Total Sleep Time

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. 

Zaleplon also binds to the GABAa receptor. It has a rapid onset, a half-life of about 1 hour, and no active metabolites. It does not reduce nighttime awakenings or increase the total sleep time. It may be best used for middle-of-the-night awakenings. It does not appear to cause significant rebound insomnia or next-day psychomotor impairment. The most common side effects are dizziness, headache, and somnolence. The recommended dose is 10 mg (5 mg in the elderly). 

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]. 

In controlled clinical trials in patients with primary insomnia, ramelteon 4-32 mg demonstrated significant reduction in latency to persistent sleep (LPS) compared with placebo. In elderly patients, objective and subjective LPS were also reduced at doses of 4 and 8 mg. Data on total sleep time are more variable,... 

Clinical results with 20 have been recently reported from a phase I study that enrolled 70 healthy male human subjects. In this study, morning administration of the drug (200 mg and above) reduced alertness and latency to sleep stage 2 and increased time spent in sleep stage 2 with an overall improvement of sleep efficiency and total sleep time. These effects disappeared 6.5 h after drug administration [57],... 

Caffeine and theophylline decrease total sleep time, time spent in SWS and REM sleep and increase the number of intrasleep arousals. Withdrawal of caffeine in regular users leads to daytime sleepiness, increased slow wave (delta) activity on the EEC and headaches. The mechanism of action appears to be antagonism of central adenosine Ai and A2 receptors which normally exert a CNS depressant action, with consequent interference with the sleep-inducing action of adenosine (Chapter 6). 

Eszopiclone has been approved for the treatment of patients who experience difficulty falling asleep, poor sleep maintenance, and for long-term treatment of insomnia. Clinical trials have shown that eszopiclone improved sleep onset, sleep maintenance, total sleep time, sleep quality, and daytime functioning compared with placebo. Improved wake time alertness, concentration, and sense of well-being were reported. Eszopiclone was well tolerated, with only mild adverse events reported. There was no evidence of dmg-drug interactions, tolerance, residual drowsiness or treatment-related rebound insomnia. The recommended dose to improve sleep onset and maintenance is generally between 1 and 3 mg. 

The effects on sleep are a decrease of sleep latency, a diminished number of awakenings with, as an overall effect an increase in total sleep time. However in many patients partial tolerance to the effects on sleep develop in a few nights. 

Figure 3.7 Effects of /-amphetamine on polygraphic sleep stages. A decrease in REM sleep, an increase in sleep unrest (shifts from sleep stages 2, 3 and 4 into the waking state and into stage 1) and an increase in stage 1 are typical effects seen after amphetamine-like stimulants used at small doses. After larger doses REM sleep is even more markedly reduced and total sleep time (TST) is shortened (reproduced from Spiegel, 1982, with permission from S. KargerAG, Basel)...

Research in depression (e.g., REM density and latency total sleep time)... 

A decreased need for sleep is a frequent prodromal sign and is characterized by early awakening (sometimes by several hours), a significant reduction in total sleep time, and when severe, several sleepless days with no apparent fatigue. 

Patients older than 65 years of age tend to suffer from sleep maintenance insomnia melatonin serum levels have been reported to be low in these patients. Elderly patients with sleep maintenance insomnia who received immediate-release and sustained-release melatonin had improved sleep onset time. They did not, however, experience an improvement in sleep maintenance or total sleep time. 

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

The effects of various time-in-bed (TIB) conditions on daytime sleepiness and total sleep time (during a 24-hr enforced bedtime) were investigated by Rosenthal et al. (29). Thirty-two subjects were randomly assigned to spend 8, 6,... 

Rosenthal L, Roehrs TA, Rosen A, Roth T. Level of sleepiness and total sleep time following various time in bed conditions. Sleep 1993 16(3) 226-232. 

Treatment will call upon dopamine agonists, opioid medications, a benzodiazepine (clonazepam) that increases total sleep time, and drugs most commonly used as antiepileptic medication, such as gabapentin or equivalent. Dopamine agonists are the most effective and reduce the sleep deprivation and the patients complaints. But not all patients respond to dopamine agonists and methadone has been prescribed in the most refractory cases (21). 

Further disruption of REM sleep is related to the presence of hallucinations and REM sleep behavior disorder in Parkinson s patients. A decrease in REM sleep has been associated with nocturnal hallucinations (125), and REM intrusion during daytime hallucinations has been reported (126). More than one third of Parkinson s patients also suffer from REM sleep behavior disorder (RBD) (127,128) or REM sleep without atonia (128). In these patients, there is also a significant reduction in total sleep time. In many cases RBD is diagnosed several years prior to the onset of Parkinson s disease (129), although a link between disease severity and duration and the presence of RBD has also been reported (128). RBD is most often treated with the administration of clonazepam (104,129). Patients with comorbid dementia and depression also experience a high level of sleep disturbance, associated with nocturnal vocalizations and hallucinations (130). One side effect of many antidepressant medications, however, is insomnia and sleep disturbance (131). 

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