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Abstract
To show better improvement of sleep quality when treating non-organic insomniacs with extractum Valerianae radix siccum instead of oxazepam.
Randomised, double blind, comparative study.
Out-patients of 8 general practitioners.
Non-organic and non-psychiatric insomniacs aged between 18 and 70 years were included into the trial. Persons with known hypersensitivity to valerian or benzodiazepines, other psychotropic drugs and various contraindications/limitations for benzodiazepines were excluded.
75 patients were randomly allocated either to the index group (2 x 300 mg extractum Valerianae radix siccum dragées LI 156) or control group (2 x 5 mg oxazepam dragées). The patients took study medication daily over a period of 28 days 30 min before going to bed.
The factor sleep quality of the SF-B was defined as primary outcome. Secondary outcomes were other sleep characteristics of the SF-B, well-being (Bf-S) and anxiety (HAMA). Controls were performed before treatment as well as after 1, 2 and 4 weeks. Vital and laboratory parameters as well as unexpected events were assessed for safety and tolerability.
For all outcomes effect sizes between groups were calculated. For the main outcome criteria significance was tested by repeated-measures ANOVA considering all cases for which data of at least one follow-up existed (n = 70).
Baseline characteristics were well balanced. 70% (54/75) of the patients were females, over 53% (40/75) reported insomnia for more than 1 year. Mean age was 52 +/- 12 years. In both groups sleep quality improved significantly (p <0.001), but no statistically significant difference could be found between groups (p = 0.70). Effect sizes between groups varied between 0.02 and 0.25. Five persons withdrew due to possibly adverse drug reactions (2 ( valerian, 3 ( oxazepam). No serious adverse events happened.
The study showed no differences in the efficacy for valerian and oxazepam. Because of the more favourable adverse effect profile of valerian compared to oxazepam, this hypothesis should be analysed confirmatorily in an equivalence study.
... In two double-blind and placebo-controlled studies, single doses between 400 and 900 mg significantly improved sleep latency and sleep quality when compared with placebo
[34,35]. In two randomized, double-blind studies, the effects of Valeriana (600 mg/d) on insomnia were comparable to those of Oxazepam
[36,37]. Interestingly, a high dosage of Valeriana (1500 mg Valeriana in combination with 360 mg hops) particularly increased δ-waves in human subjects
[38]. ...
... In two double-blind and placebocontrolled studies, single doses between 400 and 900 mg significantly improved sleep latency and sleep quality when compared with placebo [34,35] . In two randomized , double-blind studies, the effects of Valeriana (600 mg/d) on insomnia were comparable to those of Oxazepam [36,37]. Interestingly, a high dosage of Valeriana (1500 mg Valeriana in combination with 360 mg hops) particularly increased δ-waves in human subjects [38]. ...
Background
Various medications of natural origin have effectively treated stress-related disorders, such as sleep disturbances and agitated conditions. The efficacy of Neurexan, a multicomponent, low-dose medication, has been demonstrated in observational studies, but its exact mechanism of action has not been determined.
Methods
To characterize the effects of Neurexan on the central nervous system, we analyzed the spectral frequencies of field potentials in four rat brain areas after a single oral administration of Neurexan. Different doses of Neurexan were tested within a crossover design, and effects were compared with vehicle control.
Results
Significant effects were observed with 0.5 tablets of Neurexan, predominantly on δ- and θ-waves in the frontal cortex and reticular formation (P < 0.01). In the reticular formation, significant changes of δ- and θ-waves occurred as early as during the first hour after administration. The time course revealed a significant and longer-lasting increase of δ- and θ-waves in the frontal cortex and reticular formation, whereas other spectral frequencies were only transiently affected in the frontal cortex, reticular formation, and striatum.
Conclusion
In conclusion, this study demonstrated that the low-dose medication Neurexan influences central nervous system activity in rats. The resulting electroencephalographic profile of Neurexan shows several similarities with those of other calming agents, such as Valeriana and Passiflora, suggesting a potential benefit of Neurexan for patients with stress-related disorders. Moreover, this report demonstrates that electroencephalographic signatures are also valid biomarkers for the assessment of low-dose medications, such as Neurexan.
... Using subacute treatment regimes, an extract made with 70% v/v ethanol affected different sleep parameters in a positive manner as well (Donath et al., 2000;Vorbach et al., 1996). Furthermore an improvement of sleep quality comparable to treatment with 10 mg oxazepam was observed for the same ethanolic extract in two comparative studies (Dorn, 2000;Ziegler et al., 2002). ...
... Additionally, several observations indicate a putative efficacy of valerian preparations in the treatment of anxiety and stress-related symptoms. In a comparative study a 4 week treatment with a 70% v/v ethanolic extract led, amongst others, to a reduction of the Hamilton-scores similar to the oxazepam treated group (Dorn, 2000). Furthermore, after a treatment period of 1 week using the same extract a diminished response to mental stress under laboratory conditions was reported by Cropley et al. (2002). ...
Extracts of Valeriana officinalis L. s.l. are used for treating mild sleep disorders and nervous tension. Despite intensive research efforts, the pharmacological actions accounting for the clinical efficacy of valerian remain unclear. Thus, it was the aim of this study to evaluate CNS-related effects of different valerian extracts using behavioral paradigms (mice and rats). Following oral administration two commercially available preparations (extraction solvents: 45% methanol m/m and 70% ethanol v/v), a 35% ethanolic v/v extract and a refined extract derived from it (patented special extract phytofin Valerian 368) were tested for sedative (locomotor activity, ether-induced anaesthesia) and anxiolytic (elevated plus maze) activity. Using the forced swimming and the horizontal wire test the latter two extracts were additionally tested for antidepressant and myorelaxant properties. Up to maximum dosages of 500 or 1000 mg/kg bw none of the valerian extracts displayed sedative effects. Neither spontaneous activity was reduced nor the duration of ether-induced narcosis was prolonged. In contrast, results obtained in the elevated plus maze test revealed a pronounced anxiolytic effect of the 45% methanolic and 35% ethanolic extract as well as of phyotofin Valerian 368 in a dose range of 100-500 mg/kg bw. Additionally and different from its primary extract (35% ethanolic extract) phytofin Valerian 368 showed antidepressant activity in the forced swimming test after subacute treatment. Myorelaxant effects were not observed in dosages up to 1000 mg/kg bw. Due to these findings it is proposed that not sedative but anxiolytic and antidepressant activity, which was elaborated particularly in the special extract phytofin Valerian 368, considerably contribute to the sleep-enhancing properties of valerian.
... Key ingredients include melatonin, L-tryptophan, gamma-aminobutyric acid (GABA) and several herbal extracts (e.g., Sensoril®, Ashwagandha, Valerest TM , a blend of hops and valerian and Chamomile Passionflower). Many herbs like Valerest TM and Chamomile Passionflower have a long history of use as mild sedatives and hypnotics which may contribute to sleep improvement [3][4][5][6][7][8]. Extensive studies have been conducted on immediate release and sustained release melatonin products [9]. ...
... The studies showed that V. officinalis root improved sleep quality [168], reduced sleep latency and improved the subjective sleep rating [169], decreased insomnia symptoms [170] and also improved sleep quality with results comparable to those obtained by the administration of 10 mg of oxazepam but with fewer side effects [171]. Conversely, subsequent randomized double-blind studies based on sleep parameters evaluated objectively with polysomnographic techniques detected no substantial differences on any of the measurements in comparison to the placebo group except for only one parameter [172]. ...
Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispas-modic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valeriana officinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed,
... Dies bestätigt eine Meta-Analyse randomisierter, placebokontrollierter Studien, die eine subjektive Verbesserung der Insomnie feststellte [47]. Baldrian verbesserte den Schlaf und Angstsymptome vergleichbar wirksam wie Oxazepam [48,49]. Aufgrund seiner milden sedierenden Effekte und schlaffördernden Wirkung stellt Baldrian eine verträgliche Alternative und einen möglichen Ersatz für synthetische Sedativa dar [31]. ...
... IVA is also a component of valerian root, an herbal medicine used since ancient Greek and Roman times to treat insomnia, and since medieval times in Europe specifically to treat seizures 34,35 . Valerian root extract is still used extensively today for anxiety and insomnia, although randomized controlled trials evaluating its efficacy have achieved mixed results [43][44][45] . It has been estimated that 10 g of valerian root might yield as much as 100 mg of IVA, and that valerian root doses of 30-50 g per day would have the potential for anticonvulsant activity 46 . ...
Epilepsy has been treated for centuries with herbal remedies, including leaves of the African shrub Mallotus oppositifolius, yet the underlying molecular mechanisms have remained unclear. Voltage-gated potassium channel isoforms KCNQ2-5, predominantly KCNQ2/3 heteromers, underlie the neuronal M-current, which suppresses neuronal excitability, protecting against seizures. Here, in silico docking, mutagenesis and cellular electrophysiology reveal that two components of M. oppositifolius leaf extract, mallotoxin (MTX) and isovaleric acid (IVA), act synergistically to open neuronal KCNQs, including KCNQ2/3 channels. Correspondingly, MTX and IVA combine to suppress pentylene tetrazole-induced tonic seizures in mice, whereas individually they are ineffective. Co-administering MTX and IVA with the modern, synthetic anticonvulsant retigabine creates a further synergy that voltage independently locks KCNQ2/3 open. Leveraging this synergy, which harnesses ancient and modern medicines to exploit differential KCNQ isoform preferences, presents an approach to developing safe yet effective anticonvulsants.
... This study suggests that valerian's effects may be cumulative, with optimal effects occurring with persistent use over a period of at least one month. @BULLET Dorn et al (2000)-Well-designed double blind trial (n=75) comparing a dry ethanolic valerian extract (Sedonium, 600mg/day) with benzodiazepine oxazepam (10mg/day). The sample included primarily older female patients who had complained of insomnia for over one year. ...
Herbal medicines fact sheets. The four herbal medicines fact sheets developed, implemented, and evaluated in this study.
... Comparison with a Benzodiazepine Dorn 43 reported the result of a double-blind, comparative study, in outpatients from eight general practitioners. Seventyfive patients between 18 and 70 years of age were randomly assigned either to the test group (2 doses of 300 mg valerian extract, LI 156) or the control group (2 doses of 5 mg oxazepam for 28 days, 30 min before bed). ...
The World Health Organization estimates that 80% of the world’s population relies on herbal medicine, with the use of herbs in the United States expanding significantly in the past decade. Alternative and herbal medicines—such as St. John’s wort, kava, ginkgo biloba, and valerian, among others—have become increasingly popular treatments for nervous and sleep disorders including stress, anxiety, dementia, and forgetfulness. This article reviews the use of ginkgo, kava, passionflower, and valerian in psychiatric practice, summarizing existing research on these major botanicals. Herbal remedies are compared with pharmaceuticals, and dosages, benefits, adverse effects, and drug–herb interactions are discussed for each herb.
... There are no substantial long-term studies of safety or benefit. 199,200 • Lemon balm, hops, passion flower and skullcap are other less well-studied herbs that might have value for sleep and that are sometimes combined with Valerian. ...
... 75 Valerian extract LI 156 (600 mg) was as effective as oxazepam 10 mg for improving sleep quality when given 30 minutes before bedtime to 74 patients with insomnia for 28 days. 76 Valerian is generally well-tolerated, although some clinical trials have reported morning sedation. Unlike flunitrazepam (1 mg), a single dose 600 mg of LI 156 did not impair reaction abilities, concentration, and coordination. ...
Safety and efficacy issues surrounding the use of the most popular herbs are discussed. The various herbs classified under the general heading "ginseng" are compared and contrasted. Echinacea is commonly used for treating colds and flu. St. John's Wort is among the best studied herbs in terms of efficacy in treating depression and drug interactions. Saw palmetto is used to treat benign prostatic hypertrophy with a minimum of side effects and drug interactions. Garlic has a wide range of uses, including hyperlipidemia, hypertension, and infections. Kava kava shows promise as an alternative for mild anxiety disorders. Valerian has been used with some success to treat insomnia. Ginkgo has gained acceptance for treating dementia, memory loss, and intermittent claudication. Goldenseal is a popular but probably ineffective antiseptic and agent for masking drug screens. Milk thistle may have a role in treating liver disease of various origins. Aloe is used as a laxative and to treat wounds. Black cohosh is a popular herb for treating the symptoms of menopause.
... Using subacute treatment regimes, an extract made with 70% v/v ethanol affected different sleep parameters in a positive manner as well [39]. Furthermore an improvement of sleep quality comparable to treatment with 10 mg oxazepam was observed for the same ethanolic extract in two comparative studies [40,41]. Another in vivo experiment revealed a significant shortening of sleep latency in sleep-disturbed rats after treatment with a 70% ethanolic preparation [42]. ...
The genus Valeriana (Valerianaceae) contains over 250 species distributed
around the world and used in traditional medicines of many cultures. The main compounds
isolated from Valeriana species are essential oils, valerenic acid and its derivatives and
iridoids, accumulated mainly in the roots and rhizomes. This review lists 135 chemical
constituents as well as their biosynthesis and bioactivity as reported by the end of 2008 (80
references).
... In two studies on small numbers of subjects, insomniacs rated valerian and oxazepam as being equally effective. 57,58 In another trial, valerian was used to control insomnia that arose after benzodiazepine withdrawl. 59 It is hard to ascertain the incidence of side effects of valerian from observations with such a limited number of subjects. ...
Insomnia is a frequent problem among the elderly, for which patients often self-medicate. The use of alternative medicine by individuals worldwide, including the elderly, is increasing and insomnia is a common reason for its use. Conventional treatments do not benefit all, and there is uncertainty about the effects of their long-term use. Many alternative therapies have been considered for the treatment of sleep disorders in published medical reports. These consist of pharmacological therapies, including melatonin, valerian, lavender, hops, kava, Chinese and Japanese herbal compounds, pyridoxine, St John's wort and German chamomile, and non-pharmacological therapies, including massage, acupuncture, music therapy, tai chi, magnetism and white noise. Comparison of these treatments, either with each other or with conventional therapies, is difficult because many studies inadequately define insomnia, have few subjects or lack randomization or controls. Many have not been tested specifically on elderly subjects. As a result of the problems in the trials of these treatments, drawing a definitive conclusion about the effectiveness of these therapies is difficult. Melatonin appears to be the most promising. It has been shown to produce some limited benefit by studies to date, although it has not been investigated in enough appropriate subjects to definitively conclude that there is a benefit at a sufficiently low risk. A promising role for melatonin might be in the treatment of elderly people with sleep-phase disorders. Other pharmacological treatments with potential await well-designed studies on the elderly. There are many non-pharmacological therapies that offer the potential advantages of a low side-effect profile, but the investigations of these have been even less rigorous.
... Using subacute treatment regimes, an extract made with 70% v/v ethanol affected different sleep parameters in a positive manner as well [39]. Furthermore an improvement of sleep quality comparable to treatment with 10 mg oxazepam was observed for the same ethanolic extract in two comparative studies [40,41]. Another in vivo experiment revealed a significant shortening of sleep latency in sleep-disturbed rats after treatment with a 70% ethanolic preparation [42]. ...
The genus Valeriana (Valerianaceae) contains over 250 species distributed around the world and used in traditional medicines of many cultures. The main compds. isolated from Valeriana species are essential oils, valerenic acid and its derivs. and iridoids, accumulated mainly in the roots and rhizomes. This review lists 135 chem. constituents as well as their biosynthesis and bioactivity as reported by the end of 2008 (80 refs.). [on SciFinder(R)]
... It is often taken to help alleviate insomnia. There are several clinical studies to evaluate the evidence of efficacy of valerian as a treatment for insomnia [131][132][133][134]. ...
The extensive use of herbal drugs and their multiple components and modes of action suggests that they may also cause drug interactions by changing the activity of human cytochrome P450 enzymes. The purpose of the present review is to present the available data for the top 14 herbal drug sales in the U. S. Studies describing the effects of herbal drugs on phenotyping substrates for individual CYPs were identified by a comprehensive MEDLINE search. Drugs included Allium sativum (Liliaceae), Echinacea purpurea (Asteraceae), Serenoa repens (Arecaceae), Ginkgo biloba (Ginkgoaceae), Vaccinium macrocarpon (Ericaceae), Glycine max (Fabaceae), Panax ginseng (Araliaceae), Actea racemosa (Ranunculaceae), Hypericum perforatum (Hypericaceae), Silybum marianum (Asteraceae), Camellia sinensis (Theaceae), Valeriana officinalis (Valerianaceae), Piper methysticum (Piperaceae), and Hydrastis canadensis (Ranunculaceae) preparations. We identified 70 clinical studies in 69 publications. The majority of the herbal drugs appeared to have no clear effects on most of the CYPs examined. If there was an effect, there was mild inhibition in almost all cases, as seen with garlic or kava effects on CYP2E1 and with soybean components on CYP1A2. The most pronounced effects were induction of CYP3A and other CYPs by St. John's wort and the inhibitory effect of goldenseal on CYP3A and CYP2D6, both being borderline between mild and moderate in magnitude. With the exceptions of St. John's wort and goldenseal, the information currently available suggests that concomitant intake of the herbal drugs addressed here is not a major risk for drugs that are metabolized by CYPs.
... Dorn reported on a double-blind, randomized trial of valerian extract LI 156 versus oxazepam in 75 patients with nonorganic, nonpsychiatric insomnia, 90 in which 600 mg valerian extract or 10 mg oxazepam were given daily for a month. Results of the German Sleep Questionnaire B indicated that sleep quality improved for both groups and that no differences in degree of improvement between groups were seen. ...
Insomnia and other sleep disturbances are common in cancer patients. Insomnia is a multifactorial health concern that currently affects at least 1 in 3 cancer patients, and yet most insomnia sufferers do not consult their physician regarding pharmaceutical options for relief. Use of hypnotic drugs (primarily benzodiazepines) is associated with increasing tolerance, dependence, and adverse effects on the central nervous system. While hypnotic drug use declined substantially in the past decade, the use of herbal sedatives appeared to increase. Mostly self-prescribed by lay people, herbal sedatives hold widespread appeal, presumably because of their lower cost and higher margin of safety when compared to pharmaceuticals. Studies of better-known herbal sedatives, notably valerian and kava, showed moderate evidence for both safety and efficacy for valerian while revealing disturbing toxicity concerns for kava. Milder sedatives or anxiolytics in need of clinical study include German chamomile, lavender, hops, lemon balm, and passionflower; St. John's wort may have anxiolytic effects with relevance to sleep. Herb-drug interactions are a possibility for some of these species, including St. John's wort. Although sufficient evidence exists to recommend some of these agents for short-term relief of mild insomnia, long-term trials and observational studies are needed to establish the safety of prolonged use as well as overall efficacy in the context of cancer treatment and management.
... Its efficacy has been demonstrated in a number of animal and clinical studies; however, the constituents, efficacy, and adverse effects have yet to be studied (Houghton, 1999 ). A randomized, doubleblinded , clinical study comparing valerian and oxazepam on treatment of nonorganic causes of insomnia demonstrated no differences in the efficacy of these two drugs (Dorn, 2000 ). Another study utilizing quantitative topographical electroencephalogram (EEG) showed slight but clear visible effects on the central nervous system, especially after intake of a high-dose valerian-hops mixture in healthy young adults compared to placebo (Vonderheid-Guth et al., 2000 ). ...
This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions.
In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. Settings/location: Laboratory investigation.
Mongrel cats of either gender.
Injections of the abovementioned agonists and antagonists were given.
Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded.
Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different.
The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.
... TABLE 1. (continued) Symptom CAM Therapy Evidence in Pediatrics Evidence in Adults Nonsignificant Findings Dominquez, 2000 195 Dorn, 2000 196 Ziegler, 2002 197 Wheatley, 2001 114 Passion flower Akhonzadeh et al, 2001 115 Kava Kava Gurley et al, 2005 112 Wheatley, 2001 114 Pittler and Ernst, 2003 200 Lehmann, 1996 201 Volz and Kieser, 1997 202 Emser and Bartylla, 1991 203 German Chamomile Gould, 1973 (tea), 204 Masago et al (aromatherapy), 2000 119 ...
The use of complementary/alternative medicine (CAM) has been well documented among children with cancer. This report summarizes the research evidence on the role of CAM therapies for prevention and treatment of the most commonly reported cancer-related symptoms and late effects among children with cancer. Small clinical trials document evidence of effectiveness for select therapies, such as acupuncture or ginger for nausea and vomiting, TRAUMEEL S for mucositis, and hypnosis and imagery for pain and anxiety. Several relatively small clinical trials of varying quality have been conducted on these CAM therapies in children with cancer. Some herbs have demonstrated efficacy in adults, but few studies of herbs have been conducted in children. Larger randomized clinical trials are warranted for each of these promising therapies. Until the evidence is more conclusive, the providers' role is to assess and document the child's use of CAM, critically evaluate the evidence or lack of evidence, balance the potential risks with possible benefits, and assist the family in their choices and decisions regarding use of CAM for their child with cancer.
The International Classification of Sleep Disorders defines psychophysiological insomnia as “a disorder of somatized tension and learned sleep-preventing associations that results in a complaint of insomnia and associated decreased functioning during wakefulness” (1). Psychophysiological insomnia is included under the category of primary insomnias in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (2). It is also commonly referred to as learned or conditioned insomnia and less commonly as functionally autonomous or internal arousal insomnia.
Insomnia is the most common sleep-related complaint and the second most common overall complaint (after pain) reported in primary care settings. It affects 35% of the general population, according to the 1984 report of the National Institutes of Mental Health (1). Insomnia is not defined by total sleep time but by the inability to obtain sleep of sufficient length or quality to produce refreshment the following morning. For example, a person who needs only 4 hours of sleep does not have insomnia if he or she is refreshed in the morning after having 4 hours of sleep, whereas someone who needs 10 hours of sleep may have insomnia if he or she does not feel refreshed even after 8 hours of sleep. Contrary to popular lore, psychiatric or psychological factors are not the most frequent causes of insomnia. Insomnias can be divided into two major categories: the primary insomnias and the secondary insomnias. As discussed elsewhere in this volume, primary insomnias are conditions in which the insomnia is the main pathophysiological process, whereas secondary insomnias are conditions where the insomnia is a symptom of another disorder.
Herbal medicines are becoming increasingly popular among patients because they are well tolerated and do not exert severe side effects. Nevertheless, they receive little consideration in therapeutic settings. The present article reviews the current state of research on the clinical benefits of herbal medicines on five indication groups, psychosomatic disorders, gynecological complaints, gastrointestinal disorders, urinary and upper respiratory tract infections. The study search was based on the database PubMed and concentrated on herbal medicines legally approved in Europe. After applying defined inclusion and exclusion criteria, 141 articles were selected: 59 for psychosomatic disorders (100% randomized controlled trials; RCTs), 20 for gynecological complaints (56% RCTs), 19 for gastrointestinal disorders (68% RCTs), 16 for urinary tract infections (UTI, 63% RCTs) and 24 for upper respiratory tract infections (URTI) (79% RCTs). For the majority of the studies, therapeutic benefits were evaluated by patient reported outcome measures (PROs). For psychosomatic disorders, gynecological complaints and URTI more than 80% of the study outcomes were positive, whereas the clinical benefit of herbal medicines for the treatment of UTI and gastrointestinal disorders was lower with 55%. The critical appraisal of the articles shows that there is a lack of high-quality studies and, with regard to gastrointestinal disorders, the clinical benefits of herbal medicines as a stand-alone form of therapy are unclear. According to the current state of knowledge, scientific evidence has still to be improved to allow integration of herbal medicines into guidelines and standard treatment regimens for the indications reviewed here. In addition to clinical data, real world data and outcome measures can add significant value to pave the way for herbal medicines into future therapeutic applications.
Little is known about the treatment of mild mental disorders and/or symptoms (MDS) during pregnancy. Our main purpose was to compare the use of herbal medicines during pregnancy in women with and without MDS. A questionnaire consisting of 21 multiple-choice questions was distributed in the participating obstetrics clinics or birth centers in the Canton of Zurich, in Switzerland, from August 2018 to March 2019; 398 questionnaires were considered in the analysis. The use of any type of herbal medicines–including pharmaceutical herbal products as well as teas–during pregnancy was reported by 358 women (out of 398, 89.9%). Of these, 272 participants used pharmaceutical herbal products, whereby ginger (49.2%), raspberry leaf (42.7%), bryophyllum (37.8%), chamomile (27.2%), lavender (22%) and iron-rich herbs (12.3%) were the ones most commonly mentioned. More than half (207/398, 52.0%) of all participants reported suffering from MDS during pregnancy; only a few took (synthetic) psychoactive medications (5/398, 1.3%). The percentage of use of pharmaceutical herbal medicines was higher among women reporting MDS than among the remaining women (90.0 vs 75.9%; p < 0.001). At the same time, the prevalence of MDS was higher among users of pharmaceutical herbal products than among non-users (59.6 vs 34.0%; p = 0.001). Specific questions on candidate herbal medicines for the treatment of mild MDS revealed that bryophyllum (mentioned by 107 women), lavender (56 women) and valerian (20 women) were used to reduce stress, restlessness, sleep disorders and others, in part with perceived good to very good effectiveness and tolerability. The large majority of the pregnant women participating in the survey make use of herbal medicines. The particularly high prevalence of MDS among herbal medicine-users and the very rare use of synthetic psychoactive medications suggest that pregnant women rely on herbal medicines for treatment of mild MDS. The reported good effectiveness and tolerability of a few candidate herbal medicines deserve particular attention.
Valerian (Valeriana officinalis) is a perennial flowering plant native to Europe and Asia that has had widespread use for insomnia since 400 BCE. Valerian is also used for anxiety, often in combination with other herbal products with which it has the strongest evidence. It may be beneficial for premenstrual syndrome, dysmenorrhea, menopause, postoperative cognitive impairment, restless legs syndrome, anxiety, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder (with lemon balm). In vitro, valerian shows antioxidant, cytoprotective, and neuroprotective effects. In animal research, valerian has shown antihypertensive, anxiolytic, antidepressant, and antispasmodic effects. This chapter examines some of the scientific research conducted on valerian, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of valerian’s use in treating genitourinary, neurological, psychiatric, and infectious disorders. Finally, the chapter presents a list of valerian’s Active Constituents, different Commonly Used Preparations and Dosages, and a Section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Anxiety and depression are prevalent among cancer patients, with significant negative impact. Many patients prefer herbs for symptom relief to conventional medications which have limited efficacy/side effects. We identified single-herb medicines that may warrant further study in cancer patients. Our search included PubMed, Allied and Complementary Medicine, Embase, and Cochrane databases, selecting only single-herb randomized controlled trials between 1996 and 2016 in any population for data extraction, excluding herbs with known potential for interactions with cancer treatments. One hundred articles involving 38 botanicals met our criteria. Among herbs most studied (≥6 randomized controlled trials each), lavender, passionflower, and saffron produced benefits comparable to standard anxiolytics and antidepressants. Black cohosh, chamomile, and chasteberry are also promising. Anxiety or depressive symptoms were measured in all studies, but not always as primary endpoints. Overall, 45% of studies reported positive findings with fewer adverse effects compared with conventional medications. Based on available data, black cohosh, chamomile, chasteberry, lavender, passionflower, and saffron appear useful in mitigating anxiety or depression with favorable risk–benefit profiles compared to standard treatments. These may benefit cancer patients by minimizing medication load and accompanying side effects. However, well-designed larger clinical trials are needed before these herbs can be recommended and to further assess their psycho-oncologic relevance.
Sedativa en hypnotica worden vaak gebruikt in ons land evenals in de rest van Europa en in de USA. Het gebruik betreft in overgrote meerderheid benzodiazepinen. Het benzodiazepinegebruik wordt in Nederland geschat op 7-10% van de bevolking. Bijna de helft hiervan wordt chronisch gebruikt. Opvallend is het feit dat met het stijgen van de leeftijd het gebruik toeneemt. Vrouwen blijken in alle leeftijdsgroepen twee keer zoveel benzodiazepinen te slikken dan mannen. Tenminste 40% van de benzodiazepinen wordt als hypnoticum gebruikt.
Twenty years of ongoing international controversy as to benzodiazepines, provoked by the evidence of diverse and serious adverse effects, does not yet seem to have resulted in a generalized change of attitude in the medical world. Although the data sheets for benzodiazepines now must reflect that treatment should be short and never exceed 3 months, in many cases these drugs are prescribed for much longer periods, sometimes years, without objective or subjective need. The consequences for the patient can be very negative, not only in exceptional cases but in a fair percentage of patients, especially the aged. It is imperative that primary care physicians revise their opinions as to the therapeutical pros and contras of benzodiazepines and heed the recommendations of national and international health agencies. In the U.S., U.K., France, Sweden and other countries, important groups of victims of the inadequate prescription and use of benzodiazepines are presenting claims for damages against physicians and institutions involved.
The problem of herb-drug interactions is being increasingly recognised. However, except for hypericum (Hypericum perforatum L.; St John's wort), data on drug interactions with other herbs are still inconclusive, although research has started to fill in the gaps, and knowledge is being gained about this important safety issue. This review summarises clinical data on interactions between drugs and herbal medicines, which were compiled using the following databases: MEDLINE via PubMed, Web of Science® (from their inception until March 2005) and the Cochrane Library (until 2005, issue 1). Clinical data on herb-drug interactions, observed in case reports, case series or clinical trials, were included. Results are described for the following herbs: Devil's claw (Harpagophytum procumbens D.C.), echinacea, evening primrose (Oenothera biennis L.), garlic (Allium sativum L.), ginkgo (Ginkgo biloba L.), goldenseal (Hydrastis canadensis L.), hawthorn, kava (Piper methysticum Forst.), milk thistle (Silybum marianum [L.] Gaertn.), peppermint, saw palmetto (Serenoa repens [Bartel] Small) and valerian. Information on herb-drug interactions is discussed through use of in vivo and experimental data, and conclusions are drawn when possible.
The aim of this review is to evaluate and summarize the available scientific information on the commonest plant extracts marketed in Western countries. In view of the intense, ongoing search for new plant extracts with powerful anti-inflammatory activity, we paid particular attention to this topic. The aim is to provide broad coverage of as many potentially useful plants as possible and then to focus on those with the greatest therapeutic potential.
Our bibliographic sources were the SciFinder databases: CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS (update to October 2007). In order to assess the value of clinical trials, we focused a specific search on clinical investigations concerning nine plants with the most trial data, viz., Althaea officinalis, Calendula officinalis, Centella asiatica, Echinacea purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis. This was carried out in several databases (update to June 2008): ISI Web of Knowledge(SM) (ISI WoK), SciFinder (CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS) and PubMed (indexed for MEDLINE).
Our survey covers roughly a 1000 plants, although clinical trials have been published only for 156 plants supporting specific pharmacological activities and therapeutic applications. However, for about half of the plants, in vitro and in vivo studies provide some support for therapeutic use. For one-fifth of the plants included in our search, only phytochemical studies were found. Their properties and indications were often attributed to the presence of certain compounds, but no evidence concerning the activities of the whole extracts was presented. We found that for about 12% of the plants, currently available on the Western market, no substantial studies on their properties had been published, while there was strong evidence that 1 in 200 were toxic or allergenic, so that their use ought to be discouraged or forbidden. Nine plants had considerable evidence of therapeutic effect, viz., A. officinalis, Calendula officinalis, Centella asiatica, E. purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis.
The present review provides a baseline on the level of evidence available on many herbal preparations and should be of help to those intending to research further on these topics.
The use of complementary medicines for mental health problems generates wide public interest. Patients, particularly when suffering from chronic mental health problems such as anxiety and depression, may use complementary medicines for a variety of reasons. Some may feel that a complementary approach is more “integrative” balancing mind and body; others may wish to gain control of their mental health problems. Again others may have been disappointed by conventional treatments.1 With the ubiquitous availability of knowledge in today’s high tech world, patients are increasingly well informed about treatment options. They may even be more knowledgeable about complementary medicines than clinicians whose experience in this area of practice is usually quite limited. Indeed, current professional regulations may make it extremely difficult for doctors to practise complementary medicine. Very rarely conventional treatment options, which a clinician is professionally bound to give preference, cannot be identified. Pharmacological complementary medicines are not subject to the same strict licensing requirements as conventional medicines, and commonly complementary remedies are just registered as food supplements rather than as medicinal substances.2
The range of complementary medicines is huge. Pharmacological options include herbal medicines and food supplements. These are further reviewed in this article in regard to the most common psychiatric problems encountered. Countless non-pharmacological options also exist, including acupuncture, transcutaneous electric nerve stimulation (TENS), aromatherapy, homeopathy, yoga, biofeedback, relaxation, meditation, hypnosis, reiki/therapeutic touch and reflexology. However, a review of all treatments would be beyond the scope of this review.
Evaluating the effectiveness of complementary medicines can be a daunting task. Perceived effectiveness may originate from anthropological sources describing the use of folk remedies over hundreds and sometimes even thousands of years. Many remedies have percolated this way, but systematically derived clinical evidence often remains limited (table 1). Regarding mental health problems, most of the evidence is …
Depressive disorders in comorbidity with anxiety disorders represent an frequently diagnostic and therapeutic problem. The studies quoted here prove that the symptoms associated with anxiety that severely afflict patients can be clearly improved more quickly with a combination therapy of St John's wort extract and valerian extract than with St John's wort monotherapy. The combination therapy was well tolerated, no significant side-effects occurred. Further studies are necessary to compare the combination treatment with other forms of therapy (serotonin- and noradrenalin re-uptake inhibitors).
Insomnia is the most frequently encountered sleep complaint worldwide. While many prescription drugs are used to treat insomnia, extracts of valerian (Valeriana officinalis L., Valerianaceae) are also used for the treatment of insomnia and restlessness. To determine novel mechanisms of action, radioligand binding studies were performed with valerian extracts (100% methanol, 50% methanol, dichloromethane [DCM], and petroleum ether [PE]) at the melatonin, glutamate, and GABA(A) receptors, and 8 serotonin receptor subtypes. Both DCM and PE extracts had strong binding affinity to the 5-HT(5a) receptor, but only weak binding affinity to the 5-HT(2b) and the serotonin transporter. Subsequent binding studies focused on the 5-HT(5a) receptor due to the distribution of this receptor in the suprachiasmatic nucleus of the brain, which is implicated in the sleep-wake cycle. The PE extract inhibited [(3)H]lysergic acid diethylamide (LSD) binding to the human 5-HT(5a) receptor (86% at 50 microg/ml) and the DCM extract inhibited LSD binding by 51%. Generation of an IC(50) curve for the PE extract produced a biphasic curve, thus GTP shift experiments were also performed. In the absence of GTP, the competition curve was biphasic (two affinity sites) with an IC(50) of 15.7 ng/ml for the high-affinity state and 27.7 microg/ml for the low-affinity state. The addition of GTP (100 microM) resulted in a right-hand shift of the binding curve with an IC(50) of 11.4 microg/ml. Valerenic acid, the active constituent of both extracts, had an IC(50) of 17.2 microM. These results indicate that valerian and valerenic acid are new partial agonists of the 5-HT(5a) receptor.
The use of complementary medicines in those with mental health problems is well documented. However, their effectiveness is often not established and they may be less harmless than commonly assumed.
To review the complementary medicines routinely encountered in psychiatric practice, their effectiveness, potential adverse effects and interactions.
Electronic and manual literature search on the effectiveness and safety of psychotropic complementary medicines.
Potentially useful substances include ginkgo and hydergine as cognitive enhancers, passion flower and valerian as sedatives, St John's wort and s-adenosylmethionine as antidepressants, and selenium and folate to complement antidepressants. The evidence is less conclusive for the use of omega-3 fatty acids as augmentation treatment in schizophrenia, melatonin for tardive dyskinesia and 18-methoxycoronaridine, an ibogaine derivative, for the treatment of cocaine and heroin addiction.
Systematic clinical trials are needed to test promising substances. Meanwhile, those wishing to take psychotropic complementary medicines require appropriate advice.
Efficacy and tolerability of a combined valerian/lemon balm preparation were investigated in an open, multicentre study in children less than 12 years suffering from restlessness and nervous dyskoimesis. Patients were dosed individually by the investigators. In total, 918 children were evaluated for therapeutic efficacy and tolerability. A distinct and convincing reduction in severity was found for all symptoms in the investigators' and parents' ratings. The core symptoms dyssomnia and restlessness were reduced from "moderate/severe" to "mild" or "absent" in most of the patients. In total, 80.9% of the patients who suffered from dyssomnia experienced an improvement for this symptom and 70.4% of the patients with restlessness improved clearly. For the other listed symptoms the total improvement was 37.8% on average. Both, parents and investigators assessed efficacy as to be "very good" or "good" (60.5% and 67.7%, respectively). The tolerability of Euvegal forte was considered as "good" (in 96.7% of the patients it was judged to be "very good" or "good"). No study medication-related adverse events occurred. In conclusion, Euvegal forte was effective in the treatment of younger children with restlessness and dyssomnia and it was very well tolerated.
Sleep disruption is common in the long-term care setting. This article discusses the available literature on 2 herbal approaches to sleep problems in long-term care. The largest body of evidence exists for the use of the dietary/herbal supplements valerian and melatonin. While these agents appear to have a modest positive effect on sleep quality among older adults, most studies were small in size and included only subjective assessments of sleep quality. In addition, it is unclear whether these agents pose risks to long-term care residents because of potential drug interactions. Additional research is needed before making conclusive recommendations about the use of these interventions for sleep in the long-term care setting.
Valerian is an herb that is widely available in a variety of commercial preparations and is commonly used as a sleep aid. A recent systematic review and meta-analysis of valerian concluded that evidence in support of the effectiveness of the herb was inconclusive. Therefore, in an effort to more closely examine this issue, a systematic review was conducted to examine the evidence on the efficacy of valerian as a sleep aid with specific attention to the type of preparations tested and the characteristics of the subjects studied. A comprehensive search of studies investigating valerian was conducted through computerized databases and hand searches of reference lists. Standardized forms were used to summarize findings and standardized criteria were used to assess study quality. Out of 592 articles initially identified, a total of 36 articles describing 37 separate studies met criteria for review: 29 controlled trials evaluated for both efficacy and safety, and eight open-label trials evaluated for safety only. Most studies found no significant differences between valerian and placebo either in healthy individuals or in persons with general sleep disturbance or insomnia. None of the most recent studies, which were also the most methodologically rigorous, found significant effects of valerian on sleep. Overall, the evidence, while supporting that valerian is a safe herb associated with only rare adverse events, does not support the clinical efficacy of valerian as a sleep aid for insomnia.
Sleep disorders in older patients can be caused by the changes of aging, physical disorders, psychological problems, certain drugs, or a combination of these. A complete physical examination and a thorough sleep history help in selecting appropriate treatment. Pharmacologic or surgical therapy may be needed, but one or more sleep-hygiene measures are adequate to improve most patients' quality of life when they are asleep--and awake.
This is a review and update on hypnotics. Insomnia is a symptom of many underlying conditions which have to be evaluated before resorting to medication. Hypnotics are useful for short term treatment. The benzodiazepines have replaced the barbiturates which have a low therapeutic index. The action of benzodiazepines depends on their absorption rate, lipophilicity, half-life and metabolites. They induce sleep, prolonged sleep time and reduced night wakenings. They increase stage 2 sleep, and reduce stage 1, 3, 4 and REM (Rapid Eye Movement) sleep. Flurazepam, triazolam and midaolam are described. The benzodiazepines suffer from many unwanted effects which include tolerance, dependence, withdrawal symptoms, rebound insomnia, hang over effect, alteration of memory process and synergism with ethanol. The ideal hypnotic should be free from these drawbacks. Three new generation hypnotics quazepam, zopiclone and zolpidem are described. Drugs suitable for long term hypnotic medication include antipsychotics, antidepressants and antihistamines.