Sleepiness, excessive daytime

Treatment of excessive daytime sleepiness in narcolepsy and other sleep disorders may require the use of sustained- and immediate-release stimulants to effectively promote wakefulness throughout the day and at key times that require alertness. 

Poor sleep architecture and fragmented sleep secondary to OSA can cause excessive daytime sleepiness (EDS) and neu-rocognitive deficits. These sequelae can affect quality of life and work performance and may be linked to occupational and motor vehicle accidents. OSA is also associated with systemic disease such as hypertension, heart failure, and stroke.21-23 OSA is likely an independent risk factor for the development of hypertension.24 Further, when hypertension is present, it is often resistant to antihypertensive therapy. Fatal and non-fatal cardiovascular events are two- to threefold higher in male patients with severe OSA.25 OSA is associated with or aggravates biomarkers for cardiovascular disease, including C-reactive protein and leptin.26,27 Patients with sleep apnea often are obese and maybe predisposed to weight gain. Hence, obesity may further contribute to cardiovascular disease in this patient population. 

FIGURE 38-1. Primary assessment and initial treatment for complaint of excessive daytime sleepiness. RLS, restless-legs syndrome NPSG, nocturnal polysomnography OSA, obstructive sleep apnea DA, dopamine agonist MSLT, multiple sleep latency test BZDRA, benzodiazepine receptor agonist SNRI, serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressant CPAP, continuous positive airway pressure. 

EDS excessive daytime sleepiness Log into the website www.pharmacotherapyprinciples.com... 

The sleep disorder narcolepsy, which affects around 1 in every 2000 people, is characterized by a tetrad of symptoms excessive daytime sleepiness, cataplexy (loss of muscle tone triggered by emotional arousal), hypnagogic hallucinations,... 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Sleep-wake state alterations in PD can be broadly classified into disturbances of (1) thalamocortical arousal state and (2) excessive nocturnal movement (Rye and Bliwise 2004 Rye and Iranzo 2005). The former includes the loss of sleep spindles and SWS, daytime sleepiness, and intrusion of REM sleep into daytime naps (i.e. sleep onset REM periods, or SOREMs), and the latter encompass periodic leg movements of sleep (PLMs) and REM sleep behavior disorder (RBD). The pathophysiological basis of sleepiness and SOREMs appears to be dopaminergic cell loss in PD, though excessive nocturnal movements are not as clearly related to dopaminergic deficits. 

Arnulf I. (2005). Excessive daytime sleepiness in parkinsonism. Sleep Med. Rev. 9, 185-200. 

Baumann C., Dauvilliers Y., Mignot E., Bassetti C. (2004). Normal CSF hypocretin-1 (orexin A) levels in dementia with Lewy bodies associated with excessive daytime sleepiness. Eur. Neurol. 52, 73-6. 

Parkinsonism with excessive daytime sleepiness - a narcolepsy like disorder ... 

Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease. JAMA 287(4), 455-63. 

Overeem S., van Hilten J. J., Ripley B., Mignot E., Nishino S., Lammers G. J. (2002). Normal hypocretin-1 levels in Parkinson s disease patients with excessive daytime sleepiness. Neurology 58(3), 465-8. 

Rye D. (2006). Excessive daytime sleepiness and unintended sleep in Parkinson s disease. Curr. Neurol. Neurosci. Rep. 6, 169-76. 

Schapira A. (2004). Excessive daytime sleepiness in Parkinson s disease. Neurology 63(8 Suppl. 3), S24-7. 

Excessive daytime sleepiness, the irresistible need for sleep during the day, is associated with a chronically low level of alertness. The term sleep attack describes these unavoidable brief naps. Cataplexy, an abrupt decrease or loss in... 

Excessive daytime sleepiness and sleep attacks Very high (95) Very low (5) Wide differential diagnosis for this complaint Diagnosed clinically very disabling symptom... 

The second constellation of narcoleptic symptoms can be summarized under the rubric of excessive daytime sleepiness, or an inability to regulate wakefulness. As recently reviewed by Mochizuki et al. (2004), at least four explanations have to date been proposed for this sleepiness a deficit in arousal, an impaired circadian alertness signal, abnormal homeostatic regulation of non-REM sleep, and excessive vigilance state fragmentation. These mechanisms are not mutually exclusive, and there are possible roles for orexin signaling in each of them, as we review in the following sections. 

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

OSA patients usually complain of excessive daytime sleepiness. Other symptoms are morning headache, poor memory, and irritability. 

The essential features are sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. Individuals with narcolepsy complain of excessive daytime sleepiness, sleep attacks that last up to 30 minutes, fatigue, impaired performance, and disturbed nighttime sleep. They have multiple arousals during the night. 

Medications used to treat narcolepsy are shown in Table 72-5. Pharmacotherapy focuses on excessive daytime sleepiness and cataplexy. 

Modafinil is considered the standard for treatment of excessive daytime sleepiness. Plasma concentrations peak in 2 to 4 hours, and the half-life is 15 hours. Preliminary evidence suggests no tolerance or withdrawal after abrupt discontinuation and no risk of abuse. 

Sodium oxybate (yhydroxybutyrate a potent sedative-hypnotic) improves excessive daytime sleepiness and decreases episodes of sleep paralysis, cataplexy, and hypnagogic hallucinations. It is taken at bedtime and repeated 2.5 to 4 hours later. Side effects include nausea, somnolence, confusion, dizziness, and incontinence. 

Other Hypersomnias. Narcolepsy is not the only hypersomnia, but it is by far the most common. Primary hypersomnia shares sleep attacks and excessive daytime sleepiness with narcolepsy but does not feature cataplexy or REM-associated abnormalities. Another rare hypersomnia is Kleine-Levin syndrome (KLS), which most often occurs in teenage boys. KLS consists of intermittent bouts of hypersomnia and bizarre behaviors including compulsive eating and sexual inappropriateness. Distinguishing these hypersomnias from narcolepsy may help clarify the patient s prognosis, but the treatment alternatives are very similar. 

Baneijee D, Vitiello MV, Grunstein RR. Pharmacotherapy for excessive daytime sleepiness. Sleep Med Rev 2004 8 339-354. 

Narcolepsy To improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. 

In addition, daytime sleep disorders are common in PD. Mild daytime somnolence and a need for a short nap is common in healthy elderly people. However, Tandberg et ah (1999) reported significantly more excessive daytime sleepiness, (defined as falling asleep three times or more a day or total daytime sleeping more than 2 hours) in PD patients (16%) than healthy elderly controls (1%). This disorder was more common in PD patients with more severe parkinsonism, cognitive impairment and hallucinations. 

Some stimulants are approved for treatment of narcolepsy. Stimulants mainly improve excessive daytime sleepiness, and the effects may be dose related (Mitler et al. 1990). However, cataplexy usually does not respond to stimulants (Hyman et al. 1995). Stimulants are often administered in divided daily doses, and doses are often titrated weekly on the basis of clinical response. 

Broughton RJ, Fleming JA, George CF, et al Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49 444-451, 1997... 

Mitler MM, Harsh J, Hirshkowitz M, et al Long-term efficacy and safety of modafinil (Provigil) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 1 231-243, 2000... 

These disorders are characterized by excessive daytime sleepiness for at least 1 month. The daytime sleepiness (falling asleep easily and unintentionally) is not accounted for by an inadequate amount of nighttime sleep. Another criteria is the presence of hypersomnia nearly every day for at least 1 month or episodically for longer periods of time, resulting in occupational or social impairment. 

Typical complications include insomnia and excessive daytime sleepiness due to frequent nighttime awakenings. Sleep electroencephalogram (EEG) reveals absent or decreased slow-wave sleep, and, in some patients, early-onset REM sleep. If untreated, long-term effects of sleep apnea include increased incidence of hypertension vascular events (e.g., myocardial infarction, stroke) poor work performance increased risk of traffic accidents and stress in personal relationships ( 22, 23). 

Persons with cognitive decline may respond to rivastigmine (1.5-6 mg twice daily), memantine (5-10 mg daily), or donepezil (5-10 mg daily) (see Chapter 60) affective disorders to antidepressants or anxiolytic agents (see Chapter 30) excessive daytime sleepiness to modafinil (100-400 mg in the morning) (see Chapter 9), and bladder and bowel disorders to appropriate symptomatic therapy (see Chapter 8). 

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