2. Efficacy and Safety of Valerian Extracts 
The clinical relevance of acute as well as chronic sleep disorders is obvious: epidemiological data show that they affect approximately one-third of the adult population [6, 7]. Treatment is indicated in about 15% of these cases [8, 9]. Insomnia, defined as insufficient quantity or quality of sleep resulting in compromised daytime alertness and activity, is a common condition. It can result in serious adverse consequences, including attention and memory impairment, depression, falls, and perceived reduced quality of life [10].
To the most common treatments of insomnia belong drugs [11], this however bears some problems. Benzodiazepines and imidazopyridines offer only short-term relief, while data on their long-term efficacy are scarce. Both drug classes have significant adverse effects such as serious psychomotor symptoms, behavioral aberrations, memory impairment resulting in injuries, respiratory depression, rebound insomnia, and paradoxical agitation. Especially for benzodiazepines, the potential for abuse is high [10]. Therefore, the National Institutes of Health consensus conference strongly discouraged chronic treatment of insomnia with benzodiazepines already in 2005 [11].
Sedating antihistamines, such as diphenhydramine, the active ingredient in most over-the-counter sleep aids, are associated with cognitive impairment, daytime drowsiness, and anticholinergic effects. There is no evidence-based data available on their efficacy improving insomnia or prolonging sleep. It therefore was recommended that they should be avoided in the elderly [10, 12]. Finally, antidepressants used for treating insomnia, such as trazodone, can produce dangerous and life-threatening adverse events due to their anticholinergic, cardiovascular, and neurologic actions [10, 12].
Herbal substances improving insomnia, such as valerian, hops, or passion flower, are well-known sleep aids. While marketed as food in the US, they are authorized or registered as medicines in Europe and many other regions, being mostly used in self-medication and holding widespread appeal, presumably because of their lower cost and higher range of safety when compared to chemically defined pharmaceuticals [13]. Among these, the roots of valerian (Valeriana officinalis L.) are the most familiar ones, especially in Europe. They improve the subjective experience of sleep when taken in the evening over a period of one or two weeks [14]. The constituents of valerian root include, among others, valepotriates (iridoids) and volatile oil, including monoterpenes and sesquiterpenes (valerenic acids). Commercially available extracts are free from valepotriates [15]. Recommended daily doses of valerian root extracts are about 600 mg, usually taken as capsules or tablets.
Several controlled clinical trials with various valerian extracts are available, and also a meta-analysis on eighteen randomized placebo-controlled trails was published. Its qualitative results suggest that valerian would be effective for a subjective improvement of insomnia, although its effectiveness could not be demonstrated with quantitative or objective measurements [16]. In a study conducted in cancer patients, an improvement in the primary variable, a sleep quality index based mainly on objective parameters, could not be demonstrated; however, fatigue and sleep problems were significantly improved [17].
The clinical studies available show an excellent short-term tolerability, and from several decades of clinical use within the frame of pharmacovigilance systems no data questioning its long-term safety have evolved, while prospective data are missing [18]. In contrast to classical sedatives, valerian extracts did not impair the ability to drive or to use machines, neither after single [19–22] nor after repeated doses [23]. Reports of putative adverse reactions are extremely rare and include one case of hepatic symptoms after prolonged treatment and one case of cardiac symptoms after discontinuation of a long-term treatment with very high doses, which were interpreted as a withdrawal reaction [24, 25]. In both case reports, outcome was benign, causality was questionable, and characteristics of the extract preparations were not provided.
While the side effect profile therefore is benign, a potential for adverse drug interactions has been claimed by some reviews [26], while other reviews did not [18, 27–32], so that a reevaluation of the existing evidence is necessary.