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Objective: This the first of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. In this first part of this paper, the general principles of circadian biology that underlie clinical evaluation and treatment are reviewed. We then report on the accumulated evidence regarding the evaluation and treatment of shift work disorder (SWD) and jet lag disorder (JLD).

Objective This the second of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. We herein report on the accumulated evidence regarding the evaluation and treatment of Advamced Sleep Phase Disorder (ASPD), Delayed Sleep Phase Disorder (DSPD), Free-Running Disorder (FRD) and Irregular Sleep-Wake Rhythm ISWR). Methods A set of specific questions relevant to clinical practice were formulated, a systematic literature search was performed, and relevant articles were abstracted and graded. Results A substantial body of literature has accumulated that provides a rational basis the evaluation and treatment of CRSDs. Physiological assessment has involved determination of circadian phase using core body temperature and the timing of melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy and the Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications. Conclusion Circadian rhythm science has also pointed the way to rational interventions for CRSDs and these treatments have been introduced into the practice of sleep medicine with varying degrees of success. More translational research is needed using subjects who meet current diagnostic criteria.

Low oral doses of melatonin raise serum melatonin concentrations to those normally occurring nocturnally and facilitate polysomnographically assessed sleep onset when given at different time points throughout the day, without altering mood or performance on the morning following treatment. In the present study, 12 young healthy volunteers, free of sleep disturbances, received 0.3 or 1.0 mg of melatonin or placebo at 2100 hours, 2-4 hours prior to their habitual bedtime. Polysomnographic recording of overnight sleep began at 2200 hours and continued until 0700 hours the following morning, when subjects were awakened. Sleep onset latency and latency to stage 2 sleep were significantly decreased as a result of melatonin treatment. Neither dose of melatonin significantly altered sleep architecture. Administration of the lower dose of melatonin (0.3 mg) at 2100 hours elevated serum melatonin to levels within the normal nocturnal range (113 +/- 13.5 pg/ml) at the time the sleep test was initiated. Neither melatonin dose caused "hangover effects", as assessed by self-reports or by mood and performance tests administered on the morning following treatment. These observations provide additional evidence that nocturnal melatonin secretion has a sleep-promoting function. They also indicate that an increase in serum melatonin concentrations, within the normal physiologic range, does not significantly alter sleep architecture in subjects with normal sleep who receive the treatment several hours prior to their habitual bedtime.

This the first of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. In this first part of this paper, the general principles of circadian biology that underlie clinical evaluation and treatment are reviewed. We then report on the accumulated evidence regarding the evaluation and treatment of shift work disorder (SWD) and jet lag disorder (JLD).A set of specific questions relevant to clinical practice were formulated, a systematic literature search was performed, and relevant articles were abstracted and graded.A substantial body of literature has accumulated that provides a rational basis the evaluation and treatment of SWD and JLD. Physiological assessment has involved determination of circadian phase using core body temperature and the timing of melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy and the Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications.Circadian rhythm science has also pointed the way to rational interventions for the SWD and JLD, and these treatments have been introduced into the practice of sleep medicine with varying degrees of success. More translational research is needed using subjects who meet current diagnostic criteria.

This review discusses the issue of a dual effect of melatonin on sleep: acute sleep promotion that typically occurs within one hour of administration, and the ability to alter the phase of an underlying circadian pacemaker after a repeated melatonin treatment. The authors suggest that both mechanisms are at work, that they are complementary, and that they may manifest jointly or separately. The review provides some basic information on melatonin, an overview of the literature, and the authors' experience in studying the acute effects of melatonin treatment in humans of different age groups. This review also illustrates the authors' cautious attitude toward melatonin treatment that induces supraphysiologic circulating levels of the hormone.

This review discusses the issue of a dual effect of melatonin on sleep: acute sleep promotion that typically occurs within one hour of administration, and the ability to alter the phase of an underlying circadian pacemaker after a repeated melatonin treatment. The authors suggest that both mechanisms are at work, that they are complementary, and that they may manifest jointly or separately. The review provides some basic information on melatonin, an overview of the literature, and the authors' experience in studying the acute effects of melatonin treatment in humans of different age groups. This review also illustrates the authors' cautious attitude toward melatonin treatment that induces supraphysiologic circulating levels of the hormone.