Sleep time

Gupta PK, Gupta RC. 1977b. Influences of endosulfan on pentobarbitone sleeping time and blood and brain concentrations in male rats. J Pharm Pharmacol 29 245-246. 

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. 

Non-REM parasomnias usually do not require treatment. If needed, low-dose benzodiazepines such as clonazepam can be prescribed for bothersome episodes. Clonazepam reduces the amount of sleep time spent in stages 3 and 4 of non-REM sleep, where most non-REM parasomnias occur. For treating RBD, clonazepam 0.5 to 2 mg at bedtime is the drug of choice, although melatonin 3 to 12 mg at bedtime also may be effective. Patients with RBD also should have dangerous objects removed from the bedroom and cushions placed on the floor to reduce the chance of injury from breakthrough episodes. 

A crude alkaloidal fraction from the stem of Tabernaemontana pandacaqui decreased the motor activity, respiratory rate, induced ataxia, antinociception, and loss of screen grip in rats, suggesting a CNS depression. The extract brought about the prolongation of pentobarbital sleeping time and the oxotremorine-induced salivation, hence possible cholinergic effects (13). 

Dose-dependent effects of transdermal nicotine on early morning awakening and rapid eye movement sleep time in nonsmoking normal volunteers. J. Clin. Psychopharmacol. 14, 264-7. 

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). 

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