Daytime sleepiness

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. 

Evaluate CPAP therapy annually or at any time individuals experience symptoms (e.g., daytime sleepiness) despite CPAP therapy. For example, change in pressure settings to alleviate OSA may be needed if weight gain occurs. 

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. 

In rats, lesions targeting presumptively wake-active dopaminergic neurons that extend dorsally from the VTA into the ventral periaqueductal gray have recently been shown to result in c. 20% reductions in wakefulness (Lu et al. 2006). Daytime sleepiness and SOREMs were reported in a non-human primate following systemic delivery of the dopamine neurotoxin MPTP (Daley et al. 1999), and this was subsequently confirmed in two additional animals (Daley... 

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., Daley J., Freeman A., Bliwise D. (2003). Daytime sleepiness and sleep attacks in idiopathic parkinson s disease. In Bedard M-A., Agid Y., Chouinard S. et al. editors. Mental and Behavioral Dysfunction in Movement Disorders. Totawa, NJ Humana Press pp. 527-38. 

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. 

Stevens S., Cornelia C., Stepanski E. (2004). Daytime sleepiness and alertness in patients with Parkinson disease. Sleep 27, 967-72. 

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. 

Schwartz J. R. (2004). Pharmacologic management of daytime sleepiness. J. Clin. Psychiatry 65(Suppl. 16), 46-9. 

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. 

Modafinil is approved by the FDA to improve wakefulness in those who have residual daytime sleepiness while treated with PAP. It should be used only after patients are using optimal PAP therapy to alleviate sleep-disordered breathing. 

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