Sleep dose-response study

Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, Redmond DP, Russo MB, Balkin TJ. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery a sleep-dose response study. J Sleep Res 2003 12 1-12. 

In a sleep dose-response study (3,8) we examined the effects of three conditions of sleep restriction [3, 5, or 7 hr time in bed (TIB)] and one condition of sleep augmentation (9 hr TIB) on performance over 7 days and during the subsequent 3 days of recovery (all groups = 8 hr TIB). These sleep dose-response effects were compared against the training/baseline period in which all groups were allowed 8 hr TIB. 

Belenky, G., Wesensten,N.J., Thome, D.R., Thomas, M.L., Sing, H.C. and Redmond, D.P. et al. (2003), Patterns of Performance Degradation and Restoration during Sleep Restriction and Subsequent Recovery A Sleep Dose-Response Study, Journal of Sleep Research, 12, 1-12. [PubMed 12603781] [DOI 10.1046/J.1365-2869.2003.00337.x]... 

Erman M et al An efficacy, safety, and dose-response study of ramelteon in patients with chronic primary insomnia. Sleep Med 2006 7 17. [PMID 16309958]... 

Mendelson, W.B., Slater, S., Gold, P., and Gillin, J.C. The effect of growth hormone administration on human sleep a dose-response study. Biol Psychiatry 1980, 15 613-618. 

Idzikowski C, Mills FJ, James RJ. A dose-response study examining the effects of ritanserin on human slow wave sleep. Br J Clin Pharmacol 1991 31(2) 193—6. 

Moreover, daily PVT lapse rates increased at a more rapid rate in the reduced sleep conditions. Figure 4 displays the results from the first of these studies, in which subjects were restricted to 4, 6, or 8-hr time in bed for sleep for 14 consecutive days (35). The results were compared to 88 hr of total sleep deprivation. Figure 4 illustrates the dose-response relationship between sleep opportunity and the degree of impairment in PVT performance. Interestingly, this cumulative impairment was found to be almost linear for lapse rates. Further, subjects randomized to the 4- and 6-hr sleep restriction conditions reached levels of impairment equivalent to those of subjects undergoing 1-2 nights of total sleep deprivation. 

Walter Reed-Wistar and Charles River male adult rats were exposed to oral doses of turpentine or to turpentine vapors, which consisted of a- and p-pinene. These exposures were followed by oral administration of heptachlor epoxide or of one of three pesticides, paraoxon, heptachlor, or parathion, or by an intraperitoneal injection of hexobarbital. The studies revealed that pretreatment with turpentine reduced hexobarbital sleeping time, reduced the parathion LDso, and increased the heptachlor LDso. The paraoxon and heptachlor epoxide LOo values were unchanged. a-Pinene and P-pinene vaporized from turpentine had no effect on either hexobarbital sleeping time or parathion, paraoxon, or heptachlor epoxide mortality but did increase the heptachlor LDso (Sperling et al. 1972). The authors speculated that increases in hepatic microsomal enzyme activity are responsible for these differences. 

There have been three randomized clinical trials and multiple case reports and open-label trials with the tricyclic antidepressants (TCAs) in PTSD, although only one study of childhood PTSD (Southwick et al., 1994) has been reported. Robert et al. (1999) reported the use of low-dose imipramine (1 mg/kg) to treat symptoms of ASD in children with burn injuries. In this study, 25 children ages 2 to 19 years were randomized to receive either chloral hydrate or imipramine for 7 days. Ten of 12 subjects receiving imipramine experienced from half to full remission of ASD symptoms, whereas 5 of 13 subjects responded to chloral hydrate. Sleep-related flashbacks and insomnia appeared to be particularly responsive to treatment. 

EXTENSIONS AND COMMENTARY This is a difficult drug to try to determine the active level. It is late. You want to sleep. You take a tab of melatonin and you sleep well. Or you don t take a tab of melatonin and still you sleep well. Or perhaps you sleep badly - what connection can be drawn from the melatonin usage The end-point of these studies is not the enhancement of consciousness but the loss of consciousness. I truly cannot say what the active level might be, because I do not know what positive experience might be expressed with an active level. In my notes is a report of a person who took 80 milligrams, orally. "Apparently I drifted quite quickly and smoothly into sleep, which was sound and which felt natural. On awakening, both my mood and performance seemed enhanced over my usual state." Is that a positive response Melatonin has been espoused as a cure for jet-lag. But when I try to record the doses and... 

The usual starting dose for the treatment of ADHD in children over 5 years of age is 37.5 mg/ day, increased gradually by 18.75 mg/week until the desired response is reached. The usual therapeutic dose range is from 56.25 to 75 mg/day, with a maximum dose of 112 mg/day (57). Since pemoline is not approved for the treatment of narcolepsy, dosage recommendations for this indication are not readily available however, in the subsequent section, dosage information can be extrapolated from a small number of sleep deprivation studies. 

These studies evaluated the safety and efficacy of five dose strengths, three BID regimens and one QD regimen (including BID and QD for one dose level). Individual recorded 24-hour scores for baseline and for 14 day post-baseline determinations. For BID doses, 24-hour scores were calculated as an average of two 12-hour score responses between PM doses. The clinical efficacy measure was symptom score 0 (absent, symptom not present), 1 (mild, symptom was present but not annoying/troublesome), 2 (moderate, symptom was frequently troublesome but did not interfere with either normal daily activity or sleep), 3 (severe, symptom was sufficiently troublesome to interfere with normal daily activity or sleep), 4 (very severe, symptom was so severe as to warrant an immediate visit to physician). Scores were calculated for four such measures and combined with score ranging... 

The role of the a -AR in sedation was revealed in rotarod latency studies, an experimental paradigm that measures the ability of mice to remain on a rotating bar over time impaired motor skills caused by sedation would be predicted to decrease rotarod latency and thus can be interpreted as a measure of the sedative response when unperturbed locomotor response has been documented independently in non-sedated animals. Dexmedetomidine dose-dependently reduced the ability of wild-type mice to remain on the rotarod, whereas a2A-ARl)79N/D79N and ot2A-AR /- mice were resistant to even supramaximal doses (5,29). Consistent with these observations, ot -AR mice did not sleep, as assessed via loss-of-righting reflex (5). These findings indicate that the cx -AR subtype is required to mediate the sedative effects of a2-AR agonists (Table 1). 

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