 1994), PTSD has the distinctive feature of including a precipitating stressor as part of the disorder's definition. This establishes a straightforward connection between a triggering traumatic event and a variety of observed symptoms (Freckelton, 1997). Such a relationship enables PTSD to be susceptible to...

Epidemiology And Symptoms

Sleep dysfunction in PD is multifactorial, and as many as 98 of patients with PD may suffer at some time from nocturnal symptoms that can disturb their sleep (2). Overall prevalence figures range from 25 to 98 (2-4). A community-based study reported 60 of PD patients with sleep problems, compared with 33 of age- and sex-matched healthy controls (4). The NMSQuest study in 123 PD patients across all age groups and 96 age-matched controls, using a validated nonmotor symptom questionnaire in an international multicenter setting, identified high rates for a range of sleep-related disorders (14). Although some complaints such as nocturia (67 ) were common in controls, other complaints such as insomnia (41 ), intense vivid dreams (31 ), acting out during dreams (33 ), restless legs (37 ), and daytime sleepiness (28 ) were more prevalent in PD and may reflect more fundamental dysfunction of sleep-related mechanisms. In another observational study, Hely et al. (15) evaluated PD patients for a...

Causes and symptoms

A second cause of anti-anxiety drug abuse is the use of these drugs, especially when combined with other drugs, such as cocaine. It is not uncommon for an addict to pair the use of a stimulant, such as cocaine or metham-phetamine, with a CNS depressant. This allows the user to feel alert for an extended period of time, and then be able to come down from the high, and even fall asleep.

Rapid Eye Movement Behavior Disorder and Restless Legs Syndrome

The treatment of choice for RBD is clonazepam, a benzodiazepine, although the mechanism is unknown and there are no controlled trials (13). Other drugs thought to be helpful for RBD include pramipexole, levodopa, carbamazepine, donepezil, and melatonin (64,89-91). Caution needs to be exercised with the use of clonazepam, as in some cases, RBD may be confused with sleep apnea, which can be worsened by clonazepam. Nighttime dosing with drugs such as selegiline may aggravate RBD. Others have reported a paradoxical worsening of RBD with deep brain stimulation (DBS) of the subthalamic nucleus (STN) (92).

Psychologic problems

Depressive disorders contribute to more than half of all cases of CPP. Frequently, the pain becomes part of a cycle of pain, disability, and mood disturbance. The diagnostic criteria for depression include depressed mood, diminished interest in daily activities, weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness, loss of concentration, and recurrent thoughts of death.

Mental features of depression

Sleep disturbances include difficulty in getting to sleep, so-called 'initial insomnia' disturbed sleep with frequent wakening and early-morning wakening. This last is a classic symptom of a depressive illness, and is often coupled with diurnal mood variation that is, the patient wakes up early in the morning in a very depressed mood, which is then at its lowest point of the 24 hours. During the day, the mood gradually brightens as the patient gets going. Traditional teaching has this pattern as indicative of an endogenous depressive illness, that is, one coming from within the patient, in contrast to an exogenous or reactive depression due to external causes, where the sleep disturbances were said to be more in the nature of initial insomnia. Perhaps unfortunately, research has not borne out these intuitively attractive patterns, and the endogenous reactive classification of depressive illnesses is no longer regarded as useful for therapeutic or prognostic purposes, although,...

Clinical classification of depression

A 22-year-old man was brought to the GP by his girlfriend, who complained that over the previous few weeks he had become increasingly 'moody and withdrawn', and had been drinking too much. The GP, who had known him for years, was struck by his gaunt and miserable appearance, but was nevertheless surprised when, after his partner left the consulting room, the patient broke down in tears. There was a clear history of depressed mood, loss of interest in things which he usually found pleasurable, poor sleep with terminal insomnia, poor appetite with weight loss, and inability to concentrate, leading to problems at work.

Patients Description Of Pain And Meaning

The location, temporal nature, description by the patient (e.g., whether it is sharp, dull, aching, stabbing, pulsating, buzzing, numb, burning, tingling, cramping), and activities that might be the cause of the pain can provide valuable clues that might eventually lead to the correct therapeutic regimen. Also, listen for key descriptions associated with depression, such as insomnia, loss of appetite, loss of hope, irritability, and short-tempered actions with loved ones.

Epidemiology Prion Diseases

Years) and readily identifiable clinically. The incidence of CJD has not changed significantly during this period. In addition to CJD, other human prion diseases include kuru, fatal familial insomnia (FFI ), and Gerstmann-Straussler-Scheinker disease (GSS). Kuru was transmitted by ritualistic cannibalism among the Fore people of New Guinea, with no new cases reported since this practice was stopped. FFI and GSS, rare prion diseases caused by mutations in the prion protein gene, are discussed later in this chapter.

Genetics Prion Diseases

The same point mutation at codon 178, which substitutes an asparagine for an aspartic acid, can result in two distinct phenotypes. The first pheno-type associated with the codon 178 mutation was a form of familial CJD. The clinical course and pathology was similar to sporadic CJD, except that it had a younger mean age of onset (46 versus 62 years), longer average duration (23 versus 6 months), and absence of periodic electroencephalograph activity (Brown et al., 1992). Soon after this association was found, it was discovered that the same codon 178 mutation could cause FFI (Medori et al., 1992). FFI is characterized clinically by untreatable insomnia, dysautonomia, and motor signs and pathologically by selective degeneration of the anterior ventral and mediodordal thalamic nuclei. This paradox of the same point mutation causing two very distinct phenotypes was solved when it was determined that the genotype at the codon 129 polymorphism determines whether patients with codon 178...

Electroconvulsive therapy ECT see Chapter

As previously indicated, ECT has a place in emergency treatment, and when other treatments have failed. It is currently infrequently used, but tends to have good results in the more severe cases in which it is utilized. ECT is effective in about 80 per cent of patients with severe depression, notably in psychotic cases with delusions or hallucinations. Mild depression seldom responds well to ECT. Prescribing an antidepressant alongside ECT is usually recommended. Benzodi-azepines, used for insomnia or anxiety, should be stopped before ECT is started, as their anticonvulsant properties will interfere with the effectiveness of ECT in producing a convulsion.

Selective Serotonin Reuptake Inhibitors

The SSRIs are relatively well tolerated, although acute, treatment-emergent side effects such as agitation, diarrhea loose stools, insomnia, nausea, and sedation may occur. Occasionally, SSRIs may worsen tremor, and chronic use is associated with an increased risk of developing endocrinologic and metabolic adverse effects, such as hyponatremia, sexual dysfunction, and weight gain (Table 1) (50-52). The concomitant use of amantadine has been reported to reduce the risk of SSRI-induced sexual dysfunction (53). Reversible SSRI-induced worsening of parkinsonism has also been reported, but data are conflicting regarding the magnitude of this risk (54-56). Pharmacodynamic studies have not detected any significant reduction of motor function in patients with PD treated with SSRIs (57-58). Patients on a concomitant monoamine oxidase-B (MAO-B) inhibitor (e.g., rasagiline, selegiline) may be at increased risk of developing 5-HT syndrome however, the overall risk appears to be minimal. In one...

Diagnosis Prion Diseases

A familial prion disease is suggested by a family history consistent with autosomal dominant inheritance of an atypical dementia and or ataxia. However, some patients with familial prion diseases do not have an informative family history (e.g., adopted patient without knowledge of biologic family). The non-CJD presentations of familial prion disease (e.g., GSS and FFI ) are difficult to diagnose without prior tissue confirmation of other family members. When patients present with slowly progressive ataxia without dementia (e.g., GSS), the variety of diseases that cause progressive cerebellar dysfunction need to be considered in the differential diagnosis, including the spinocerebellar atrophies. FFI or thalamic forms of CJD are suspected if intractable insomnia and dysautonomia develop, especially if there is a family history of similar cases. If a familial form of CJD is suspected, prion protein gene analysis is available in research laboratories to look for pathogenic mutations.

Detection and Assessment

The DSM-IV diagnostic criteria for major depression includes the persistent presence of five of the following nine symptoms anhedonia, depressed mood, diminished ability to think or concentrate, fatigue or loss of energy, feelings of worth-lessness or inappropriate guilt, insomnia or hypersomnia, psychomotor agitation or retardation, recurrent thoughts of death, and significant weight gain or loss (36). However, because several of these symptoms overlap with features of PD, the assessment of depression in patients with PD is not always straightforward. This is highlighted by a study demonstrating that anergy, early morning awakening, and psychomotor retardation are common and similarly frequent in both depressed and nondepressed patients with PD (105).

Functional Expression Of G Proteincoupled Receptors In Yeast

The heterologous yeast expression system for GPCRs can also be used to examine structure-function relationships that are difficult to study genetically using other systems, including elucidation of ligand binding sites and GPCR interactions with heterotrimeric G proteins, agonist activation of GPCR activity, and the response to surrogate agonists. Mutations in GPCRs or their signaling pathways can be identified using genetic selections based on the growth phenotype. Constitutively active and dominant-negative mutants of the yeast a factor receptor were identified using genetic approaches that could be employed to identify mutants of heterologous GPCRs 91,92 . In addition, the yeast expression system was used to identify amino acid residues involved in melatonin receptor activation of hetero-trimeric G proteins 93 . Similar genetic approaches should be useful for the dissection of the interactions within the heterotrimeric G protein complex, with RGS proteins, and with downstream...

Pathophysiology of Psychosis and Risk Factors

The presence of dementia, advancing age, impaired vision, depression, sleep disorders, and longer disease duration have all been associated with the development of drug-induced psychosis (15,45-48). Although psychosis has been reported to occur with all of the antiparkinsonian medications (22-25), the dopamine agonists are more likely to cause psychosis than levodopa (49,50). The duration or dose of antiparkinsonian drug therapy, however, has not been found to be associated with an increased risk for psychosis (45,51,52).

Caffeinerelated disorders

In the clinician's handbook for diagnosing mental disorders (the Diagnostic and Statistical Manual of Mental Disorders, known as the DSM-IV-TR), caffeine-related disorders are classified under the rubric of substance-related disorders. DSM-IV-TR specifies four caffeine-related disorders caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified. A fifth, caffeine withdrawal, is listed under the heading of Criteria Sets and Axes Provided for Further Study.

Regulatory Status

The German E Commission has approved St. John's wort for internal consumption for psychogenic disturbances, depressive states, sleep disorders, and anxiety and nervous excitement, particularly that associated with menopause. Oily Hypericum preparations are approved for stomach and gastrointestinal complaints, including diarrhea. Oily Hypericum preparations are also approved by the Commission E for external use for the treatment of incised and contused wounds, muscle aches, and first degree burns (96).

Sexual Differentiation Of Vocal Control Areas In Adulthood

In adulthood, next to androgen and estrogen receptors, vocal neurons express receptors for non-gonadal hormones, in particular the pineal hormone melatonin (Gahr and Kosar, 1996 Jansen et al., 2005), and are sensitive for modulatory action of monoaminergic systems (Appeltants et al., 2001, 2002 Sakaguchi et al., 2000). These neurochemical phenotypes suggest that vocal phenotypes are under the control of multiple environmental signals that directly act on vocal neurons, bypassing in part the gonadal system. Such mechanisms might explain the impact of the sociosexual and physical environment on the differentiation of vocal areas and on song development and performance that appears independent of gonadal hormones (Bentley et al., 1999 Deviche and Gulledge, 2000 Gulledge and Deviche, 1998 Tramontin et al., 1999). The most direct evidence suggesting non-gonadal plasticity of vocalization comes from works on adult male zebra finches melatonin affects their song pattern and the...

Aging Markers Based On Behavior And Circadian Rhythms

It has been reported that zebrafish is a diurnal vertebrate with a clear circadian pattern of daytime activity and nighttime rest (Cahill, 1996 Cahill, 2002 Dekens et al., 2003 Delaunay et al., 2000 Hurd et al., 1998 Kazimi and Cahill, 1999). Zhdanova has been studying the sleep-like state in zebrafish, using a high-throughput image-analysis system (Zhdanova et al., 2001). Previous studies have shown that the sleep-like state in zebrafish has fundamental similarities with sleep in mammals, including characteristic postures, elevated arousal threshold to sensory stimulation and a compensatory rest rebound following rest deprivation (Zhdanova et al., 2001). ''Sleep'' in zebrafish can be induced by conventional hypnotics, diazepam and sodium pentobarbital, and the circadian hormone melatonin (Zhdanova et al., 2001). While the age-related decline in human sleep is a well-known phenomenon, it is not yet established whether this is true in lower vertebrates. In order to determine whether...

Introduction To Mood Disorders And Limitations Of Current Treatments

Bipolar disorder and unipolar depression are classified as mood disorders. They are common, severe, and chronic illnesses. Depression is typified by a depressed mood, anhedonia (inability to experience pleasure), feelings of worthlessness or excessive guilt, impaired sleep (either insomnia or hyper-somnia), cognitive and concentration deficits, psychomotor changes, recurrent thoughts of death or suicide, and a variety of neurovegetative symptoms. In bipolar disorder, patients typically alternate (albeit not in a one-to-one manner) between episodes of depression (mostly indistinguishable from unipolar depression) and episodes of mania, which is characterized by a heightened mood, hyperaroused state, racing thoughts, increased speed and volume of speech, quicker thought, brisker physical and mental activity levels, inflated self-esteem, grandiosity, increased energy (with a corresponding decreased need for sleep), irritability, impaired judgment, heightened sexuality, and sometimes...

Lithium Salts As Medication

As mentioned, lithium represents a common treatment for bipolar disorder. Lithium salts were first used therapeutically in the nineteenth century as remedies for sleeplessness and gout. Since the report of their efficacy in the treatment of bipolar disorder in the late 1940s by John Cade, lithium has been widely used in the treatment of acute manic symptoms and mood episode prophylaxis 21 . As mentioned, a number of double-blind studies have confirmed lithium's efficacy both in the acute treatment of mania, and for mania prophylaxis 14 . Further, multiple studies have suggested that lithium may be useful for both the acute and prophylactic treatment of depression (see 22 and 23 for meta-analysis and review). Unfortunately, many of the studies addressing monotherapy antidepressant effects had with some methodological shortcomings in particular, low sample sizes and the use of crossover study designs. In clinical experience, lithium's antidepressant effects as monotherapy may be modest,...

Adverse Reactions

Ginseng abuse syndrome (hypertension, nervousness, insomnia, morning diarrhoea, inability to concentrate and skin reactions) has been reported and there has been a report of a 28-year-old woman who had a severe headache after ingesting a large quantity of ethanol-extracted ginseng. Cerebral angiograms showed 'beading' appearance in the anterior and posterior cerebral and superior cerebellar arteries, consistent with cerebral arteritis (Ryu & Chien 1995). High doses (1 5 g day) have been associated with confusion, depression and depersonalisation in four patients (Coon & Ernst 2002).

Stress urinary incontinence

SUI due to sphincter insufficiency is treated with alpha-adrenergic agonists. Phenylpropanolamine or pseudoephedrine is the first line of pharmacologic therapy for women with SUI. Side effects include anxiety, insomnia, agitation, respiratory difficulty, headache, sweating, hypertension, and cardiac arrhythmia. Use caution with arrhythmias, angina, hypertension, or hyperthyroidism. c. Imipramine may be used in patients who do not respond to the above treatment. It has alpha-adrenergic agonist and antic holinergic activities and is reported to benefit women with SUI. Side effects include nausea, postural hypotension, insomnia, weakness, and fatigue.

Phenobarbital Luminal Solfoton

Indications management of generalized tonic-clonic and partial seizures neonatal seizures febrile seizures sedation sleep disorders anxiety. Dose (adult) Infant and children < 12 yrs 10-20 mg kg IV in a single or divided dose, may give additional 5 mg kg dose every 15-30 minutes until seizure is controlled or a total dose of 40 mg kg is reached maintenance infants 5-8 mg kg day IV PO in 1-2 divided doses, children 1-5 yrs 6-8 mg kg day in 1-2 divided doses, children 5-12 yrs 4-6 mg kg day in 1-2 divided doses. Neonates 15-20 mg kg IV in single or divided dose maintenance 2-4 mg kg day in 1-2 divided doses, increase by 5 mg kg day if needed. Clearance hepatic metabolism, 25-50 renal elimination unchanged. Therapeutic level 15-40 mg L. Contraindications preexisting CNS depression, severe uncontrolled pain, porphyria, severe respiratory disease with dyspnea or obstruction. Adverse effects hypotension, drowsiness, cognitive impairment, ataxia, hepatitis, skin rash, respiratory...

Use of Standardized Methods

Given that norms are typically nonexistent and that such culturally appropriate instruments are also lacking, clinicians using standardized measures should approach results with caution. As a general rule, clinicians should interpret and report data consistent across measures in an assessment battery. For example, it is probably reasonable to conclude an American Indian male is depressed if he indicates depressed affect and other depressive symptoms such as insomnia during a clinical interview and testing further reveals an elevated D scale on the MMPI, a positive Depression Index on the Rorschach, and a very slow processing speed within the Performance subtests of the Weschler Adult Intelligence Scale (WAIS). As described below, however, clinicians should routinely utilize other sources of information beyond standardized measures and incorporate this data into any diagnostic formulation.

Tryptophan 5hydroxylase

This reaction is a key step in the formation of the neurotransmitter serotonin, as well as the hormone melatonin, which responds to light and dark periods and is associated with the biological clock in vertebrates. Rat brain stem enzyme, which is stimulated by Fe2 + , is composed of two isozymes, one of which has a molecular weight of 300 000. Despite a monomeric molecular weight of 59 000 it is also claimed to be a tetramer. l-Phenylalanine is a substrate, but not l-tyrosine C113 . Influences in vivo that reduce brain tryptophan concentration cause the enzyme activity to increase, apparently by an increase in Vmax A1920 , an effect that should sustain brain serotonin levels in face of alterations in tryptophan availability. Liver enzyme (that also acts on phenylalanine) is stimulated by 5-fluorotryptophan and 7-azatryptophan by up to 20-fold, and at higher cofactor concentrations by phenylalanine and thienylalanine A791 . Pineal enzyme shows a diurnal rhythm with raised activities at...


The EEG is an important aid in the diagnosis and management of epilepsy and other seizure disorders, as well as in the diagnosis of brain damage related to trauma and diseases such as strokes, tumors, encephalitis, and drug and alcohol intoxication. The EEG is also useful in monitoring brain wave activity and in the determination of brain death. Research is active in determining the role of EEG in the diagnosis and management of mental retardation, sleep disorders, degenerative diseases such as Alzheimer's disease and Parkinson's disease, and in certain mental disorders such as autism and schizophrenia. Delta waves These are irregular, slow waves of 2-3 hertz and are normally found in deep sleep and in infants and young children. They indicate an abnormality in an awake adult.

WAcetyltransferase Martin and Downer 1989

N-Acetyltransferase uses acetyl-CoA to acetylate the amino moiety of arylal-kylamines. In mammalian pineal gland, this enzyme catalyzes the production of N-acetyl-5-hydroxytryptamine, which is the precursor of melatonin. It is also involved in the inactivation of monoaminergic neurotransmitters in insects.

Diagnostic Characteristics

And sleep maintenance insomnia, and the consumption of high carbohydrate snacks during many of the awakenings. It was described recently in detail by Birketvedt et al. (7). Diagnostic criteria for this syndrome are evolving, and it is not included as a diagnostic category in the DSM-IV. Proposed clinical criteria are shown in Table 1.

Night Eating Syndrome

A characteristic circadian neuroendocrine pattern has been observed in a study of the night eating syndrome (7). The presence of elevated 24-hr levels of cortisol provides a biological marker of the stress under which patients are laboring. Blunting of the expected nighttime rise in melatonin and leptin was also found, in intriguing association with the impaired sleep and nighttime snacking of the night eating syndrome.

Allergic rhinosinusitis

To decrease congestion, two strategies are available. The one often employed first by patients is the use of vasoconstrictor agents. These may be used topically, with the problem of rhinitis medicamentosa, rebound vasodilatation that is often worse than the presenting problem. Oral use of decongestants may be effective in ameliorating congestion in some patients but their use may be associated with hypertension and sleep disorders.

Vague General Complaints

More important than determining the underlying, perhaps unconscious, reasons for seeking help, is the immediate task of discerning what is distressing the patient and converting that expression in the patient's own words, language, and concepts to the clinician's terminology and frame of reference. Many individuals from ethnic minority groups will express their distress in nonspecific terms I feel bad, I feel upset, I am nervous (nervios), and so on. It is thus important to attempt to have the patient elaborate on what they are experiencing, by asking them to say more about their distress without suggesting any specific symptom. This requires patience because among some cultural groups emotional distress is often described in terms of physical symptoms or by referring to a specific disturbed organ or body part. Even with careful attempts to elicit greater subjective elaboration, an individual may not provide the necessary information for the clinician to conclude that a particular...

Generalized anxiety disorder

DSM-TV-TR specifies interference with work, family life, social activities, or other areas of functioning as a criterion for generalized anxiety disorder TCD-10 does not mention interference with tasks or other activities as a criterion for the disorder. Both diagnostic manuals mention such physical symptoms as insomnia, sore muscles, headaches, digestive upsets, etc. as common accompaniments of GAD, but only DSM-TV-TR specifies that an adult patient must experience three symptoms out of a list of six (restlessness, being easily fatigued, having difficulty concentrating, being irritable, high levels of muscle tension, and sleep disturbances) in order to be diagnosed with the disorder. symptoms related to high levels of physiological arousal muscle tension, irritability, fatigue, restlessness, insomnia

Venous Leg Ulceration

Chronic venous leg ulceration (VLU) is a common recurrent problem in the elderly population and may result in immobility, with 45 of patients being housebound (Baker & Stacey 1994). As a result, individuals with VLU frequently experience depression, anxiety, social isolation, sleeplessness and reduced working capacity (Leach 2004). CVI, which is characterised by an increase in capillary permeability, inflammatory reactions, decreased lymphatic reabsorption, oedema and malnutrition of tissues, is a precursor to VLU. As HCSE increases venous tone while reducing venous fragility and capillary permeability and possesses anti-oedematous and antiinflammatory properties, it has been speculated that by improving microcirculation, ulceration may be delayed or prevented (Blaschek 2004).

Pharmacological management

Pergolide can be used in treatment, especially with the levodopa 'on-off phenomenon (fluctuations throughout the day). It appears to be most effective when used in combination. The major side effects of pergolide are similar to levodopa. Dyskinesia and nausea are less problematic but severe psychiatric disturbances are more common with bromocriptine. It should therefore be used with caution in patients with a history of confusion or dementia. Selegiline promises to be an effective first-line drug. If there is associated pain, depression or insomnia, the tricyclic agents, e.g. amitriptyline, can be effective.

Screening Overweight

The evidence that childhood overweight increases the risk ofcomorbidity in both childhood and in adulthood emphasizes the need to identify overweight children with other risk factors as early as possible. The Expert Committee (37) also recommends that all children and adolescents with a BMI > 85th centile be screened for complications, evaluated, and possibly treated, depending on the findings. The complications that should be sought include hypertension, dyslipidemias, orthopedic disorders, sleep disorders, gallbladder disease, and insulin resistance. In addition, a recent large change in a child's BMI should also be evaluated. The Expert Committee emphasized that clinicians should also seek signs of exogenous obesity such as genetic syndromes, endocrinologic disease, and psychologic disorders. In addition to screening, the committee advocated that an in-depth medical assessment be done for all children and adolescents with a BMI > 95th centile.

Chronic Renal Failure

History of the Present Illness Oliguria, current and baseline creatinine and BUN. Diabetes, hypertension history of pyelonephritis, sepsis, heart failure, liver disease peripheral edema, dark colored urine, rashes or purpura. Hypovolemia secondary to diarrhea, hemorrhage, over-diuresis glomerulonephritis, interstitial nephritis. Excessive bleeding, flank pain, anorexia, insomnia, fatigue, malaise, weight loss, paresthesias, anemia.

Sleepwalking disorder

Sleepwalking disorder is one of several sleep disorders listed in the Diagnostic and Statistical Manual of Mental Disorders, often called DSM-IV-TR, produced by the American Psychiatric Association and used by most mental health professionals in North America and Europe to diagnose mental disorders. There appears to be a genetic component for individuals who sleepwalk. The condition is 10 times more likely to occur in close relatives of known sleepwalkers than in the general public. These families also tend to be deep sleepers. No recollection of the sleepwalking incident Upon waking, the person typically has no memory of the sleepwalking events. If the individual does awaken from the sleepwalking episode, they may have a vague memory of the incident. Often, sleepwalkers will return to bed, or fall asleep in another place with no recall as to how they got there. I especially if episodes are infrequent and pose no hazard o to the sleepwalker or others. If sleepwalking is recurrent, or...

The Effects of Glutamate Receptor Subtype Ligands on Morphine Withdrawal Symptoms

Cessation of the repeated administration of opiates results in a characteristic morbidity in humans, including anxiety, nausea, insomnia, hot and cold flashes, muscle aches, perspiration, and diarrhea (1). Great strides have been made in understanding the neurophysiology underlying these opiate-withdrawal symptoms. Several neurotransmitter systems have been shown to play an important role in opiate withdrawal, including the dopaminergic (2-4) and cholinergic (5-7) systems. This chapter will discuss evidence for a role of the glutamate system in morphine withdrawal. Specifically, the idea that morphine withdrawal is a state of glutamate hyperactivity in defined brain regions will be discussed. One of those brain regions is the locus coeruleus.

Pharmacological Stimulation of Slow Wave Sleep

GHB is a metabolite of gamma-aminobutyric acid (GABA) that is normally present in the mammalian brain and is thought to be acting as a neurotransmitter (56-58). GHB readily crosses the blood-brain barrier but has a short duration of action, which limits its use for the treatment of insomnia. A recent study showed that bedtime administration of GHB, even at a very low dose, results in a twofold increase in the amount of GH secreted during sleep (59). This effect of GHB on nocturnal GH secretion resulted from an increase in the amplitude and the duration of the normal secretory pulse associated with sleep

Relationship Between Gh Secretion And Sleep In Pathological States

A few studies have examined nocturnal GH secretion in patients with obstructive apnea before and after treatment (82-84). As expected, nocturnal GH release is decreased in untreated apneic subjects. Because adult patients with this pathology are frequently obese, the low overnight GH levels could reflect the hyposomatotropism of obesity, rather than result from the shallow and fragmented nature of their sleep. However, two studies that have examined the nocturnal GH profile before and after treatment with continuous positive airway pressure (CPAP) have demonstrated that treatment of the sleep disorder resulted in a clear increase in the amount of GH secreted during the first few hours of sleep (83,84). An example is illustrated in Fig. 7. In children, surgical correction of obstructive sleep apnea may restore GH secretion and normal growth rate (82). A number of studies have examined sleep quality and GH secretion in depression and have generally observed a decrease in nocturnal GH...

Modulatory Effects Of Components Of The Somatotropic Axis On Sleep

Although the association between sleep and GH release has been well documented, there is also good evidence to indicate that components of the somatotropic axis are involved in regulating sleep quality. Although the roles of each hormone could not be identified, the findings of a recent study in transgenic mice with a deficiency in the somatotropic axis have been particularly convincing as a robust loss of non-REM sleep

Sleep Abnormalities in Conditions of Deficient or Excessive GH Secretion

A limited number of human studies, all originating from the same group of investigators, have examined sleep quality in subjects with congenital isolated GH-deficiency and in acromegalic patients before and after treatment (90). In GH-deficient adults, a decrease in duration of SW sleep and a significant suppression in delta power were observed but there were no significant differences in REM sleep (90,91). After six months of daily treatment with 2 IU m2 GH, the relative amount of REM sleep increased and there was a trend for an increased duration of SW sleep (92). In untreated acromegalic patients without sleep apnea, standard polysomnography revealed a reduction in REM sleep as well as a reduction in amount of SW sleep as compared to control subjects (92). However, a more complex picture emerged when power spectral analysis of the EEG was performed (92). Indeed, though the minutes of REM and SW were decreased, the spectral energy per min spent in both REM and SW was increased,...

Effects of Somatostatin on Sleep

Inconsistent data have been reported concerning the action of somatostatin on sleep. In the rodent, REM sleep was inhibited by immunoneutralization of endogenous soma-tostatin (111) and enhanced by intracerebroventricular administration of exogenous somatostatin (112), while non-REM sleep was inhibited by subcutaneous injections of a long-acting somatostatin analog (113). In humans, repeated intravenous injections or infusion of somatostatin did not influence sleep quality in normal young subjects (107,114), but REM sleep was decreased by somatostatin in the elderly (115).

Anxiety And Psychological Stress States

A randomised study found that low-dose valerian (100 mg) reduced situational anxiety without causing sedation (Kohnen & Oswald 1988). Positive results were also obtained in a smaller open study of 24 patients suffering from stress-induced insomnia who found treatment (valerian 600 mg day for 6 weeks) significantly reduced symptoms of stress and insomnia (Wheatley 2001). Another randomised trial compared the effects of a preparation of valepotriates (mean daily dose 81.3 mg) with diazepam (mean daily dose 6.5 mg) and placebo in 36 outpatients with GAD under double-blind conditions (Andreatini et al 2002). After 4 weeks' treatment, all groups had significant reductions in Hamilton anxiety (HAM-A) scale scores however, only those receiving valepotriates or diazepam showed a significant reduction in the psychic factor of HAM-A.

Substance abuse and related disorders

Symptoms may include increased heart rate, shaking, insomnia, fatigue, and irritability. The DSM-IV-TR does not recognize caffeine abuse or dependence, but does recognize the caffeine-induced disorders caffeine intoxication (restlessness, nervousness, excitement, etc. after caffeine consumption), caffeine-induced anxiety disorder (feelings of anxiety or panic attacks after caffeine consumption), and caffeine-induced sleep disorder (usually insomnia, but some may experience excessive sleepiness when caffeine is not consumed). As for nicotine, the DSM-IV-TR recognizes nicotine dependence and nicotine withdrawal.

Phenomenology Of Depression In Dementia

Chemerinski, Petracca, Sabe, Kremer, and Starkstein (2001) evaluated how well mood as rated by both caregiver and dementia patient accounted for depressive syndromes in 253 persons with AD, 47 persons with depression but no dementia, and 20 healthy controls. Depressed mood as rated by both caregivers and patients was a powerful predictor of a host of other depressive symptoms including apathy, anxiety, insomnia, loss of interest, agitation, and psychomotor retardation. These data further supported the importance of assessing mood in persons with dementia.

How long should treatment be continued

Benzodiazepines for anxiety and insomnia should be given for only a few weeks at a time, because of the risk of tolerance and dependence but antidepressants, if effective, should be continued for several months to prevent relapse. Lithium for prophylaxis of affective disorder, and antipsychotics for maintenance treatment of schizophrenia, are usually continued for several years and sometimes are needed for life.

Premenstrual Syndrome

Vitamin B6 supplementation is used in doses beyond RDI levels for the treatment of PMS. A 1999 systematic review of nine clinical trials involving 940 patients with PMS support this use, finding that doses up to 100 mg day are likely to be of benefit in treating symptoms and PMS-related depression (Wyatt etal 1999). Comparative study One randomised double-blind study compared the effects of pyridoxine (300 mg day), alprazolam (0.75 mg day), fluoxetine (10 mg day) or propranolol (20 mg day) in four groups of 30 women with severe PMS (Diegoli et al 1998). In this study, fluoxetine produced the best results (a mean reduction of 65.4 in symptoms) followed by propanolol (58.7 ), alprazolam (55.6 ), pyridoxine (45.3 ) and placebo (39.4-46.1 ). Symptoms responding well to pyridoxine were tachycardia, insomnia, acne and nausea (Diegoli et al 1998).

Clinical Aspects

Most inferences concerning pineal hormones and diseases have come from studies with experimental animals. Thus, pinealectomy at an early time in development in some species can lead to premature ovarian function, and treatment with melatonin can suppress ovarian function. As described earlier, the amounts of melatonin secreted nocturnally decline just prior to and during pubescence. Moreover, an acute oral dose (1-3 mg kg) given to young adults causes prolactin to be secreted. A number of different kinds of tumors can affect the function of the pineal gland, usually resulting in central nervous system disturbances and either premature or delayed gonadal functioning, especially when the tumors occur in the young. There may be a point of interaction above the pituitary between melatonin and ACTH-corticosteroid secretion. An acute lowering of Cortisol secretion in humans (by metyrapone, for instance) stimulates melatonin secretion. Melatonin also appears to inhibit the release of CRH,...

The Physiology Of Sleep And Its Aging

The sleep wake cycle and the 24-hour rhythm of the body temperature are regulated by a circadian periodicity that originates from the suprachiasmatic nucleus in the hypothalamus. In the morning we wake up, our body temperature increases from the nocturnal level, and we are able to be active throughout the day. In the late evening, when it is dark, we normally go to bed, and after a while we fall asleep. Stages 3 and 4 Referred to as deep sleep, delta sleep, or slow-wave sleep (SWS). Waking from these stages is more difficult than from stages 1 and 2. During SWS, growth hormone is released from the hypothalamus. Many restorative processes, such as healing of injuries and immunological processes necessary for defense against infections or malignancies are most active during SWS (Stanley, 2005). Stage 5 During rapid-eye-movement (REM) sleep, dreams are more common than in other sleep stages. REM sleep may occur in four or five periods throughout the night at intervals of 60 to 90 minutes...

Agerelated Development

The sleep pattern changes in parallel with aging. The time spent in deep sleep (slow-wave sleep) is decreased, and in the very elderly it may be absent. The number of awakenings increases with aging and in many elderly falling asleep after such awakenings becomes increasingly difficult. Elderly persons are therefore more troubled by spending time in the waking state in bed than younger adults. This decline in sleep maintenance is to some extent an expression of the age-related disorganization of the circadian sleep wake rhythm. However, sleep quality in the elderly seems to be more attributable to health-related factors than to age per se. In a study of the influence of somatic health, mental health and age on sleep in a group of elderly men and women, it was found that in men, more severe sleep disturbances were associated with poorer somatic health, poorer mental health, and increasing age, in that order of importance, and that in women, they were correspondingly associated with...

Sleep In Different Countries

The prevalence rates of sleep disturbances vary considerably between different countries of the world. In a recent review of the literature based on data collected in 50 community-dwelling populations, prevalence rates of insomnia ranging from less than 5 to 40 were reported (Ohayon, 2002). In a cross-sectional survey in 10 countries (Austria, Belgium, Brazil, China, Germany, Japan, Portugal, Slovakia, South Africa, and Spain), answers to a standardized questionnaire were collected from 35,327 men and women with mean age 39 years (7.9 of ages 65 years or older). In the whole study group ''not sleeping well'' was reported by the least proportion of respondents in Austria (10.4 ) and the highest proportion in Belgium (32.2 ). Correspondingly, the nocturnal sleep duration varied from 413 69 (mean standard deviation, SD) minutes in Japan to 504 89 minutes in Portugal, and the time taken to fall asleep varied from 15.2 18.4 minutes in Austria to 34.4 42.1 minutes in South Africa. Regular...

Somatic Diseases And Symptoms

Heart diseases and sleep disturbances interact with one another in a reciprocal and complicated way. In a classic study of Finnish adult men, Partinen and coworkers found a higher prevalence of coronary heart diseases in men who slept less than six hours per night after adjustment for age, sleep quality, use of sleeping pills and tranquilizers, smoking, alcohol use, Type A score, neuroticism, use of cardiovascular drugs, and history of hypertension. Difficulty in falling asleep at bedtime has been found to be associated with a two-fold increase in the risk of myocardial infarction during a follow-up period of 4.2 years (Appels and Schoulten, 1991). Further, among patients with myocardial infarction in another study, almost half had had sleep disorders during the six months immediately preceding the onset, which is a higher proportion than in a comparable population without myocardial infarction (Carney et al., 1990). Windows open more often -Easier to fall asleep -Fewer awakenings...

Psychiatric Diseases And Symptoms

Alzheimer's disease and other dementias Senile dementia of the Alzheimer's type (AD) is often associated with sleep impairment, and several kinds of disturbances have been described, such as reduction of sleep efficiency and of the total length of sleep. There is also a relationship between the severity of the sleep disturbance and the severity of the dementia. Patients with AD have an increased number and duration of awakenings, an increased percentage of stage 1 sleep, reduced slow-wave (deep) sleep, and reduced REM sleep (Petit et al., 2004). in AD differs from that of depression in showing a greater reduction of REM sleep and a lower REM density. The intellectual ability and the daytime performance may also be impaired by central sleep apnea, which is present in 33 to 53 of patients with AD (Asplund, 1999). Sleep problems are common in elderly persons with depressive disorders, and in the Diagnostic Statistical Manual (DSM-IV) of Mental Disorders, sleep deterioration is included...

Recommended Resources

Alessi, C.A., and Schnelle, J.F. (2000). Approach to sleep disorders in the nursing home setting. Sleep Med. Rev. 4, 45-56. Montgomery, P. and Dennis, J. (2004). A systematic review of non-pharmacological therapies for sleep problems in later life. Sleep Med. Rev. 8, 47-62. Ohayon, M.M. Relationship between chronic painful physical condition and insomnia. J. Psychosom. Res. 39, 151-159. Schwartz, S., Mcdowell-Anderson, W., Cole, S.R., Cornoni-Huntley, J., Hays, J.C., and Blazer, D. (1999). Insomnia and heart disease A review of epidemiologic studies. J. Psychosom. Res. 47, 313-333.

Effects on Sleep and Psychological Function

The frequency of sleep disorders increases markedly with aging. It has long been known that nocturnal secretion of GH is correlated with episodes of slow-wave (delta) sleep (SWS) but it is not clear whether this means only that SWS stimulates GH secretion, or whether the stimuli to GH secretion, such as GHRH, can also stimulate SWS. Kerkhofs and colleagues reported that GHRH could acutely promote sleep in normal men, with the specific effects depending upon the timing of drug administration (51). This topic is reviewed by Van Cauter and colleagues in this volume (Chapter 15).

Captivity and Posttraumatic Stress Disorder

In reaction to the mistreatment of prisoners of war during the nineteenth century, beginning in 1864 a series of international meetings known as the Geneva Convention was held. The result was a set of rules regarding the humane treatment of prisoners of war, as well as the sick, the wounded, and those who died in battle. Despite some improvements as a result of the Geneva Convention and the rules for the treatment of prisoners of war that were defined at the Second Hague Conference of 1907, the conditions under which prisoners existed continued to be atrocious in many instances. During World War II for example, American soldiers captured by the Japanese were subjected to inhuman treatment and forced to survive on a near-starvation diet. In many ways, however, American soldiers who were taken prisoner by the Viet Cong or North Vietnamese during the Vietnam War suffered an even worse fate. Reminiscent of the treatment of inmates in concentration camps during World War 11, prisoners in...

Reasons For Noncompliance

Plegia have all been cited as reasons for noncompliance.14 Falling asleep prior to bedtime medications or being unable to walk independently to the kitchen to use refrigerated drops can interfere with drug administration. Other physical hindrances to compliance with eye drops include difficulties with positioning the head, aiming the dropper bottle, and squeezing the bottle. Kass et al.23 found that 20 of patients relied on another person to administer their eye drops. Winfield et al.9 evaluated 200 patients who were prescribed eye drops for various reasons, including glaucoma 57 of these patients admitted difficulty administering their drops, and when directly observed, only 20 instilled a drop correctly on the first try. In another study, 27 of patients were unable to put drops into each eye on the initial attempt Uniform teaching of drop administration was correlated with an increase in the patients' ability to instill eye drops properly.8 These studies reinforce the idea that...

Premenstrual Dysphoric Disorder

Premenstrual dysphoric disorder (PMDD) is characterized by markedly depressed mood, anxiety, affective lability, and decreased interest in daily activities during the last week of luteal phase in menstrual cycles of the last year. In 2002, Atmaca et al. conducted an 8-week, randomized, single-blind, rater-blinded, prospective- and parallel-group, flexible-dosing trial to compare the efficacy of fluoxetine with V. agnus-castus for the treatment of PMDD in 42 females. Both fluoxetine and V. agnus-castus had dose ranges from 20 to 40 mg. Outcome measures included the Penn daily symptom report, Hamilton depression rating scale, clinical global impression (CGI)-severity of illness scale, and CGI-improvement scale. Both drugs were well tolerated. No statistically significant differences between groups were found. The authors concluded that fluoxetine was more effective (a decrease of more than 50 in rating symptoms) for psychological symptoms (depression, irritability, insomnia,...

Hypnopompic hallucinations

A sensory perception that seems real to the person but that arises without external stimulus. It may occur in any sensory modality. Visual ones suggest organic states auditory ones, mental illness, especially schizophrenia. False perceptions can occur while falling asleep (hypnagogic), dreaming, or awakening (hypnopompic), but these would not usually be termed hallucinations.

GRAFS Classification of 7TMRs

Grafs Classification

The rhodopsin segment of the GRAFS classification now includes the 460 or so olfactory receptors in the classical family A. Fredriksson and coauthors8 identified four rhodopsin subfamilies designated a, p, g, and d (Figure 10.2). The a subfamily of rhodopsin receptors includes a prostaglandin, a monoamine, an opsin, and a melatonin receptor cluster. A fifth more diverse cluster incorporates the adenosine and cannabinoid receptors as well as the Edg receptors for charged lipids and the melanocortin receptors that bind a tridecapeptide. The p subfamily includes the major peptide hormones of the hypothalamus, pituitary, and digestive tract. The g

Pharmacological Toxicological Effects

14 females were given 300 mg Hypericum three times daily for 4 weeks, given a 2-week washout period, then given placebo for 4 weeks. The continuity of sleep, onset of sleep, intermittent wake-up phases, and total sleep were not improved. There was, however, a significant increase in deep sleep (stage 3 and 4, slow wave) that was shown by analysis of electroencephalogram activities (23). Thus, Hypericum may be able to improve sleep quality.

Health Precautions For Researchers Handling Bats

Symptoms of rabies usually develop 10-14 days after exposure and include pain, burning and numbness at the site of infection, headaches, insomnia, fever, and difficulty swallowing. However, usually by the time the symptoms are apparent, the progression of the disease can no longer be prevented, ultimately resulting in fatal inflammation of the brain and spinal cord. Therefore, it is imperative that a person seek immediate medical attention after any potential exposure. People handling bats should obtain pre-exposure immunization, which is conferred by 3 doses of vaccine, and check their titers regularly. Additionally, they should simply avoid exposure. Bats captured to establish a captive colony should be quarantined for at least 6 months to assess possible sickness. Always wear gloves when handling bats and avoid rapid and unpredictable movements which increase the chance of bites.


The use of medications in the treatment of depression began in the late 1950s with the successful introduction of tricyclic antidepressants and MAO inhibitors. Treatment of depression with medications has greatly increased since the advent of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline (Zoloft). While these medications are no more effective than their predecessors, they have fewer side effects and are much safer for patients who may be likely to overdose. Selecting the optimal antidepressant medication is not always a straightforward process, however, and the patient may have to try out various drugs for a period of weeks or months before finding one that is effective for him or her. In addition, while the SSRIs have comparatively few side effects, such complaints as loss of sexual interest or functioning, nervousness, headaches, gastrointestinal complaints, drowsiness, and insomnia can be significant obstacles to the patient's taking the...

Concluding Remarks

GSK-3 a and p have a plethora of functions that complicate assessment of these molecules as a target for therapy. There are multiple important pathological conditions in which GSK-3 is dysregulated including neurological disorders such as bipolar disorder, sleep disorders, Alzheimer's disease, and T2DM. In each of these conditions, inhibition of GSK-3 should provide relief of the driving forces of the diseases. The major concern, however, is that chronic inhibition of GSK-3 can also lead to activation of targets that are proliferative such as certain transcription factors and p-catenin, which is a human oncogene. To counter this concern, there are indications that the levels of inhibition required for effects on metabolic or neurological behaviors are much lower than required for stabilization and activation of p-catenin. Only 25 inhibition of total GSK-3 (as achieved in mice heterozygous for GSK-3P) is sufficient to phenocopy behavioral effects of lithium treatment in mice and to...


Features of the third stage include significant feelings of apathy and depression. This phase takes a year or more. Physical illness is common and includes problems such as insomnia, asthma, bowel dysfunction, headache and appetite disturbances.


Relaxation has been used to help women during childbirth and people with chronic pain. Relaxation has also been used to treat muscle tension, muscle spasms, neck and back pain, and to decrease perspiration and respiratory rates. Furthermore, relaxation can help with fatigue, depression, insomnia, irritable bowel syndrome, high blood pressure, mild phobias, and stuttering.


Sleep disorders related to PD are multifactorial, and the causation is complex and largely unknown. Degeneration of central sleep regulatory neurons either due to a direct or an indirect effect of dopaminergic cell loss in the brainstem and related thalamo-cortical pathways, is implicated (17,19,20). A preclinical pathological staging of PD has been proposed by Braak (21). It has been traditionally believed that the pathological process of degeneration of dopaminergic neurons starts in the sub-stantia nigra however, Braak (21) proposed an alternative, as he has introduced the concept of a six-stage pathological process, beginning at clearly designated induction sites. In Braak stage 1 of PD, there is degeneration of the olfactory bulb and the anterior olfactory nucleus, which may clinically manifest as olfactory dysfunction. Progression of the pathological process to the lower brainstem occurs in Braak stage 2, which are key areas mediating nonmotor symptoms such as olfaction, sleep...


There is a poor evidence base for the treatment of sleep problems in PD, and the issue is complicated by the fact that treatment of sleep problems in PD needs to take into account the multifactorial nature of sleep disturbances in PD. A review by the Movement Disorder Society Task Force reported that there were no robust trials of dopaminergic agents for the treatment of nonmotor symptoms in PD, including sleep (80). Only modafinil (for EDS) and melatonin (for insomnia) have been studied in randomized, double-blind trials in a small number of patients with PD (Table 6). Other published reports consist of case series and open-label trials with limited and inadequate evidence for treatment. Insomnia-related symptoms Fragmented sleep with difficulty in sleep onset and sleep maintenance Nonpharmacologic measures Avoidance of nighttime alcohol, caffeine, tobacco Increase in daytime physical activity and ensuring exposure to daylight Psychological therapies relaxation training, cognitive...


Sleep disorders in patients with PD are common (94). They are a key component of the nonmotor symptom complex of PD and remain under-diagnosed and under-treated. Sleep problems may arise from uncontrolled motor symptoms, degeneration of the neuroanatomical substrates responsible for the sleep-wake cycle or unwanted medication side effects. Routine assessment of patients with PD should include inquiry regarding the quality of sleep and sleep-related symptoms. Use of validated bedside clinical tools such as the PDSS, SCOPA-Sleep, and ESS offer a robust way to assess the presence or absence of sleep disruption. Uncontrolled nocturnal motor symptoms may be ameliorated by long-acting dopaminergic agents, whereas other sleep disruptions such as hallucinations or RBD require a different approach. In resistant cases, patients may need to undergo a formal sleep study with PSG and or MSLT. Targeted nighttime treatment should result in improved sleep for patients with PD.


Alcohol appears to at least add to the hypnotic effect of kava in mice, and was also observed to increase the lethality of kava (37). These findings may be of importance because some Australian Aboriginal populations now frequently consume kava with alcohol. Concomitant use of barbiturates, melatonin, and other psychopharmacological agents might potentiate the effects of kava as well (38). The hepatotoxic potential of kava (27) also raises concerns about concomitant alcohol use.


Explain tactfully that since there is no clinical evidence of inflammation, his NSAIDs can be ceased. Because he is depressed with an anxiety component and insomnia, an antidepressant can be prescribed to be taken at night ( click here for an explanation for the patient). He can be assured that not only will this help his psychological state but it should help 'shut the pain pathway gate' and reverse the overactivity of the nervous system.

Brian J Isetts

Valerian is a unique herb with a long history of use through western Europe as a sedative and hypnotic. A variety of pharmacologically active components are likely responsible for its clinical effects including volatile oils, monoterpenes, valepotriates, and sesquiterpenes. Valerenic acid, a sesquiterpene component of valerian, is postulated to produce sedation through inhibition of the breakdown of gamma-amino butyric acid. The herb is well tolerated, and side effects have been mild and self-limiting in most cases. Isolated reports of liver damage have occurred with valerian being a concomitantly consumed agent, yet anecdotal cases of attempted intentional self-poisoning with the herb have not resulted in fatality and long-term follow-up for subsequent hepatotoxicity in a number of these patients has not revealed liver abnormalities. The herb's postitive safety profile and demonstrated effectiveness in treating insomnia contributes to its popularity.

The Parasomnias

REM sleep behavior disorder (RBD) was first reported by Schenck et al. in 1986 and is a parasomnia, which is typically characterized by vivid and usually frightening dreams or nightmares associated with a paradoxical simple or complex movement during REM sleep when muscles are usually atonic (13,23). RBD is thought to have a population prevalence of 0.5 . During REM sleep, patients enact their dreams, which can be vivid or unpleasant, and partners report vocalizations (talking, shouting, vocal threats) and abnormal movements (arm leg jerks, falling out of bed, violent assaults) (35-40). Typical clinical features of RBD are summarized in Table 3. Although clinical history may suggest a diagnosis, in some situations such as when there is a high risk of physical injury or loud snoring suggestive of obstructive sleep apnea, confirmation of diagnosis should be obtained by a single night of polysomnography (PSG) with video telemetry. PSG would show an increased electromyographic (EMG)...


Buspirone's actions are different from a common class of sedatives called benzodiazepines. The primary action of benzodiazepines is to reduce anxiety, relax skeletal muscles, and induce sleep. The earliest drugs in this class were chlordiazepoxide (Librium) and diazepam (Valium). Buspirone also acts through a different mechanism than barbiturates such as phenobarbital. Unlike benzodiazepines, buspirone has no anticon-vulsant or muscle-relaxant properties, and unlike benzodiazepines or barbiturates, it does not have strong sedative properties. If insomnia is a component of the patient's anxiety disorder, a sedative hypnotic drug may be taken along with buspirone at bedtime. Buspirone also diminishes anger and hostility for most people. Unlike benzodiazepines, which may aggravate anger and hostility in some patients, (especially older patients), bus-pirone may help patients with anxiety who also have a history of aggression. The most common side effects associated with bus-pirone...

Adjustment disorders

Adjustment disorders are maladaptive reactions to psychosocial stress, lasting no more than about 6 months. Common symptoms include anxiety, depression, insomnia, behavioural changes, and physical complaints. These symptoms appear in excess of the 'normal' reaction to the stressor concerned, and produce some impairment of occupational and social function. Counselling or social casework is usually considered more appropriate than drugs, although some patients do benefit from antidepressants or anxiolytics.


Synthesis of S-adenosyl-L-methionine (SAMe) A THF derivative is critical for the regeneration of methionine from homocysteine. The methyl group donated in this process is taken up by SAMe, which provides it with the ability to become a carbon donor in multiple transmethylation reactions throughout the body including the synthesis of adrenaline, melatonin and creatine (Hendler & Rorvik 2001). Amino acid metabolism Folate is involved in the synthesis of some of the nonessential amino acids such as serine and glycine. It is also required for the conversion of histidine into glutamate (Gropper et al 2005).


Dida but also Pneumocistis carini especially for those also on chemotherapy), thinning of skin, increased bruising, peripheral edema, vascular bone necrosis, insomnia, irritability, acne, cushingoid state, hypertension, and proximal myopathy (45). Many ofthese effects are reversible with steroid reduction but they can cause serious quality of life issues. Because DMS has a long half-life, we generally recommend morning loading when possible to lessen some of the night-time side effects such as insomnia (i.e., for bid dosing we would recommend taking medication at breakfast and lunch instead of 8 am and 8 pm). For steroid weaning we generally decrease DMS by 2 mg every 4 d as tolerated. It is important to emphasize to patients that steroid dosing is a mix of an art and science and that good doctor patient communication will allow the best care.

Quality Of Life

A double-blind, placebo-controlled crossover study found that 1200 mg ginseng was only slightly more effective than placebo and not as effective as a good night's sleep In Improving bodily feelings, mood and fatigue In 12 fatigued night nurses. Volunteers slept less and experienced less fatigue but rated sleep quality worse after ginseng administration (Hallstrom et al 1982).

Types of Sleep

The two types of normal sleep are slow wave and rapid eye movement (REM). Slow-wave sleep (also called non-REM sleep) occurs when a person is very tired, and it reflects decreasing activity of the reticular formation. It is restful, dreamless, and accompanied by reduced blood Fatal familial insomnia Inability to sleep, emotional instability, hallucinations, stupor, coma, death within thirteen months of onset around age fifty, both slow-wave and REM sleep abolished. Insomnia Abnormal REM sleep causes extreme daytime sleepiness, begins between ages of fifteen and twenty-five. REM-sleep behavior disorder Excessive motor activity during REM sleep, which disturbs continuous sleep. Inability to move for up to a few minutes after awakening or when falling asleep. pressure and respiratory rate. Slow-wave sleep may range from light to heavy and is usually described in four stages. It may last from seventy to ninety minutes. Slow-wave and REM sleep alternate. REM sleep is also called...

Affective Disorders

Feelings of intense sadness, hopelessness, pessimism, low self-esteem, loss of appetite and interest, insomnia, fatigue, aches and pains, and memory problems that are symptomatic of depression can also occur as a reaction to the loss of a loved one, physical disorders, financial insecurity, social isolation, or any other serious problem. Unlike psychotic depression, in which guilt, self-deprecation, and bodily complaints are extreme and grossly unrealistic, the apathy, inertia, and withdrawal seen in neurotic or reactive depression are less bizarre and more closely associated with external circumstances.

Activity Rhythms

Approximately 40-70 of elderly people suffer from some type of sleep disorder such as increased waking at night or frequent napping during the day (Van Someren, 2000). These effects are exacerbated in subjects with dementia (Satlin et al., 1991). We have assessed the circadian pattern of locomotor activity in dogs with the Actiwatch actigraph monitoring system (Siwak et al., 2003). Dogs exhibit clear activity-rest rhythms in which activity levels are high during the day and low at night. Moreover, circadian patterns of locomotor activity in dogs exhibit age-related alterations, which vary with cognitive status and housing environment.


A checklist of pointers to the adverse effects of chronic alcohol abuse is presented in Table 18.1 . In a study by the author the outstanding clinical problems are the psychogenic disorders (anxiety, depression and insomnia) and hypertension. 4 Susceptibility to work and domestic accidents were also significant findings. insomnia nightmares

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