Safety and subjective sleep effects of ramelteon administration in adults and older adults with chronic primary insomnia: a 1-year, open-label study.

Objective: To evaluate the long-term safety and subjective sleep effects of ramelteon in adults with chronic insomnia.

Method: Subjects with primary insomnia (DSM-IV-TR criteria) for >or= 3 months received ramelteon nightly for 1 year; a 3-day placebo run out followed. Subjects aged >or=65 years received open-label ramelteon 8 mg (N = 248); those aged 18 to 64 years received ramelteon 16 mg (N = 965).

Circadian phase-shifting effects of repeated ramelteon administration in healthy adults.

Study Objectives: To assess the ability of repeated daily oral ramelteon to facilitate re-entrainment of human circadian rhythms after an imposed phase advance of the sleep-wake cycle.

Methods: A total of 75 healthy adult volunteers aged 18-45 years remained in a sleep laboratory for 6 days and 5 nights; a 5-h phase advance in their sleep-wake cycle was imposed under dim-light conditions. Oral ramelteon (1,2, 4, or 8 mg once daily for 4 days) or placebo was administered 30 min before bedtime.

Human physiological models of insomnia.

Despite the wide prevalence and important consequences of insomnia, remarkably little is known about its pathophysiology. Available models exist primarily in the psychological domain and derive from the demonstrated efficacy of behavioral treatment approaches to insomnia management. However, these models offer little specific prediction about the anatomic or physiological foundation of chronic primary insomnia.

Circadian rhythmicity and the pharmacologic management of insomnia.

The circadian clock modulates timing of sleep and wakefulness. In certain situations, the circadian potentiation of wakefulness may interfere with desired sleep-scheduling, particularly in the elderly and shift workers. Known abnormalities of circadian regulation are defined by their impact on sleep-wake state expression.

The human circadian system in normal and disordered sleep.

The human circadian system regulates rhythmicity in the human body and establishes normal sleep and wake phases. The suprachiasmatic nuclei (SCN), located in the hypothalamus above the optic chiasm, make up the human pacemaker known as the circadian or biological clock, but other essential parts of the circadian system include the pineal gland, retina, and retinohypothalamic tract. The importance of light in resetting the intrinsic human circadian cycle, the intrinsic period of which is slightly longer than 24 hours, ensures that the human cycle will stay entrained to the earth's 24-hour daily cycle.

Long-term use of sedative hypnotics in older patients with insomnia.

Background And Purpose: Insomnia is a common problem that increases with age and can last months to years. While substantial data establish the efficacy and safety of short-acting hypnotic therapy for the management of short-term insomnia using benzodiazepines receptor agonists (BzRAs), there are few studies on the continued efficacy and safety of these drugs when used for sustained periods. This paper reports the results of a 1-year open-label extension phases of two randomized, double-blind trials of zaleplon.

Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase.

To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP.

Epidemiology of insomnia and the need for diagnosis and treatment.

Insomnia is a common complaint of patients, yet not all patients have primary insomnia. Insomnia can be a significant health problem and may also accompany aging, stress, depression, and other illnesses. Several barriers exist to treatment, but incorporating simple questions may serve as step in guiding diagnosis and treatment.

Tolerance to daytime sedative effects of H1 antihistamines.

Sedation is the principal side effect of first generation H1 antihistamines, and recent studies have suggested that this side effect should limit the clinical application of these drugs. The sedative effect also underlies the use of these first-generation drugs as nonprescriptive remedies for insomnia. In both cases, the potential for tolerance to the sedative effect of these drugs is an important issue for which there are few objective data.

Management of insomnia--the role of zaleplon.

Context: Insomnia is the most frequently reported sleep symptom, severely affecting up to 15% of the US population. The need to effectively treat this disorder is underscored by the significant adverse consequences on the productivity, safety, overall health, and quality of life of the affected individual. Pharmacologic intervention has traditionally involved the use of benzodiazepine receptor agonists (BzRAs), for which efficacy and general safety have been established.