Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. Data sources 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003). Study selection The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials. Quality assessment Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist. Data extraction and synthesis One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data. Main results Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference − 13.2 (95% confidence interval − 27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction ( − 1.0 ( − 2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less). Conclusions There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.

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BACKGROUND:Hypnotics have a role in the management of acute insomnia; however, the efficacy and safety of pharmacological interventions in the management of chronic insomnia is unclear. OBJECTIVE:The objective of this paper is to conduct a systematic review of the efficacy and safety of drug treatments for chronic insomnia in adults.DATA SOURCES: Twenty-one electronic databases were searched, up to July 2006.STUDY SELECTION: Randomized double-blind, placebocontrolled trials were eligible. Quality was assessed using the Jadad scale. Data were pooled using the random effects model. DATA SYNTHESIS:One hundred and five studies were included in the review. Sleep onset latency, as measured by polysomnography, was significantly decreased for benzodiazepines (BDZ), (weighted mean difference: −10.0 minutes; 95% CI: −16.6, −3.4), non-benzodiazepines (non-BDZ) (−12.8 minutes; 95% CI: −16.9, −8.8) and antidepressants (ADP) (−7.0 minutes; 95% CI: −10.7, −3.3). Sleep onset latency assessed by sleep diaries was also improved (BDZ: −19.6 minutes; 95% CI: −23.9, −15.3; non-BDZ: −17.0 minutes; 95% CI: −20.0, −14.0; ADP: −12.2 minutes; 95% CI: −22.3, −2.2). Indirect comparisons between drug categories suggest BDZ and non-BDZ have a similar effect. All drug groups had a statistically significant higher risk of harm compared to placebo (BDZ: risk difference [RD]: 0.15; non-BDZ RD: 0.07; and ADP RD: 0.09), although the most commonly reported adverse events were minor. Indirect comparisons suggest that non-BDZ are safer than BDZ.CONCLUSIONS: Benzodiazepines and non-benzodiazepines are effective treatments in the management of chronic insomnia, although they pose a risk of harm. There is also some evidence that antidepressants are effective and that they pose a risk of harm.

Background: Exogenous melatonin has been increasingly used in the management of sleep disorders. Purpose: To conduct a systematic review of the efficacy and safety of exogenous melatonin in the management of primary sleep disorders. Data Sources: A number of electronic databases were searched. We reviewed the bibliographies of included studies and relevant reviews and conducted hand‐searching. Study Selection: Randomized controlled trials (RCTs) were eligible for the efficacy review, and controlled trials were eligible for the safety review. Data Extraction: One reviewer extracted data, while the other verified data extracted. The Random Effects Model was used to analyze data. Data Synthesis: Melatonin decreased sleep onset latency (weighted mean difference [WMD]: −11.7 minutes; 95% confidence interval [CI]: −18.2, −5.2)); it was decreased to a greater extent in people with delayed sleep phase syndrome (WMD: −38.8 minutes; 95% CI: −50.3, −27.3; n=2) compared with people with insomnia (WMD: −7.2 minutes; 95% CI: −12.0, −2.4; n=12). The former result appears to be clinically important. There was no evidence of adverse effects of melatonin. Conclusions: There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short‐term use (4 weeks or less); however, additional large‐scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short‐term use. There is evidence to suggest that melatonin is safe with short‐term use (3 months or less).

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Most clinical trials on meditation practices are generally characterized by poor methodological quality with significant threats to validity in every major quality domain assessed. Despite a statistically significant improvement in the methodological quality over time, it is imperative that future trials on meditation be rigorous in design, execution, analysis, and the reporting of results.

Abstract-Phosphorylation of myofilament proteins by kinases such as cAMP-dependent protein kinase and protein kinase C has been shown to lead to altered thin-filament protein-protein interactions and modulation of cardiac function in vitro. In the present study, we report that a small GTPase-dependent kinase, p21-activated kinase (PAK), increases the calcium sensitivity of Triton-skinned cardiac muscle fiber bundles.

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