Sleep latency

BzRAs significantly reduce sleep latency and the number and duration of awakenings, resulting in increased total sleep and improved sleep continuity. 

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. 

Antihistamines such as diphenhydramine are known for their sedating properties and are frequently used over-the-counter medications (usual doses 25-50 mg) for difficulty sleeping. Diphenhydramine is approved by the FDA for the treatment of insomnia and can be effective at reducing sleep latency and increasing sleep time.43 However, diphenhydramine produces undesirable anticholinergic effects and carryover sedation that limit its use. As with TCAs and BZDRAs, diphenhydramine should be used with caution in the elderly. Valerian root is an herbal sleep remedy that has inconsistent effects on sleep but may reduce sleep latency and efficiency at commonly used doses of 400 to 900 mg valerian extract. Ramelteon, a new melatonin receptor agonist, is indicated for insomnia characterized by difficulty with sleep onset. The recommended dose is 8 mg at bedtime. Ramelteon is not a controlled substance and thus may be a viable option for patients with a history of substance abuse. 

Melatonin at doses of 0.5 to 5 mg taken at appropriate target bedtimes for east or west travel is becoming the drug of choice for jet lag. Melatonin significantly reduces jet lag and shortens sleep latency in travelers.50 Hypnotic agents with relatively short durations of action (3 to 5 hours) also may be used to sustain sleep during the initial adaptation to the new time zone. 

Evaluate improvement in the specific sleep complaint (e.g., how has therapy affected sleep latency ). 

MSLT multiple sleep latency test KEY REFERENCES AND READINGS... 

Sleep latency The amount of time it takes to fall asleep. 

Gilbert, S. S., VandenHeuvel, C. J. 8r Dawson, D. (1999). Daytime melatonin and temazepam in young adult humans equivalent effects on sleep latency and body temperatures. J. Physiol. Lond. 514, 905 14. 

Held, K Antonijevic, I., Murck, H., Kuenzel, H. Steiger, A. (2006). Neuropeptide Y (NPY) shortens sleep latency but does not suppress ACTH and cortisol in depressed patients and normal controls. Psychoneuroendocrinology 31, 100-7. 

Inability to maintain wakefulness bouts Severe decrease in REM sleep latency Frequent cataplexy and direct transitions to REM sleep... 

Mild decrease in REM sleep latency Absence of cataplexy or direct transitions to REM sleep Inability to maintain wakefulness bouts Mild decrease in REM sleep latency Occasional cataplexy and direct transitions to REM sleep Inability to maintain wakefulness bouts Severe decrease in REM sleep latency Frequent cataplexy and direct transitions to REM sleep Inability to maintain wakefulness bouts Severe decrease in REM sleep latency Frequent cataplexy and direct transitions to REM sleep Inability to maintain wakefulness bouts Severe decrease in REM latency Frequent cataplexy and separable direct transitions to REM sleep... 

Characterization of the receptor knockout mice (OXjR / and 0X2R l ) provided important information about the differential roles of the two receptors in both vigilance state control and the symptoms of narcolepsy (Kisanuki et al., 2000 Willie et al., 2003). In contrast to the direct transitions to REM sleep and abrupt behavioral arrests that characterized orexin mice, 0X,R l mice exhibited no direct transitions to REM sleep and only a modest decrease in REM sleep latency (Kisanuki et al, 2000). 0XiR / mice also showed slight fragmentation of vigilance states when compared with the normal animals (Kisanuki et al., 2000). 

Figure 15.7 Normalized REM sleep latency histograms, expressed as a percentage of all REM sleep episodes, for the orexin and orexin mice under normally...

BZD effects on human sleep are well characterized (Mendelson 2001) (a) decreased sleep latency (b) decreased awakenings (c) increased stage II sleep (d) suppressed stage III and IV sleep (e) increased REM sleep latency (f) initial reduction and fragmentation of REM sleep. Discontinuation of BZD treatment after three to four weeks produces a rebound of REM sleep as well as slow-wave sleep (SWS). BZD and non-BZD compounds are pharmacological agents indicated in the management of anxiety, insomnia, and other conditions in which anxiety is the main symptom, and should be considered as symptomatic medications (Nishino et al. 2004). 

The median values of REM sleep latency, total time asleep, and SWS (in minutes and as a percentage of total time asleep) were lower, and REM sleep (percent) values were found to be higher, in depressive disorders than in all other psychiatric conditions. However, the statistical differences between depressed patients and other psychiatric categories were far less evident. Indeed, no sleep variable reliably distinguished depressed patients from those with other psychiatric disorders. The investigators concluded that sleep disturbances are associated with most psychiatric disorders, although the most widespread and most severe disturbances are found in patients with depressive disorders (Van Bemmel 1997). 

Winokur et al. (Winokur et al. 2000) found that mirtazapine significantly decreased sleep latency and increased total sleep time and sleep efficiency from baseline levels during week 1, with similar results observed after week 2. Mirtazapine did not significantly alter REM sleep parameters. Clinically, the Hamilton Depression Rating Scale and sleep disturbance ratings improved after treatment. 

In rats, cocaine (6 mg/kg, i.p. or p.o.) has been shown to induce a significant increase in sleep latency and a reduction in total sleep time, including a decrease in both non-REM sleep and REM sleep (Schwartz 2004). In humans, cocaine, amphetamines, and methylphenidate also produce decreases in sleepiness, an increased latency to sleep, and a marked decrease in REM sleep associated with an increased latency to the onset of this state. Amphetamine, methylphenidate, and cocaine are known to act by enhancing the amount of the monoamines available within the synaptic cleft of synapses in the CNS. 

Eszopiclone, the latest approved Z-drug, in a 6-month study in patients with chronic insomnia and following studies to 12 months, demonstrated significant decrease of sleep latency and awakenings and improvement in total sleep time. Importantly, daytime function and alertness were not affected, nor was there evidence of tolerance [15]. 

Valerian root, an over-the-counter herbal supplement, has also been used for insomnia. Thought to act, like the benzodiazepines, by increasing the activity of the neurotransmitter GABA, preliminary studies indicate that 400 mg of valerian root decreases sleep latency and enhances sleep quality. 

Take zaleplon immediately before bedtime or after going to bed and experiencing difficulty falling asleep. Taking it with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of zaleplon on sleep latency. 

---