s Editorial [ Hot Topic: Therapeutic Opportunities in the Treatment of Sleep Disorders (Guest Editor: Margaret Bradbury) ]

Sleep disorders, including chronic insomnia, continue to be considerably under-treated medical conditions. A recent poll conducted by the National Sleep Foundation [1] estimated that a quarter of the respondents considered their sleep poor to fair. When quizzed by symptoms, even more individuals qualified for an insomnia diagnosis. As recently as 2005, a National Institutes of Health State of the Science Conference was convened to discuss the manifestation and management of chronic insomnia [2]. The panel concluded that insomnia ranks highly among the critical public health issues facing the U.S. In addition, the panel recognized a bi-directional relationship between mood disorders and sleep disorders, highlighting that insomnia is a prevalent risk factor for depression. Several studies also identify insomnia as a significant risk factor for absenteeism, impaired job performance and accidents [3, 4]. The burden of insomnia on society is significant; recent estimates suggested direct costs of approximately US$13.9 billion in 1995, with indirect costs less well-defined, but also substantial [5, 6]. Despite the prevalence of sleep disorders, a majority of those with sleep disorders do not receive outside support whether through behavioral modifications or medication [4]. The mainstay in insomnia treatment has been benzodiazepines and newer modulators of the GABA-A receptor. While there continue to be efforts in this area, new drug discovery efforts for sleep disorders is spreading into new pharmacological arenas with growing understanding of basic mechanisms of sleep regulation. This special issue of CNS and Neurological Disorders- Drug Targets will provide an overview of current and future approaches to treating insomnia and other sleep disorders. Although not an exhaustive list of all potential new targets, these chapters bring important insights into some of the most exciting areas for new therapies for sleep disorders. In the first chapter, Gary Zammit, a leader in clinical trials for new sleep medications, reviews the prevalence and current treatments for insomnia ranging from behavior therapy to over-the-counter medications, to current on and off-label prescription options. He also provides additional discussions of potential upcoming treatments in the areas of GABA modulation and melatonin receptor activation, and provides insight into future directions for research and clinical trial development. Nicholas DeMartinis and Andrew Winokur, experts in the interactions between mood disorders and sleep, review the impact of psychiatric medicines on disordered sleep, assessing their role in both primary insomnia and in other sleep disorder syndromes. They also discuss current efforts by the pharmaceutical industry to reposition psychiatric medications for labeled use in sleep disorders. While antihistamine-containing products are widely available and used frequently for acute insomnia treatment [7], the evidence supporting their beneficial effect is not consistent. In the third chapter, Ann Barbier and Margaret Bradbury examine the neurobiological rationale for the use of antihistamines in over-the-counter treatment of insomnia. The current antihistamines most likely produce their sedative effects via antagonism of the H1 receptor. However, recent preclinical and clinical data suggest that histamine H3 receptors may also be promising targets for the treatment of wake and sleep disorders. Many neuropeptides have been recently identified, and some have been found to significantly modulate sleep. In recent years, Seiji Nishino and colleagues have been instrumental in revealing the link between disruptions in the orexin / hypocretin system and narcolepsy with cataplexy. The authors provide an extensive review of the orexin system, and also review the effects of various neuropeptides in normal and pathophysiological sleep states. The last two chapters move away from GABA-A receptor modulators and G-protein coupled receptors to more novel areas. Modulation of ion channels remains a relatively poorly explored area in sleep research, despite the fact that electrical activity is at the very core of sleep and its measurement through the electroencephalogram (EEG).....