Ramelteon for the treatment of insomnia in menopausal women.

Sleep disturbances have been reported to be one of the most troubling manifestations of menopause, affecting 45−75 % of women.1,2 Menopausal women report a significantly higher rate of sleep difficulties compared to pre-menopausal women, including problems with onset, maintenance, and frequent hypnotic use.3 Although sleep problems may be related to other menopausal complaints such as hot flashes or night sweats, menopausal insomnia can also occur in the absence of these vasomotor symptoms.1,2 Because menopausal insomnia is linked with high rates of mental health concerns, functional impairment, and poor quality of life,4,5 the effective treatment of sleep disturbances in this population of women is important. Since many of the physiological changes that occur during menopause result from decreased levels of estrogen, hormone replacement therapy (HRT) has historically been considered a first-line treatment for menopausal insomnia.6 HRT has been found to decrease latency to sleep onset, nocturnal waking, and total sleep time in menopausal women.3 However, HRT is associated with numerous risks and side effects which often result in a failure to initiate, poor adherence to, or an abrupt discontinuation of treatment regimens.7,8,9 Due to these concerns about the HRT side-effect profile, many women are increasingly seeking alternative treatments.10 For example, 79% (n=395) of the peri and postmenopausal women surveyed at a large community clinic reported using botanical dietary supplements, that they believed to be safe, to address their current health concerns.11 Melatonin is the main hormone secreted by the pineal gland and is involved in the regulation of the sleep-wake cycle. A steep, age-related decline in melatonin has been documented in women up to 15 years postmenopausal with a gradual decline noted thereafter.12 It has been proposed that individuals with reduced melatonin levels may benefit from melatonin supplementation.13 In fact, a recent meta-analysis suggests that exogenous melatonin treatment decreases sleep onset latency and increases both sleep efficiency (e.g., decreased number of awakenings during sleep, shortened periods of wakefulness) and total sleep duration.14 These improvements in sleep have been linked to improved attention, concentration, fine motor skills, reaction time, daytime alertness, and overall quality of life.15,16 Moreover, the administration of exogenous melatonin has specifically been associated with improved sleep quality and good tolerability in perimenopausal women.17 Thus, ramelteon, a selective melatonin receptor agonist, may be an effective and more readily accepted alternative treatment option for menopausal insomnia. Compared to melatonin, ramelteon is structurally different and is up to 17 times more potent at specific melatonin receptors.18 In addition, ramelteon has scientific evidence of efficacy and safety at the recommended doses, 19,20 and is subject to the good manufacture practices enforced by the United States Food and Drug Administration (FDA).i This report details the first study to investigate the use of ramelteon (8mg) for the treatment of insomnia in menopausal women. It was hypothesized that ramelteon will result in significant improvement in patient-reported latency to sleep onset (primary hypothesis), as well as significant improvements in patient-rated total sleep time, wake time after sleep onset, number of awakenings, sleep quality, severity of insomnia, quality of life, depressive and anxious symptoms, and daytime functioning (secondary hypotheses) in this 6-week open-label trial.