Sleep maintenance

Insomnia complaints are common in the general population and can be dichotomized into problems of delayed sleep onset and those related to sleep maintenance. Increasing attention is being focused on the adverse daytime effects of insomnia. Sleep disturbances become more common with increased age and are more prevalent in women. Sleep complaints arise from very diverse etiologies which prominently include concomitant primary... 

Lancel, M. and Langebartels, A. (2000) gamma-aminobutyric Acid(A) (GABA(A)) agonist 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol persistently increases sleep maintenance and intensity during chronic administration to rats../. Pharmacol. Exp. Ther. 293,1084-1090. 

Eplivanserin (39) is a 5-HT2A antagonist initially developed for a broader spectrum of psychiatric disorders but that has been tested recently for insomnia. Within this latter indication, phase II studies showed benefits in sleep maintenance, but not in induction [9]. Compound 39 is currently in phase III, to assess the efficacy for the treatment of sleep maintenance insomnia, evaluating both sleep and daytime functioning [96]. 

Pimavanserin tartrate (40, ACP-103) is a 5-HT2A receptor inverse agonist currently in phase II clinical development as an antipsychotic agent and for insomnia, focused on sleep maintenance, evaluating slow-wave-sleep at doses of 5 and 20 mg [97,98]. 

Extended-release For the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). 

Adults The recommended starting dose for eszopiclone is 2 mg immediately before bedtime. Dosing can be initiated at or raised to 3 mg if clinically indicated for sleep maintenance. 

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. 

Walsh, J.K., Poliak, C.P., Scharf, M.B., Schweitzer, P.K., and Vogel, G.W. (2000) Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia. Clin Neuropharmacol 23 17—21. 

The TCAs appear to reduce symptoms of reexperiencing and depression related to PTSD. In children and adolescents, imipramine may be an effective agent for ASD symptoms, especially traumatic experiences or flashbacks related to sleep onset and sleep maintenance (Robert et al., 1999). Because of their safety and side effect profile and the apparent lack of effectiveness in childhood depression, the TCAs have been supplanted by the SSRIs as first-line pharmacotherapy in the treatment of depression and anxiety in childhood. As such, these agents should be reserved for second- or third-line treatment in pediatric PTSD. 

Trials of different modified-release formulations of zaleplon, zolpidem, and a similar selective GABA hypnotic, indiplon, are ongoing. These versions may help improve the sleep of those patients who have sleep maintenance insomnia or early-morning awakening. 

Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia assessment in a clinical trial of melatonin replacement. Sleep 1998 21 52-68. 

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. 

Edinger JD, Hoelscher TJ, Marsh GR, Lipper S, Ionescu-Pioggia M. A cognitive-behavioral therapy for sleep-maintenance insomnia in older adults. Psychol Aging 1992 7 282-289. 

Hoelscher TJ, Edinger JD. Treatment of sleep-maintenance insomnia in older adults Sleep period reduction, sleep education, and modified stimulus control. Psychol Aging 1988 3 258-263. 

Stage 2 sleep latency Sleep maintenance Decrease Decrease Decrease Decrease Decrease... 

Cinolazepam was evaluated in a doubleblind placebo controlled trial in 20 normal subjects. The subjects were given either placebo or 40 mg cinolazepam orally 30 min before bedtime. A significant improvement in sleep maintenance was obtained with 40 mg cinolazepam, measured by sleep disruption using nocturnal traffic noise. Sleep architecture was only minimally affected, and sleep quality improved significantly (65). 

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