Clinical Management of Insomnia

Insomnia is the most common sleep disorder, with a prevalence of around 20%. The clearest risk factors are female gender and the presence of a psychiatric or medical disorder. The most important conceptual change in our understanding of insomnia, defined in the National Institutes of Health 2005 consensus conference, is that insomnia is a disorder itself rather than a symptom of another disorder. Specifically, insomnia is a disorder of hyperarousal. Insomniacs do not have an abnormal sleep homeostat or circadian system but rather an overactivated wake system. Cognitively, patients often complain they cannot “shut [their] brain down.” Physiologic correlates include elevated brain metabolism, increased fast electroencephalographic activity, and increased autonomic, metabolic, and hypothalamic-pituitary-adrenal axis activity. Treatment for insomnia can be divided into two categories, behavioral and pharmacologic. Another important categorization relates to self-treatment (sleep hygiene and over-the-counter drugs) versus clinician-directed therapy (cognitive-behavioral therapy for insomnia [CBT-I] and prescribed hypnotics). Among behavioral treatments are sleep restriction, stimulus control, relaxation training, and cognitive therapy. The most widely used behavioral therapy is a combination of the four treatment components referred to collectively as CBT-I. The majority of Food and Drug Administration (FDA)-approved hypnotics are drugs that occupy the benzodiazepine receptor site, which is part of the GABAA receptor complex. The hypnotic efficacy of the FDA-approved benzodiazepine receptor agonists (BzRAs) has been well documented using objective polysomnography and subjective measures of sleep induction and duration. Many BzRA side effects are associated with the desired sedative effects of the drug and relate to the pharmacokinetics, receptor subtype affinities, and dose of the drug. Key words: behavioral therapy, GABA, histamine, insomnia disorder, melatonin, orexin, pathophysiology, pharmacotherapy

The Use of Valerian in Neuropsychiatry

ABSTRACTValerian is a medicinal agent deriving from the plant Valeriana officinalis L. We reviewed the available literature on the use of valerian preparations in the treatment of neuropsychiatric disorders. Preclinical studies suggest that valerian has sedative and muscle-relaxant effects. Few clinical trials with valerian have been carried out in conditions other than insomnia. The insomnia studies have methodologic shortcomings but suggest that some preparations lead to significant subjective improvement in sleep complaints with remarkably few side effects. Furthermore, some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. If this safety profile and the plant's sedative/hypnotic efficacy are confirmed in double-blind, placebo-controlled trials with carefully and consistently prepared valerian compounds, then those compounds would fill an important and presently unfilled niche in the treatment of insomnia.

Efficacy of zolpidem in insomnia

SummaryThe efficacy of zolpidem, a non benzodiazepine hypnotic agent with a short elimination half life, was reviewed, analysing more than 50 international clinical trials published since 1986. The hypnotic activity of zolpidem has been explored in different patient populations including normal volunteers, general practice outpatients and psychiatric out- or in-patients with varying sleep disorders; both transient and chronic. Assessment methods used have included objective and subjective measures of hypnotic efficacy for different treatment durations, with results confirming that 10 mg is superior to placebo. Zolpidem was shown to be superior in most trials on sleep parameters such as total sleep time, sleep onset latency and nocturnal awakenings, but total REM sleep and REM latency were usually unmodified. Zolpidem maintained normal sleep physiology as demonstrated by the preservation of slow wave stages and no, or minimal, effects on sleep architecture after abrupt discontinuation. Consequently, 10 mg is the recommended dose for the short-term treatment of insomnia in the non-elderly; in elderly patients 5 mg has been shown to be effective at inducing sleep whilst giving an optimum safety profile.