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Effectiveness of Valerian on insomnia: A meta-analysis of randomized placebo-controlled trials
Abstract
Insomnia is an often seen primary health care problem. Valerian might be an alternative treatment with fewer secondary effects. The aim of this study is to evaluate its effectiveness on insomnia through a meta-analysis of published literature.
Search for randomized clinical trials (RCTs) of Valerian preparations compared with a placebo on Medline, the Cochrane Library, Embase and Biosis. Outcomes: sleep-quality improvement (SQ, yes/no), sleep-quality improvement quantified through visual analogical scales (SQS) and the latency time (LT) in minutes until getting to sleep. Three meta-analyses were carried out using inverse-variance weighted random effects models. Heterogeneity was determined with the Q-statistic and was explored through a sub-groups analysis. Publication bias was evaluated using the funnel plot.
Eighteen RCTs were selected; eight had a score of 5 on Jadad's scale. The mean differences in LT between the Valerian and placebo treatment groups was 0.70 min (95% CI, -3.44 to 4.83); the standardized mean differences between the groups measured with SQS was -0.02 (95% CI, -0.35 to 0.31); treatment with Valerian showed a relative risk of SQ of 1.37 (95% CI, 1.05-1.78) compared with the placebo group. There was heterogeneity in the three meta-analyses, but it diminished in the sub groups analysis. No publication bias was detected.
The qualitative dichotomous results suggest that valerian would be effective for a subjective improvement of insomnia, although its effectiveness has not been demonstrated with quantitative or objective measurements. We recommend future investigations oriented toward improving insomnia with other more promising treatments.
... 12 Valerenic acid has been identified as one of the primary active compounds responsible for valerian sedative properties. 13 The primary mechanism of action of valerian is believed to involve the modulation of gamma-aminobutyric acid (GABA) receptors in the brain. GABA is the main inhibitory neurotransmitter in the central nervous system, and its activation promotes relaxation and sleep. ...
... A metaanalysis of 16 randomized controlled trials (RCTs) reported that valerian improved sleep quality compared with placebo, with a standardized mean difference (SMD) of -0.70 (95% confidence interval [CI]: -1.05 to -0.35). 13 However, the authors noted significant heterogeneity among the studies and called for further research to confirm their findings. ...
... Additionally, a few meta-analyses have pooled the results of multiple studies, increased the statistical power, and provided more robust estimates of treatment effects. 7,13 However, the current evidence has several limitations. Many of these studies were small and had short durations, and they used varying dosages and formulations of the supplements, making it difficult to draw definitive conclusions. ...
Objective Herbal and natural supplements have gained popularity as alternative treatments to insomnia and sleep disorders due to their perceived safety and potential effectiveness. This literature review summarizes the current evidence on the efficacy, safety, and mechanisms of action of commonly used supplements for sleep, including valerian, hops, kava, German chamomile, cherry, tryptophan, theanine, melatonin, magnesium, and zinc.Methods We conducted literature review of clinical research on herbal and supplements for sleep reported to date. We summarized key findings and reviewed outcomes related to clinical efficacy and side effects.Results Findings suggest that certain supplements, particularly valerian, hops, and melatonin, could be effective in improving sleep quality and reducing insomnia symptoms through modulation of neurotransmitter systems and regulation of sleep-wake cycles. However, the strength of the evidence varies with unestablished optimal dosages, formulations, and treatment durations. Although generally considered safe, these supplements are not without risks, such as rare but serious adverse effects associated with kava and potential interactions with prescription medications. The quality and purity of supplements also vary widely due to a lack of strict regulations.Conclusion Healthcare providers should remain informed about the latest research and work closely with patients to develop personalized treatment plans. Herbal and natural supplements may offer promising alternatives or adjunct treatments for insomnia and sleep disorders, but their use should be guided by the best available evidence and individual patient requirements. Larger, well-designed clinical trials are needed to establish the efficacy and safety of these supplements for clinical decision-making.
... However, though these findings supported the safety of valerian, its effectiveness on sleep remains inconclusive [13]. Several systematic reviews have been performed to assess the effectiveness of valerian as a sleep aid [14][15][16][17][18]. As far back as 2000, Stevinson et al. systematically reviewed 9 RCTs and found their results were contradictory [16]. ...
... 95%CI 1.2-2.9) [17], and Fernandez-San Martin et al. also found valerian would be effective for a subjective improvement of insomnia [14]. On the contrary, Taibi et al. published a systematic review of 37 studies of valerian and reported that there were no significant differences between valerian and placebo in healthy people or people with sleep problems. ...
... These results were inconsistent with previous studies. One earlier study by Fernandez-San-Martin et al. [14] did not find improvement measured with the visual analogical scale in valerian groups compared to placebo. Furthermore, Shinjyo et al. [18] calculated the effect sizes of studies using repeated valerian administrations and found that the effects of valerian on quantifiable results of sleep quality were nonsignificant. ...
Purpose of Review
This systematic review and meta-analysis aimed to assess the effects of valerian intervention for insomnia on both subjective and objective sleep parameters.
Recent Findings
Twenty-one RCTs with a total of 1433 participants were retrieved after searching on 6 electronic databases. The results indicated that, for subjective parameters, valerian may have a small to moderate effects on PSQI score (standardized mean differences (SMD), −1.21; 95% CI [−1.92 to −0.51]), self-reported dichotomous outcome of sleep quality (risk ratio (RR) =1.37; 95% CI [1.13 to 1.68]), and self-reported sleep duration (RR=1.27; 95% CI [1.02 to 1.57]). For objective parameters, valerian only have significant effect on the length of non-rapid eye movement (NREM) stage 3 (SMD= 0.89; 95% CI [0.35 to 1.43]) of the patients. Heterogeneity was mainly due to varied study designs, especially in preparation, outcomes measured, duration of follow-up, and populations.
Summary
Valerian intervention for insomnia may improve PSQI scores, subjective dichotomous outcomes of sleep quality and duration, and time of NREM stages 3.
... Guidelines also mention phytopharmaceutical drugs for sleep disorders. A number of meta-analyses have been carried out on the topic of phytotherapy for insomnia [14][15][16], which show a slight superiority of valerian over placebo. However, the European Medical Agency (EMA) has approved a recommendation for the use of valerian in the treatment of sleep disorders based on its well-established use. ...
... GPs are advised to screen for underlying anxiety in all patients presenting with the complaint of disturbed sleep. Two simple questions can be sufficient for this purpose, as used in the GAD-2 questionnaire (feeling nervous, anxious, or on edge and not being able to stop or control worrying over the last two weeks) [15]. Silexan may be a preferable treatment option for these patients compared to Z-drugs. ...
The aim of the present study was to analyze the association between the prescription of Silexan and the recurrence of general practitioner (GP) repeat consultations because of disturbed sleep versus benzodiazepine receptor agonists including zolpidem, zopiclone, and zaleplon (Z-drugs). This retrospective cohort study was based on data from the IQVIA Disease Analyzer (DA) database. The study included adult patients treated by 1284 GPs in Germany with a documented sleep disorder and their first prescription of Silexan or Z-drug (prescription between January 2010 and October 2020). The recurrence of seeking medical advice because of sleep disorders in the 15–365 days after the first prescription was evaluated. Multivariate regression models were used, adjusted for age, sex, insurance status, and defined co-diagnoses. Data were available for 95,320 (Silexan: 5204; Z-Drug: 90,526) patients. In total, 15.6% of the Silexan patients and 28.6% of the Z-drug patients had a further documented GP consultation because of a sleep disorder. Silexan prescription was associated with significantly lower odds of recurrent sleep disorder diagnosis in the 15–365 days after the index date (Odds Ratio (OR): 0.56; 95% confidence intervals (CI): 0.51–0.60), although mental burden levels appeared higher in this group. Our study shows that the prescription of Silexan to adult patients consulting GPs for disturbed sleep results in less frequent repeat consultations than Z-drugs. This may support Silexan’s role as an efficacious, self-enabling, well-tolerated, and sustained treatment option. Because Silexan is a proven anxiolytic, its impact in improving undiagnosed anxiety disorders may have had a lasting effect for certain patients.
... In a randomized, controlled trial conducted by Aliakbari and Rafieian (2018) on eighty patients, it was shown that Valeriana officinalis improves the quality of sleep in patient with chronic heart failure [154]. However, five meta-analysis reviews published in 2000,2006,2007,2010, and 2020 revealed that the effect of V. officinalis in treating sleep problems and associated disorders might vary, and in some cases the outcomes do not support its use in treating insomnia [282][283][284][285][286]. Stevinson and Ernst (2000) analyzed nine randomized, placebo-controlled, double-blind trials measuring the effect of valerian on sleep in human participants [285]. ...
... In another meta-analysis of 37 trials, authors found in most of studies no significant differences between valerian and placebo either in healthy individuals or in persons with general sleep disturbance or insomnia [286]. The meta-analysis of 18 randomized placebo-controlled trials published by [283] showed that Valeriana spp. interventions reduced sleep latency over placebo by only 0.70 min. ...
Anxiety and insomnia are among the most common mental health disorders and are a major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O. basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies.
... The relative risk of improved sleep was 1.8 [18]. In 2010, Fernandez et al. [19] performed a meta-analysis of 18 randomized, placebo-controlled trials totaling over 1,300 participants. This study revealed that there was a significant improvement in sleep quality with valerian compared to placebo. ...
... This study revealed that there was a significant improvement in sleep quality with valerian compared to placebo. Treatment with valerian showed a relative risk of 1.37 [19]. Recently, Shinjyo et al. [20] conducted a systematic review and meta-analysis of 10 studies involving over 1,000 subjects. ...
According to the World Health Organization, there has been over 3 million deaths reported in the world due to COVID 19. In spite of an increasing number of vaccinated people across the world it is important to keep evaluating the pathophysiology of this disease and the mechanism of action for all the interventions that show improvement. Cortisol is a hormone produced by the adrenal gland that causes sequestration and apoptosis of eosinophils, monocytes and lymphocytes which lead to lymphopenia, eosinopenia and overall immunosuppression. Lymphocytes in particular form part of both the acquired and innate immune system. This commentary will evaluate some nutritional supplements that may decrease the severity of symptoms associated with COVID 19 and whether reducing cortisol can potentially be the mechanism behind decreasing the severity of COVID 19 symptoms.
... The findings in this study contrast with previous results where a nutritional intervention with a similar ingredient profile improved SOL (mean ± SD; intervention: 9.9 ± 12.3 min vs. placebo: 19.6 ± 32.0 min) in a group of healthy adult males; Halson et al., 2020). However, the differences in SOL may be attributed to the different ingredient profiles (e.g., valerian) (Fernández-San-Martín et al., 2010). Therefore, the ingredient profile in the current study may not be as effective at improving sleep in trained adult males compared to interventions with other ingredients such as valerian. ...
Athletes often experience poor sleep quality and quantity which may hinder physical performance and cognitive function. Presleep nutritional strategies may be an alternative to pharmacological interventions to improve sleep. The aim of this study was to examine the effect of two different doses of a nutritional intervention (both containing high Glycemic Index carbohydrate, whey, tryptophan, theanine, and 5′AMP) versus placebo on objective and subjective sleep, next-morning physical performance, cognitive function, and postural sway. Seventeen healthy, trained adult males completed three double-blind trials in a randomized, counterbalanced, crossover design. Participants were allocated to conditions using a Latin Square design. A (a) low-dose, (b) high-dose, or (c) placebo drink was provided 90 min before sleep each night. Polysomnography was used to measure objective sleep parameters. Cognitive function, postural sway, and subjective sleep quality were assessed 30 min after waking. Physical performance was assessed using a 10-min maximal effort cycling time trial each morning. All data were analyzed using linear mixed effects models and effect sizes were calculated using Cohen’s d . This study was registered prospectively as a clinical trial with Australian New Zealand Clinical Trials Registry (registration number: NCT05032729). No significant main effects or improvements were observed in objective or subjective sleep parameters, physical performance, cognitive function, or postural sway. The low-dose intervention appeared to reduce N3 sleep duration compared with placebo (−13.6 min). The high-dose intervention appeared to increase N1 sleep duration compared with placebo (+7.4 min). However, the magnitude of changes observed were not likely to cause meaningful reductions in sleep quality and quantity.
... In a randomized, controlled trial conducted by Aliakbari and Rafieian (2018) on eighty patients, it was shown that Valeriana officinalis improves the quality of sleep in patients with chronic heart failure [28]. However, five meta-analysis reviews published in 2000, 2006, 2007, 2010, and 2020 revealed that the effect of V. officinalis in treating sleep problems and associated disorders might vary, and in some cases, the outcomes do not support its use in treating insomnia [35][36][37]. Stevinson and Ernst (2000) analyzed nine randomized, placebo-controlled, double-blind trials measuring the effect of valerian on sleep in human participants [38]. ...
Background
Anxiety is a highly prevalent mental health issue worldwide, but it is also notably prevalent in Lebanon, where herbal medications and plants are commonly used as complementary or alternative treatments to manage anxiety. Lebanese citizens have undergone various disasters, starting with the economic crisis in 2019, the Beirut port explosion in 2020, and the COVID-19 pandemic, which led to several mental disorders such as anxiety, unipolar depression, and insomnia.
Objective
This study aimed to measure the prevalence and patterns of herbal medications and plant usage for anxiety among the Lebanese population, as well as to explore the factors influencing the decision to use herbal remedies, patient perspectives, and potential implications for mental health support.
Methods
A cross-sectional study was conducted to assess the prevalence of anxiety and the usage of herbal medications and plants among 501 Lebanese outpatients (General Population) aged 20 years and older at Lebanese community pharmacies within Beirut, Mount Lebanon, South, North, Beqaa. Data was collected through personal face-to-face and online structured interviews and surveys, capturing information on herbal medications and plants usage, sources of recommendations, patient perspectives, and perceived efficacy and safety of herbal medications and plants for anxiety.
Results
The study revealed that anxiety was a prevalent medical condition among Lebanese outpatients, with more than 50% reporting anxiety through various symptoms. Furthermore, 27.34% of Lebanese patients had consumed herbal medications, with a notable proportion advising others to use herbal remedies for anxiety. The sources of recommendations for herbal medication usage included mass media, pharmacists, and personal reading/internet. Additionally, a considerable percentage of patients expressed beliefs in the effectiveness and safety of herbal remedies for anxiety while also indicating a lack of awareness regarding potential side effects.
Conclusion
The findings of this study underscore the need for increased awareness, education, and regulatory oversight in Lebanese pharmacists regarding anxiety management using herbal medications and plant-based treatments. This includes public education campaigns, healthcare provider training, and regulatory oversight. Prioritizing patient counseling and further research is essential to assess the efficacy and safety of these treatments within the Lebanese context. This integrative approach, blending traditional practices with evidence-based mental health care, could drive policy changes and improve mental health outcomes in Lebanon.
... família Valerianaceae e a Passiflora (Passiflora incarnata) da família Passifloraceae são as plantas mais frequentemente citadas e utilizadas no tratamento da insônia. A Valeriana mostrou-se eficaz em reduzir o tempo para adormecer e melhorar a qualidade do sono em diversas populações, incluindo idosos e pacientes com insônia crônica (Fernández-San-Martín et al., 2010;Taibi et al., 2014). Ademais, a Passiflora foi associada a uma melhora significativa na qualidade do sono e na redução da ansiedade, fatores que frequentemente coexistem com a insônia (Ngan & Conduit, 2011;Grübel et al., 2014). ...
INTRODUÇÃO O uso de plantas na medicina complementar e alternativa tem raízes profundas na história da humanidade, remontando milhares de anos (Cezarotto, 2011). A insônia é um distúrbio do sono prevalente que afeta milhões de pessoas em todo o mundo, caracterizado pela dificuldade em iniciar ou manter o sono, bem como pela qualidade insatisfatória do sono. Esse distúrbio pode levar a consequências significativas na saúde física e mental, incluindo aumento do risco de doenças cardiovasculares, depressão, ansiedade e diminuição do desempenho cognitivo (Pimentel, 2009). Tradicionalmente, o tratamento da insônia inclui intervenções farmacológicas e comportamentais, mas muitas dessas abordagens apresentam limitações, como efeitos colaterais adversos e risco de dependência (Pimentel, 2009). A Fitoterapia é um tratamento terapêutico caracterizado pelo uso de plantas medicinais em suas diferentes formas farmacêuticas, sem a utilização de substâncias ativas isoladas, ainda que de origem vegetal (BRASIL, 2022), que utiliza plantas medicinais para tratar diversas condições de saúde, tem sido explorada como uma alternativa potencialmente eficaz e segura para o manejo da insônia. Inserida no contexto da Medicina Complementar Alternativa (MCA), a fitoterapia oferece uma abordagem mais natural, muitas vezes alinhada às preferências dos pacientes por tratamentos menos invasivos e com menos efeitos colaterais. Este trabalho teve como objetivo analisar o uso dos fitoterápicos Valeriana officinalis e na Passiflora incarnata para o tratamento da insônia por meio de uma Revisão Integrativa da Literatura.
... The recommended daily dosage for valerian root extract is 300-600 mg. Since VO preparations are not subject to FDA regulation, it can be challenging to set a standard for quality and strength because of variations in content and concentration (Fernández-San-Martín et al. 2010). ...
This chapter investigates the utilization of medicinal plants as a promising avenue for addressing the complex spectrum of mental health disorders, including depression, anxiety, and insomnia. The profound impact of these conditions on human well-being has fueled extensive scientific and clinical interest, prompting a search for innovative therapeutic approaches. Medicinal plants in general provide an abundant supply of bioactive substances with potential pharmacological benefits. Through a narrative exploration of the intricate mechanisms underlying their healing actions, this chapter synthesizes current research findings and ethnopharmcological perspectives to elucidate the role of herbal interventions in ameliorating mental health symptoms. It highlights the necessity for rigorous investigation, including animal studies and randomized clinical investigations, to validate the efficacy of herbal remedies and mitigate challenges associated with generalizations. By advocating for a comprehensive understanding of plant-based interventions and their modulatory effects on neurobiological pathways, this chapter aims to catalyze further research endeavors and therapeutic innovations in harnessing the therapeutic potential of nature’s pharmacopeia for enhancing mental well-being on a global scale.
... It is important to highlight that the currently existing meta-analyses emphasize the fact that there is no solid evidence regarding the effectiveness of Valerian in the insomnia´s treatment, since no controlled trial was conducted beyond six weeks, thus, there is a lack of evidence regarding its long-term safety and effectiveness. It is particularly necessary to design more robust studies about the impact of Valerian on insomnia, especially in younger individuals [50][51][52][53]. Likewise, the consumption of Melatonin for insomnia is not approved by AAMS or the FDA, and there is no evidence that its performance is superior to placebo in insomnia treatment [ 16 , 19 , 24 ]. ...
The present study aims to characterize the prevalence, the pattern of medically prescribed and over-the-counter medication/supplements in Higher Education students, as well as to relate the consumption of sleeping medication with insomnia severity, sleep effort, sleep locus of control, anxiety, and depression. Data was collected from a sample of 2029 Portuguese Higher Education students, aged ≥18 years old, being approximately 75% women and 25% men. Thirty-one percent of the sample considered suffering from insomnia, 6% consumed sleeping medication prescribed by a physician, 4% consumed OTC (over-the-counter) medication/supplements, and 2% undergone psychotherapy. Among the Higher Education students with insomnia, 19% reported consuming sleep medication prescribed by a physician, benzodiazepines were the most prescribed drug class, and the General Practitioner the physician who prescribed most frequently. Twelve percent of students with insomnia consumed OTC medication/supplements, with Valerian being the most consumed substance. Among students with insomnia, only 8% undergone psychotherapy.
... A meta-analysis of studies comparing valerian-induced subjective sleep assessment with placebo showed significant superiority over placebo. 21 Kava is a psychoactive member of the black pepper family which has long been used as a ceremonial tranquilizing drink by Pacific Island cultures, both recreationally and ritualistically. Traditionally, by grinding or pounding the kava root, the drink is prepared, then combined with water or coconut milk to be drunk before the evening meal. ...
Sedatives manage anxiety and nervous tension as they cause sedation, and sometimes a degree of analgesia, numbed consciousness with sedation, have a tendency to get sleep even at regular therapeutic doses, which distinguishes sedatives from tranquilizers. Herbs are widely used as an alternative medicine in sleep disorders. Currently insomnia is mostly managed by synthetic sedatives-hypnotics, but safety in prolonged use of synthetic sedatives and hypnotics has been raised. Over the past few years, there has been a growing propensity for herbal medicines around the world to prevent insomnia. This paper highlights the need of a natural medicine to treat insomnia and sleep disorder.
... Based on the studies carried out by Fernandez-San et al [55], using Valerian at a dose of 300mg per day for two weeks could decrease sleep latency and slow-wave sleep latency. Moreover, Mineo et al [56] reported that administration of valerian at a dose of 200mg per day for two weeks decreases night wakening and improves sleep duration. ...
Background: Insomnia is a universal health problem that affects the health and quality of life of people worldwide. During the last decade treatment of insomnia with herbal has been introduced to be effective but unfortunately, the safety and efficacy of these medicines are currently uncertain. However, the administration of various herbal medicines for insomnia is increasing mainly due to the diversity of various adverse effects of western medication. Objective: The present study is aimed to investigate available herbal medicine options for the treatment of chronic insomnia. Method: All demanded data were retrieved from electronic databases, Natural Medicines, TCMID, Natural Medicines Comprehensive Database, MedlinePlus, PubMed, EMBASE, and Google Scholar. Among them, randomized clinical trials were chosen precisely to be investigated more for seeking any additional information related to the treatment of chronic insomnia. All related papers in English and Persian languages included in the study criteria. At first, 162 articles were chosen to be investigated, then after screening all articles based on the PRISMA method, 83 qualified articles remained to be investigated carefully. Results: Herbal plants with medical properties as sedative agents are obtaining more and more attention because they contain various types of natural bioactive metabolites with the lowest rate of adverse effects. Moreover, these novel medicines are highly economic, with high efficacy while could be available easily. Conclusion: The data from this study demonstrated that medical plants could yield sedative activity and some of them are effective for insomnia, but we must not forget that further clinical trials are demanded to approve this. Keywords: Sleep disorders, Chronic insomnia, Herbal medicine, Alternative medication, Treatment.
Valeriana officinalis, commonly known as Valerian, is a perennial flowering plant that has been used for centuries in traditional medicine for its sedative and anxiolytic properties. This comprehensive study aims to explore the botanical characteristics, geographical distribution, traditional uses, chemical constituents, pharmacological activities, health benefits, recommended dosages, and potential side effects of the Valerian plant. Through a detailed examination of both historical and contemporary research, this study provides an in-depth understanding of the therapeutic potential and applications of Valerian. The pharmacological efficacy of Valerian is primarily attributed to its rich chemical composition. Key constituents include volatile oils, valepotriates, and sesquiterpenes, with valerenic acid identified as a major active compound. These components are believed to work synergistically to enhance GABAergic neurotransmission, thereby exerting sedative and anxiolytic effects on the central nervous system. Contemporary pharmacological studies have confirmed Valerian’s ability to promote relaxation, improve sleep quality, and alleviate symptoms of anxiety.
In this alphabetically arranged chapter, supplements from Tamarind through Vitex agnus-castus are discussed in detail. For each supplement, this chapter defines what it is and how it works in the body. Further, this chapter discusses the supplement’s recommended dosage as well as the evidence for or against its different usages. Safety concerns, side effects, and precautions are next discussed as well as any potential interactions with the other medications. References are provided for the data provided. The goal is for the healthcare provider to be able to reference each supplement and come away with a full, balanced, evidence-based understanding of these topics.
The intricate relationship between nutrition and psychiatric disorders has gained widespread attention in recent years, leading to the emergence of the field of nutritional psychiatry to enhance the treatment of individuals with mental health conditions. While recognizing the modifiable impact of diet on the brain, several methodological limitations persist in evaluating dietary interventions for the prevention and treatment of psychiatric disorders. This chapter focuses on the most extensively studied supplements, citing the strongest available evidence for their role and efficacy in managing psychiatric symptoms, disorders, or related conditions. The chapter provides a comprehensive summary grounded in the latest recommendations and substantiated evidence in the field. Discussed supplements encompass melatonin, omega-3 polyunsaturated fatty acids, vitamins, minerals, amino acids, probiotics, and other selected nutrients.
Sleep disorders often accompany neurological injuries, significantly impacting patient recovery and quality of life.The efficacy and adherence of traditional treatment methods have certain limitations. Exercise has been found to be a highly beneficial treatment method, capable of preventing and alleviating neurological injuries and sleep disorders. This article reviews relevant research findings from both domestic and international sources over the past few decades, systematically summarizing and analyzing the application of exercise therapy in sleep disorders,strategy of exercise intervention program and the potential molecular mechanisms by which exercise therapy improves sleep disorders. Shortcomings in current research and suggestions are presented, providing a reference for future in-depth studies on exercise interventions for sleep disorders.
Objective Sleep restfulness is closely associated with mortality. Thus, it is an important sleep-related symptom in the general population. However, it is rarely evaluated in patients with obstructive sleep apnea (OSA) syndrome. The present study examined the importance of sleep restfulness in patients with OSA receiving continuous positive airway pressure (CPAP) therapy.
Materials and Methods We administered sleep-related questionnaires, which included items such as subjective sleep duration and sleep restfulness, to 775 patients with OSA receiving CPAP therapy. Sleep restfulness was rated using a 5-point Likert-type scale, with the score of 5 indicating restfulness. Good adherence to CPAP therapy was defined as the use of CPAP therapy for at least 4 h per night in 70% of nights.
Results We excluded 105 patients with lacking data. Thus, 670 patients were finally examined. In total, 29 (4.3%), 124 (18.5%), 139 (20.8%), 235 (35.1%), and 143 (14.3%) patients answered restless (1), somewhat restless (2), neither (3), somewhat restful (4), and restful (5) respectively. A total of 467 (69.7%) patients had good adherence to CPAP therapy. Multivariate logistic regression analysis showed that sleep restfulness was independently and positively associated with subjective sleep duration (≥ 7 hours) and good adherence to CPAP therapy.
Conclusion Sleep restfulness was associated with subjective sleep duration and good adherence to CPAP therapy in patients with OSA. Favorable outcomes are significantly correlated with good adherence to CPAP therapy. Thus, sleep restfulness can be an indicator of a subtype that has favorable outcomes in patients after CPAP therapy.
This chapter presents the therapy concept for general practitioners, psychiatrists, neurologists and psychotherapists. The multimodal concept offers 30 therapy modules from the field of cognitive behavioral therapy, the third wave of behavioral therapy, the treatment basics of mind-body medicine and neurotherapy. It includes protocols, questionnaires and Information sheets as well as instructions for practical exercises that can be worked out together with the patients or given as homework. Examples of situations with patients are given, which can serve as a template and can be individually adapted in the treatment of other patients.
Insomnia is a common complaint among adults. Its prevalence rises with age and is higher in women, especially after the menopause. Potent and effective drugs are available to treat insomnia, but most prescription drugs are habit-forming and associated with morning grogginess or other side effects. Psychological treatments have been well studied and shown to have modest benefits. Many “natural” therapies have also been used to promote healthy sleep or treat insomnia. These include herbal teas and extracts, dietary supplements, and aroma therapy, but rigorous placebo-controlled randomized trials have been rare and have generally yielded little or no evidence of efficacy. Ashwagandha root has shown promise in five small, well-designed trials from India, but larger trials from other settings are necessary to confirm these findings. Warm milk, one of the most popular natural treatments, has not been studied in randomized trials. It should be, although finding a good placebo will be a challenge!
Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential‐diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep‐related breathing disorders, etc.), treatment‐resistant insomnia (A) and for other indications (B). Cognitive‐behavioural therapy for insomnia is recommended as the first‐line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in‐person or digitally (A). When cognitive‐behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low‐dose sedating antidepressants (B) can be used for the short‐term treatment of insomnia (≤ 4 weeks). Longer‐term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged‐release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast‐release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive‐behavioural therapy for insomnia (B).
Chronic insomnia disorder (simplified in this document as insomnia) is an increasingly common clinical condition in society and a frequent complaint at the offices of different areas of health practice (particularly Medicine and Psychology). This scenario has been accompanied by a significant evolution in treatment, as well as challenges in approaching patients in an appropriately way. This clinical guideline, coordinated by the Brazilian Sleep Association and the Brazilian Association of Sleep Medicine and counting on the active participation of various specialists in the area, encompasses an update on the diagnosis and treatment of insomnia in adults. To this end, it followed a structured methodology. Topics of interest related to diagnosis were written based on theoretical framework, evidence in the literature, and professional experience. As for the topics related to the treatment of insomnia, a series of questions were developed based on the PICO acronym (P – Patient, problem, or population; I – Intervention; C – Comparison, control, or comparator; O – Outcome). The work groups defined the eligible options within each of these parameters. Regarding pharmacological interventions, only the ones currently available in Brazil or possibly becoming available in the upcoming years were considered eligible. Systematic reviews were conducted to help prepare the texts and define the level of evidence for each intervention. The final result is an objective and practical document providing recommendations with the best scientific support available to professionals involved in the management of insomnia.
The incidence and prevalence of age‐related neurodegenerative dementias have been increasing. There is no curative therapy and conventional drug treatment can cause problems for patients. Medicinal plants traditionally used for problems associated with ageing are emerging as a therapeutic resource. The main aim is to give a proposal for use and future research based on scientific knowledge and tradition. A literature search was conducted in several searchable databases. The keywords used were related to neurodegenerative dementias, ageing and medicinal plants. Boolean operators and filters were used to focus the search. As a result, there is current clinical and preclinical scientific information on 49 species used in traditional medicine for ageing‐related problems, including neurodegenerative dementias. There are preclinical and clinical scientific evidences on their properties against protein aggregates in the central nervous system and their effects on neuroinflammation, apoptosis dysregulation, mitochondrial dysfunction, gabaergic, glutamatergic and dopaminergic systems alterations, monoamine oxidase alterations, serotonin depletion and oestrogenic protection. In conclusion, the potential therapeutic effect of the different medicinal plants depends on the type of neurodegenerative dementia and its stage of development, but more clinical and preclinical research is needed to find better, safer and more effective treatments.
In diesem Kapitel wird das Therapiekonzept für Hausärzte, Psychiater, Neurologen und Psychotherapeuten vorgestellt. Das multimodale Konzept offeriert 30 Therapiebausteine aus dem Bereich der kognitiven Verhaltenstherapie, der dritten Welle der Verhaltenstherapie, den Behandlungsgrundlagen der Mind-Body-Medizin sowie der Neurotherapie. Darin enthalten sind Protokolle, Fragebögen und Informationsblätter sowie Anleitungen zu praktischen Übungen, die gemeinsam mit den Patienten erarbeitet beziehungsweise als Hausaufgabe mitgegeben werden können. Geschildert werden beispielhafte Situationen mit Patienten, die als Vorlage dienen und bei der Behandlung anderer Patienten individuell angepasst werden können.
Sleep can be influenced and impaired in countless ways. Sleep disorders often severely impair quality of life and lead to high morbidity, as well as increased mortality. The indication for pharmacological treatment is based on the diagnosis of a sleep disorder, which often varies in symptoms, intensity, and duration. This chapter discusses medications for the treatment of sleep disorders and related symptoms. For more detailed information about sleep medicine diagnostics, as well as for nonpharmacological therapy modalities, please refer to the relevant sleep medical literature. We herein propose a new classification and terminology for medicines for the treatment of sleep disorders: Somnologics (lat. somnologica). With a focus on insomnia disorders, trouble falling and staying asleep, we review substances that promote sleep (anti-insomnics), either by increasing sleep pressure (somnics) or by reducing wake pressure (antivigilantics). With regards to circadian rhythm disorders, we discuss substances for the realignment of the sleep phase (chronotherapeutics). After that, medications for the treatment of hypersomnia disorders, associated with an increased need for sleep, are reviewed (antihypersomnics). Herein, we include medications for the reduction of the sleep drive (vigilantics), as well as for the treatment of cataplexy (anticataplectics).
Hypnotics are drugs that are intended to promote or improve sleep. Despite this clear definition, it is often not possible to exactly assign drugs to this group because the distinctions between sedatives, tranquilizers, and hypnotics are diffuse. None of the substances comes close to the “ideal” hypnotic, which exists only in theory. The attempt to classify hypnotics into three major groups is made: hypnotics in the classical meaning (e.g., benzodiazepines, Z-drugs, melatonin agonists), psychotropic drugs from the group of antidepressants and antipsychotics with a sedative profile, and other substances used as hypnotics (e.g., antihistamines, orexin receptor antagonists). The indications of the substances used as hypnotics are based on the classification of sleep disorders according to ICD -10 (International statistical classification of diseases) or DSM-5 (diagnostic and statistical manual of mental disorders). Further evidence-based recommendations of the guidelines on pharmacological interventions are shown and questions such as “which groups or substances are useful for which indication” are addressed. Differential indications such as the use of hypnotics in old age, in children and adolescents, as well as in pregnancy are presented with their special features.
Insomnia is a relatively common disorder, its prevalence in industrialized nations estimated to be at least 5−10%. In medically and psychiatrically ill populations, as well as in women and older age groups, the prevalence is significantly higher. Hypnotics play an important role in the treatment of short-term insomnia, although cognitive-behavioral therapy is recommended as first-line treatment. The aim of this chapter is to give an overview of recommendations for using hypnotics in the various guidelines for the clinical management of insomnia in adults. Some more recent guidelines for the treatment of insomnia also assess the various pharmacological therapy options and provide evidence-based recommendations for treatment: the European guideline for the diagnosis and treatment of insomnia of the European Sleep Research Society, the guideline of the German Association for Sleep Research and Sleep Medicine, the clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults by the American Academy of Sleep Medicine, the clinical practice guideline for the management of chronic insomnia disorder in adults from the American College of Physicians, and the consensus statement on evidence-based treatment of insomnia of the British Association for Psychopharmacology. These guidelines are presented in a comparative manner and, where reasonable and useful, current reviews are consulted.
Insomnia disorder is common in adults and children. The estimated prevalence ranges from 9% to 15% in the general population, with higher prevalence in certain subpopulations. Hypnotic medications are those that tend to produce sleep and are frequently used to treat insomnia. Commonly used hypnotics in adults include benzodiazepines (BZDs), BZD receptor agonists, antihistamines, antidepressants, melatonin receptor agonists, orexin receptor antagonists, and antipsychotics. However, hypnotic discontinuation is difficult and often unsuccessful. This article discusses strategies to discontinue hypnotics and evidence supporting their use.
Zusammenfassung
Hintergrund Phytotherapeutika werden aufgrund ihrer Beliebtheit bei PatientInnen und ihrer langen traditionellen Verwendung zunehmend in medizinische Leitlinien aufgenommen.
Methode Die vorliegende Übersichtsarbeit gibt einen systematischen Überblick über phytotherapeutische Empfehlungen und Inhalte in deutschen (AWMF) und internationalen (WFSBP, CANMAT) medizinischen Leitlinien für psychische Erkrankungen.
Ergebnisse Phytotherapeutika können bei leichten bis mittelschweren psychischen Störungen wie folgt empfohlen werden: Depressionen [(+++): Johanniskraut (Hypericum perforatum L.), (++ ): Safran (Crocus sativus L.) und Curcuma (Curcuma longa L.), (+): Lavendel (Lavandula angustifolia Mill.) und (+/–): Rosenwurz (Rhodiola rosea L.)], Angststörungen [(++ ): Lavendel und Ashwagandha (Withania somnifera (L.) Dunal), (+): Galphimia (Galphimia glauca Cav.), (+/–): Kamille (Matricaria spp.); „nicht empfohlen“ (–) wird Kava-Kava (Piper methysticum G. Forst.) wegen möglicher Lebertoxizität], Schlafstörungen [(+/–): Baldrian (Valeriana officinalis L.)] und Demenz [(+++): Ginkgo (Ginkgo biloba L.) zur Verbesserung der Kognition]. Sicherheit und Verträglichkeit wurden überwiegend als sehr gut bis tolerabel bewertet.
Schlussfolgerung Internationale Leitlinien zeigen die mögliche Vielfalt an empfehlenswerten Phytotherapeutika für die Behandlung von psychischen Erkrankungen auf. Die derzeitige Überarbeitung einer Vielzahl nationaler Leitlinien zu psychischen Erkrankungen bietet die Chance, bestehende Empfehlungen für Phytotherapeutika systematisch zu aktualisieren und neue zu integrieren, um TherapeutInnen eine evidenzbasierte Nutzen-Risiko-Bewertung für ihre PatientInnen zu ermöglichen.
The aim of this work is to review the literature on the use of herbal medicines to control dental anxiety. For this purpose, articles were searched in the databases ScienceDirect, Pubmed and The Cochrane Library. 57 articles were included in this study. The research evidence points to Valeriana officinalis and Passiflora incarnata as the most studied herbal medicines for the control of anxiety, and their adverse effects are also investigated. Studies prove the relative safety of these medications, as well as their effectiveness, low cost, lower concentration of active ingredients with better effects and fewer side effects when compared to benzodiazepines. The use of these medicinal plants requires further clarification as to their real effectiveness, correct dosage and side effects in conscious sedation in Dentistry.
Growing understanding of the finely orchestrated and integrated mechanisms governing sleep and wakefulness allow for new insights into sleep disorders and their pharmacological treatments. While sleep related conditions are many and diverse, this chapter focuses on the common ailments of insomnia and circadian rhythm disorders. We provide a brief overview of these conditions followed by a review of current pathophysiologic understandings for these conditions, which provide context to the subsequent medication review. While an in-depth review of the pharmacologic options is provided, section summaries and tables are included to allow for ease of accessibility and retrieval of the information.
Anxiety in dental patients is a problem for both dental surgeons and patients. Thus, therapies that aim to control this anxiety and thus favor the patient's collaboration during treatment become factors frequently studied in search of the best alternative for this purpose. Therefore, the objective of this work is to review in the literature the use of herbal medicines in the control of dental anxiety. The bibliographic search was carried out in the databases ScienceDirect, Web of Science, Scielo, Pubmed, The Cochrane Library. 57 articles were included in this study. Research evidence points to Valeriana officinalis and Passiflora incarnata as the most studied herbal medicines for controlling anxiety and adverse effects. Studies prove the relative safety in the use of these drugs, as well as their effectiveness, low cost, less concentration of active ingredients with better effects and lesser side effects when compared to benzodiazepines. However, the use of these medicinal plants requires further clarification as to their real effectiveness, correct dosage and side effects in conscious sedation in Dentistry.
The mental health of the older adult population requires the practitioner to invest time in understanding the life events and lifestyle of their patients in order to adequately assess and support this key area of health. Older adults often find themselves in highly stressful environments. Big life stresses such as the loss of a spouse or loved ones, financial strain, health concerns, polypharmacy, and social isolation are common and can trigger imbalances in mental health. Even in patients with previously well-managed psychological conditions, medications begin to fail, new triggers create a higher need, and additional compromise in health ignites a mental health crisis. Complementing psychotherapy with nutritional improvements, well-placed nutraceuticals, and safe movement such as Tai Chi or swimming addresses the root causes of symptoms. Paying attention to the interconnection between brain health and gut health is critical to addressing the root causes driving the inflammation, toxicity, and hormonal imbalances that lay the foundation for psychological distress. Recognizing the bidirectional information highway between the gut and the brain, the enteric nervous system with the longest nerve in the body called the vagus nerve, is the key to understanding the interconnectedness of the two and, thus, supporting healing in the seat of our psychological state, the brain. The manifestations of various imbalances in the gut, inflammatory responses, and detoxification pathways can manifest as psychological distress. The most common psychological disorders in the aging adult population are depression, anxiety, and insomnia.
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.
Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.
Background
The ZaoRenDiHuang (ZRDH) capsule is widely used in clinical practice and has significant therapeutic effects on insomnia. However, its active ingredients and mechanisms of action for insomnia remain unknown. In this study, network pharmacology was employed to elucidate the potential anti-insomnia mechanisms of ZRDH.
Methods
The potential active ingredients of ZRDH were obtained from the Traditional Chinese Medicine Systems Pharmacology Database. Possible targets were predicted using SwissTargetPrediction tools. The insomnia-related targets were identified using the therapeutic target database, Drugbank database, Online Mendelian Inheritance in Man database, and gene-disease associations database. A compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using the Metascape platform.
Results
In this study, 61 anti-insomnia components and 65 anti-insomnia targets of ZRDH were filtered through database mining. The drug-disease network was constructed with five key components. Sixty-five key targets were identified using topological analysis. Docking studies indicated that bioactive compounds could stably bind to the pockets of target proteins. Through data mining and network analysis, the GO terms and KEGG annotation suggested that the neuroactive ligand-receptor interaction, serotonergic synapse CAMP signaling, HIF−1a signaling, and toll-like receptor signaling pathways play vital roles against insomnia.
Conclusion
The potential mechanisms of ZRDH treatment for insomnia involve multiple components, targets, and pathways. These findings provide a reference for further investigations into the mechanisms underlying ZRDH treatment of insomnia.
Confronted with a complaint of insomnia, several points must be considered before prescribing a specific treatment. In particular, it is necessary to optimize the management of somatic and psychiatric comorbidities that can affect sleep and to review the intake of sleep-disrupting substances and drugs. The current guidelines for insomnia rank treatment options based on the quality of the evidence. They all agree to recommend cognitive behavioural therapy for insomnia as first-line treatment. Pharmacological treatment should only be considered if this therapy fails. We then propose to start with the drugs presenting the best safety profile before prescribing, if necessary, those having better effectiveness evidence but carrying a greater risk of side effects.
Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
El insomnio es una patología muy frecuente en la población general. Se estima que de un 10 a un 15 % de la población adulta padece insomnio crónico y que un 25 a 35 % ha sufrido un insomnio ocasional o transitorio en situaciones estresantes. El objetivo de este trabajo es proporcionar información actualizada sobre el insomnio: clasificación, causas, diagnóstico diferencial, opciones terapéuticas. Para ello hemos realizado una búsqueda en Pubmed con las palabras clave ¿insomnio¿, ¿trastornos del sueño¿ y ¿terapia farmacológica¿. La evaluación del insomnio se basa en una cuidadosa historia clínica en la que se analiza el sueño, antecedentes psiquiátricos y orgánicos personales y familiares, la toma de medicamentos y otras sustancias. Los autores coinciden en afirmar que el tratamiento debe ser primeramente etiológico y secundariamente sintomático.
The effect of acute and repeated treatment (seven days) with a valerian extract (Valdispert forte, 405 mg t.i.d.) on objective and subjective measures of sleep was studied. Polysomnography was conducted in 14 elderly poor sleepers on three nights, at one-week intervals (N0, N1, N2). N0 was an adaptation night, N1 and N2 the first and last night under treatment. Six subjects received placebo and eight subjects valerian. Subjects in the valerian group showed an increase in slow-wave sleep (SWS) and a decrease in sleep stage 1. Density of K-complexes was increased under active treatment. There was no effect on sleep onset time or time awake after sleep onset. REM sleep was unaltered. There was also no effect on self-rated sleep quality. We hypothesize that valerian increases SWS in subjects with low baseline values.
It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.
Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses.
Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews.
Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision.
In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias.
A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
Although four meta-analytic reviews support the efficacy of pharmacotherapy and behavior therapy for the treatment of insomnia, no meta-analysis has evaluated whether these treatment modalities yield comparable outcomes during acute treatment. The authors conducted a quantitative review of the literature on the outcome of the two treatments to compare the short-term efficacy of pharmacotherapy and behavioral therapy in primary insomnia.
They identified studies from 1966 through 2000 using MEDLINE, psycINFO, and bibliographies. Investigations were limited to studies using prospective measures and within-subject designs to assess the efficacy of benzodiazepines or benzodiazepine receptor agonists or behavioral treatments for primary insomnia. Benzodiazepine receptor agonists included zolpidem, zopiclone, and zaleplon. Behavioral treatments included stimulus control and sleep restriction therapies. Twenty-one studies summarizing outcomes for 470 subjects met inclusion criteria.
Weighted effect sizes for subjective measures of sleep latency, number of awakenings, wake time after sleep onset, total sleep time, and sleep quality before and after treatment were moderate to large. There were no differences in magnitude between pharmacological and behavioral treatments in any measures except latency to sleep onset. Behavior therapy resulted in a greater reduction in sleep latency than pharmacotherapy.
Overall, behavior therapy and pharmacotherapy produce similar short-term treatment outcomes in primary insomnia.
Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.
Insomnia is a common pathology in the general population. It is estimated that 10 to 15 percent of the adult population has chronic insomnia and 25 to 35 percent have suffered occasional or transient insomnia due to stressful situations. The aim of this article is to provide a review of insomnia: causes, differential diagnosis, and different options of treatment. To that end we have made a search in Pubmed with the keywords "insomnia", "sleeplessness", "sleep disorders" and "pharmacological therapy". Insomnia evaluation includes a careful sleep history, personal and family history of mental and organic illness, and a registration of drug and medication intake. Authors agree that treatment should be based primarily on etiology, and secondarily on symptomatology.
This trial was conducted as part of a project that aims to enhance public understanding and use of research in decisions about healthcare by enabling viewers to participate in research and to follow the process, through television reports and on the web. Valerian is an herbal over-the-counter drug that is widely used for insomnia. Systematic reviews have found inconsistent and inconclusive results about its effects.
Participants were recruited through a weekly nationally televised health program in Norway. Enrolment and data collection were over the Internet. 405 participants who were 18 to 75 years old and had insomnia completed a two week diary-keeping run-in period without treatment and were randomised and mailed valerian or placebo tablets for two weeks. All participants and investigators were blind to treatment until after the analysis was completed.
For the primary outcome of a minimally important improvement in self-reported sleep quality (> or = 0.5 units on a 7 point scale), the difference between the valerian group (29%) and the placebo group (21%) was not statistically significant (difference 7.5%; 95% CI-0.9 to 15.9; p = 0.08). On the global self-assessment question at the end of the treatment period 5.5% (95% CI 0.2 to 10.8) more participants in the valerian group perceived their sleep as better or much better (p = 0.04). There were similar trends favouring the valerian group for night awakenings (difference = 6.0%, 95% CI-0.5 to 12.5) and sleep duration (difference = 7.5%, 95% CI-1.0 to 16.1). There were no serious adverse events and no important or statistically significant differences in minor adverse events.
Based on this and previous studies, valerian appears to be safe, but with modest beneficial effects at most on insomnia compared to placebo. The combined use of television and the Internet in randomised trials offers opportunities to answer questions about the effects of health care interventions and to improve public understanding and use of randomised trials.
Controlled-Trials.com ISRCTN72748991.
The methodological quality of randomized controlled trials (RCTs) is commonly evaluated in order to assess the risk of biased estimates of treatment effects. The purpose of this systematic review was to identify scales used to evaluate the methodological quality of RCTs in health care research and summarize the content, construction, development, and psychometric properties of these scales.
Extensive electronic database searches, along with a manual search, were performed.
One hundred five relevant studies were identified. They accounted for 21 scales and their modifications. The majority of scales had not been rigorously developed or tested for validity and reliability. The Jadad Scale presented the best validity and reliability evidence; however, its validity for physical therapy trials has not been supported.
Many scales are used to evaluate the methodological quality of RCTs, but most of these scales have not been adequately developed and have not been adequately tested for validity and reliability. A valid and reliable scale for the assessment of the methodological quality of physical therapy trials needs to be developed.
To investigate the effectiveness of valerian for the management of chronic insomnia in general practice.
Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia.
Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their "energy level in the previous day" but poor or modest for all 24 (100%) participants' response to "total sleep time" and for 23 (96%) participants' response to "number of night awakenings" and "morning refreshment". As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P=0.06), distribution (P=1.00) or severity (P=0.46) of side effects between valerian and placebo treatments.
Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group.
Insomnia is a condition which affects millions of individuals, giving rise to emotional distress, daytime fatigue, and loss of productivity. Despite its prevalence, it has received scant clinical attention. An adequate evaluation of persistent insomnia requires detailed historical information as well as medical, psychological and psychiatric assessment. Use of a classification system for sleep disorders and familiarity with major diagnostic groups will facilitate the clinician's evaluation and treatment. Thorough assessment also requires attention to the unique aspects of presentation and specific set of etiologies which are associated with particular age groups.
The effects of 60 and 120 mg valerian (1 and 2 capsules Harmonicum Much) have been investigated by computer analysis of sleep stages (sleep profiles) and psychometric methods (questionnaires). EOG, EMG of cervical muscles, ECG and EEG (two-sided: centro-occipital and fronto-central) have been recorded from 6 male and 5 (3) female healthy volunteers. Amplified signals have been analysed on-line (power spectral analysis) and the sleep profiles have been calculated accordingly. After one night for adaptation, each subject took orally placebo, 60 and 120 mg valerian (1 and 2 capsules Harmonicum Much) according to a randomized double-blind repeated measures-design. The sleep investigations were carried out at a distance of a week for each condition (dosage per subject). In the morning following this night, the subjects completed a mood scale. Both dosages showed a decrease of sleep stage 4 and a slight reduction of REM-sleep. A slight increase of sleep stage awake, 1 and 2 could be observed. A further increase of sleep stage 3 could be identified. After application of 120 mg valerian, the frequency of REM-phases (in %) declined during the first half of the night, whereas during the second part of the night, a surplus appeared. Changes of the beta-intensity of the EEG during REM-sleep show a stronger hypnotic effect for the 120 mg dosage than for 60 mg. Maximum effect was observed between 2 and 3 hours post medication. Results of the mood scale are not different between the experimental conditions, which indicate no negative (side-) effects either from the drug or from the testing methods.
Benzodiazepines are the psychotropics most frequently prescribed despite an impressive reduction in use in the last 10 years. Their main pharmacodynamic effects (anxiolytic, sedative, anticonvulsive, muscle-relaxing, amnestic) are the basis for various therapeutic applications and indications. The most important differences among the variety of benzodiazepines are pharmacokinetic ones (elimination half-life, formation of pharmacologically active metabolites). Established indications are anxiety and sleep disorders, seizures, epilepsy, premedication and sedation in emergency medicine. In recent years it has also been proven to be effective in the treatment of panic disorder and catatonia. Among the side effects seen most frequently are impairments of cognitive and psychomotor function as well as rebound phenomena. Discussions have recently focused on the incidence of abuse and dependence as well as case reports on severe amnesia. Alternative medications like neuroleptics in low dosage and antidepressants seem to be predominantly unfavorable due to the fact that they are tolerated less well and sometimes have severe side effects. A clear-cut indication and time-limited prescription can reduce the number of benzodiazepine long-term users, and a comprehensive treatment concept must be the basis of rational prescription of benzodiazepines. The positive benefit-risk ratio as well as research perspectives [identification of receptor subtypes, development of highly selective ligands and partial (inverse) agonists] are reasons for assuming that the era of the benzodiazepines has not come to an end.
Durch die Computerklassifikation der Schlafstadien (Schlafprofil) und psychometrische Untersuchungen (Fragebogen) wurde die Wirkung von 60 und 120 mg Valepotriat (1 bzw. 2 Kapseln Harmonicum Much) auf 5 weibliche und 6 männliche gesunde Probanden im Alter von 20 bis 38 Jahren untersucht. Es wurde das EOG, das EMG der Nackenmuskulatur und das EKG sowie beidseitig zentro-okzipital und fronto-zentral das EEG abgeleitet. Die verstärkten Signale wurden on-line vorausgewertet (Powerspektrum) und daraus das Schlafprofil berechnet.
Nach Vorschalten einer Adaptionsnacht applizierten wir jeder Versuchsperson randomisiert und doppelblind oral je einmal Plazebo, 60 und 120 mg Valepotriat. Die Schlafuntersuchungen wurden im Abstand von je einer Woche durchgeführt. Am folgenden Morgen nahmen wir das subjektive Befinden über einen Fragebogen auf. Die Untersuchungen ergaben, daß beide Dosierungen das Stadium 4 stärker und die REM-Aktivität schwach reduzieren. Demgegenüber war eine leichte Zunahme der Stadien Wach, 1 und 2 zu erkennen. Eine stärkere Zunahme konnte für Stadium 3 nachgewiesen werden.
Nach Applikation der 120 mg Dosis reduzierte sich in der ersten Nachthälfte der prozentuale Anteil der REM-Aktivität, um in der zweiten Nachthälfte in einen leichten Überschuß überzugehen.
Die Veränderungen der β-lntensität während der REM-Phasen weisen bei der 60 mg Dosierung auf schwächere und bei der 120 mg Dosis auf eine stärkere hypnotische Wirkung hin. Das Wirkungsmaximum lag zwischen 2 und 3 Stunden.
Die Auswertung der Befindlichkeit mittels Fragebogen ergab, daß - von der Adaptionsnacht abgesehen - keine Versuchsbeeinflussung vorlag und die untersuchte Substanz keinerlei unangenehme Nachwirkungen hatte.
OBJECTIVE: To measure the prevalence of sleep problems in a working population and examine their association with health problems, health-related
quality-of-life measures, work-related problems, and medical expenditures. Also, to explore the usefulness of a sleep-problems
screen for mental health conditions and underlying sleep disorders.
DESIGN: Cross-sectional survey administered via voice mail and telephone interview.
SETTING: A San Francisco Bay Area telecommunications firm.
PARTICIPANTS: Volunteer sample of 588 employees who worked for a minimum of six months at the company and were enrolled in its fee-for-service
health plan.
MEASUREMENTS AND MAIN RESULTS: Thirty percent of respondents reported currently experiencing sleep problems and were found to have worse functioning and
well-being (general health, cognitive functioning, energy), more work-related problems (decreased job performance and lower
satisfaction, increased absenteeism), and a greater likelihood of comorbid physical and mental health conditions than were
the respondents who did not have sleep problems. They also demonstrated a trend toward higher medical expenditures.
CONCLUSIONS: Self-perceived sleep problems were common among the respondents and were associated with poorer health and health-related
quality of life. A single question about sleep problems may serve as an effective screen for identifying primary care patients
with mental health problems, as well as underlying sleep disorders.
As part of the National Institute of Mental Health Epidemiologic Catchment Area study, 7954 respondents were questioned at baseline and 1 year later about sleep complaints and psychiatric symptoms using the Diagnostic Interview Schedule. Of this community sample, 10.2% and 3.2% noted insomnia and hypersomnia, respectively, at the first interview. Forty percent of those with insomnia and 46.5% of those with hypersomnia had a psychiatric disorder compared with 16.4% of those with no sleep complaints. The risk of developing new major depression was much higher in those who had insomnia at both interviews compared with those without insomnia (odds ratio, 39.8; 95% confidence interval, 19.8 to 80.0). The risk of developing new major depression was much less for those who had insomnia that had resolved by the second visit (odds ratio, 1.6; 95% confidence interval, 0.5 to 5.3). Further research is needed to determine if early recognition and treatment of sleep disturbances can prevent future psychiatric disorders.
The effect of an aqueous extract of valerian root on sleep was studied in two groups of healthy, young subjects. One group (N = 10) slept at home, the other (N = 8) in the sleep laboratory. Sleep was evaluated on the basis of questionnaires, self-rating scales and night-time motor activity. In addition, polygraphic sleep recordings and spectral analysis of the sleep EEG was performed in the laboratory group. Under home conditions, both doses of valerian extract (450 and 900 mg) reduced perceived sleep latency and wake time after sleep onset. Night-time motor activity was enhanced in the middle third of the night and reduced in the last third. The data suggest a dose-dependent effect. In the sleep laboratory, where only the higher dose of valerian was tested, no significant differences from placebo were obtained. However, the direction of the changes in the subjective and objective measures of sleep latency and wake time after sleep onset, as well as in night-time motor activity, corresponded to that observed under home conditions. There was no evidence for a change in sleep stages and EEG spectra. The results indicate that the aqueous valerian extract exerts a mild hypnotic action.
In quantifying the effects of mild sedatives both physiological and subjective aspects of sleep must be taken into account. A questionnaire analysis on a mild sedative (400 mg of an aqueous extract of Valeriana officinalis L.) showed that by subjective criteria it is sedative (i.e. it significantly decreased perceived sleep latencies and night awakenings, and improved sleep quality). In an EEG study on the same preparation the pattern of results tended to confirm the subjective evaluation (i.e. shorter mean sleep latency, increased mean latency to first awakening) but the changes did not reach statistical significance. The discussion critically examines some of the approaches used to test putative mild sedatives and suggests a rational approach to analysing their effects.
The effect of an aqueous extract of valerian (Valeriana officinalis L.) root on subjectively rated sleep measures was studied on 128 people. Each person received 9 samples to test (3 containing placebo, 3 containing 400 mg valerian extract and 3 containing a proprietary over-the-counter valerian preparation). The samples, identified only by a code number, and presented in random order, were taken on non-consecutive nights. Valerian produced a significant decrease in subjectively evaluated sleep latency scores and a significant improvement in sleep quality: the latter was most notable among people who considered themselves poor or irregular sleepers, smokers, and people who thought they normally had long sleep latencies. Night awakenings, dream recall and somnolence the next morning were relatively unaffected by valerian. With the proprietary valerian-containing preparation, the only change was a significant increase in reports of feeling more sleepy than normal the next morning. Thus the questionnaire, simple to use and non-invasive, provides a sensitive means for detecting the effects of mild sedatives on different aspects of sleep in man. It also allows identification within the test population of the subgroups most affected.
A large and increasing number of patients use medicinal herbs or seek the advice of their physician regarding their use. More than one third of Americans use herbs for health purposes, yet patients (and physicians) often lack accurate information about the safety and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to help patients make wise decisions about their use. This article provides a review of the data on 12 of the most commonly used herbs in the United States. In addition, we provide practical information and guidelines for the judicious use of medicinal herbs.
Insomnia is a prevalent health complaint in older adults. Behavioral and pharmacological treatments have their benefits and limitations, but no placebo-controlled study has compared their separate and combined effects for late-life insomnia.
To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for late-life insomnia.
Randomized, placebo-controlled clinical trial, at a single academic medical center. Outpatient treatment lasted 8 weeks with follow-ups conducted at 3, 12, and 24 months.
Seventy-eight adults (50 women, 28 men; mean age, 65 years) with chronic and primary insomnia.
Cognitive-behavior therapy (stimulus control, sleep restriction, sleep hygiene, and cognitive therapy) (n = 18), pharmacotherapy (temazepam) (n = 20), or both (n = 20) compared with placebo (n = 20).
Time awake after sleep onset and sleep efficiency as measured by sleep diaries and polysomnography; clinical ratings from subjects, significant others, and clinicians.
The 3 active treatments were more effective than placebo at posttreatment assessment; there was a trend for the combined approach to improve sleep more than either of its 2 single components (shorter time awake after sleep onset by sleep diary and polysomnography). For example, the percentage reductions of time awake after sleep onset was highest for the combined condition (63.5%), followed by cognitive-behavior therapy (55%), pharmacotherapy (46.5%), and placebo (16.9%). Subjects treated with behavior therapy sustained their clinical gains at follow-up, whereas those treated with drug therapy alone did not. Long-term outcome of the combined intervention was more variable. Behavioral treatment, singly or combined, was rated by subjects, significant others, and clinicians as more effective than drug therapy alone. Subjects were also more satisfied with the behavioral approach.
Behavioral and pharmacological approaches are effective for the short-term management of insomnia in late life; sleep improvements are better sustained over time with behavioral treatment.
To determine the prevalence and characteristics of insomnia in primary care patients, to examine patients' help-seeking behavior, and to compare the frequency of insomnia in primary care patients to the general population.
286 patients from primary care clinics in San Diego, California (n = 96), and in Haleiwa and Honolulu, Hawaii (n = 190) participated. Sleep study questionnaires were distributed by front desk receptionists to all patients over 18 years of age upon arrival at the clinic for an appointment with the physician. Completed questionnaires were collected at the clinic or returned by mail. Comparisons were made by using nonparametric statistics. A logistic regression analysis using backward elimination was done to develop a model showing predictors of who would consult with the physician about a sleep problem.
The prevalence of insomnia in primary care patients was 69%, with 50% reporting occasional insomnia and 19% reporting chronic insomnia. As expected, patients with chronic insomnia had the most severe sleep complaints as well as the poorest daytime functioning, and exhibited the most help-seeking behaviors. The four predictors of discussing insomnia with a physician were how patients felt physically, number of years of insomnia, age, and income.
The primary care population has a higher prevalence of insomnia than the general population, probably because of concomitant psychiatric and medical illnesses. Although many of the characteristics of the sleep complaints are easily detected, most patients with insomnia are not treated effectively.
The underground organs of members of the genus Valeriana (Valerianaceae), as well as related genera such as Nardostachys, are used in the traditional medicine of many cultures as mild sedatives and tranquillizers and to aid the induction of sleep. V. officinalis is the species most commonly used in northern Europe and still retains its official pharmaco-poeial status although it is most commonly encountered as an ingredient of herbal medicines. This plant is still the subject of considerable research aimed at establishing the chemical and pharmacological basis of the activity which has been clearly shown in a number of animal and clinical studies.
The constituents of the volatile oil are very variable due to population differences in genetics and to environmental factors. The major constituents include the monoterpene bornyl acetate and the sesquiterpene valerenic acid, which is characteristic of the species, in addition to other types of sesquiterpene. Some of these have been shown to have a direct action on the amygdaloid body of the brain and valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain resulting in sedation. The non-volatile monoterpenes known as valepotriates were first isolated in 1966 and contribute to the overall activity by possessing sedative activity based on the CNS although the mode of action is not clearly known. The valepotriates themselves act as prodrugs which are transformed into homobaldrinal which has been shown to reduce the spontaneous motility of mice. More recent studies have shown that aqueous extracts of the roots contain appreciable amounts of GABA which could directly cause sedation but there is some controversy surrounding the bioavailability of this compound. Another recent finding is the presence of a lignan, hydroxypinoresinol, and its ability to bind to benzodiazepine receptors.
Valerian is a good example of both the negative and positive aspects of herbal drugs. The considerable variation in its composition and content as well as the instability of some of its constituents pose serious problems for standardization but the range of components which contribute to its overall activity suggest that it may correct a variety of underlying causes of conditions which necessitate a general sedative or tranquillizing effect.
A randomised, controlled, double-blind trial was performed on 102 male and female volunteers to determine whether reaction time, alertness and concentration might be impaired by treatment with a native valerian root extract (VRE). The effect was first examined the morning after a single evening dose of VRE (600 mg LI 156) vs. flunitrazepam (FNZ) (1 mg) and placebo (PL) (trial section A), and then after two weeks of evening administration of VRE (600 mg LI 156) vs. PL (trial section B). 99 volunteers were analysed in section A and 91 in section B. The primary criterion was the median of reaction time (MRT) measured with the Vienna Determination Test. Secondary criteria were cognitrones (alertness test), tracking test (two-handed co-ordination), sleep quality (VIS-A, Vis-M), further VDT parameters, and safety criteria. The single administration of LI 156 did not impair the reaction abilities, concentration and co-ordination. After 14 days of treatment, the equivalence of VRE and PL was proven by confirmative analysis concerning the improvement of MRT (p = 0.4481). Evaluation of the secondary criteria were consistent with the results of the primary criterion. It is concluded that neither single nor repeated evening administrations of 600 mg of VRE have a relevant negative impact on reaction time, alertness and concentration the morning after intake.
Insomnia is a condition which affects millions of individuals, giving rise to emotional distress, daytime fatigue, and loss of productivity. Despite its prevalence, it has received scant clinical attention. An adequate evaluation of persistent insomnia requires detailed historical information as well as medical, psychological and psychiatric assessment. Use of a classification system for sleep disorders and familiarity with major diagnostic groups will facilitate the clinician's evaluation and treatment. Thorough assessment also requires attention to the unique aspects of presentation and specific set of etiologies which are associated with particular age groups.
A carefully designed study assessed the short-term (single dose) and long-term (14 days with multiple dosage) effects of a valerian extract on both objective and subjective sleep parameters. The investigation was performed as a randomised, double-blind, placebo-controlled, cross-over study. Sixteen patients (4 male, 12 female) with previously established psychophysiological insomnia (ICSD-code 1.A.1.), and with a median age of 49 (range: 22 to 55), were included in the study. The main inclusion criteria were reported primary insomnia according to ICSD criteria, which was confirmed by polysomnographic recording, and the absence of acute diseases. During the study, the patients underwent 8 polysomnographic recordings: i.e., 2 recordings (baseline and study night) at each time point at which the short and long-term effects of placebo and valerian were tested. The target variable of the study was sleep efficiency. Other parameters describing objective sleep structure were the usual features of sleep-stage analysis, based on the rules of Rechtschaffen and Kales (1968), and the arousal index (scored according to ASDA criteria, 1992) as a sleep microstructure parameter. Subjective parameters such as sleep quality, morning feeling, daytime performance, subjectively perceived duration of sleep latency, and sleep period time were assessed by means of questionnaires. After a single dose of valerian, no effects on sleep structure and subjective sleep assessment were observed. After multiple-dose treatment, sleep efficiency showed a significant increase for both the placebo and the valerian condition in comparison with baseline polysomnography. We confirmed significant differences between valerian and placebo for parameters describing slow-wave sleep. In comparison with the placebo, slow-wave sleep latency was reduced after administration of valerian (21.3 vs. 13.5 min respectively, p<0.05). The SWS percentage of time in bed (TIB) was increased after long-term valerian treatment, in comparison to baseline (9.8 vs. 8.1% respectively, p<0.05). At the same time point, a tendency for shorter subjective sleep latency, as well as a higher correlation coefficient between subjective and objective sleep latencies, were observed under valerian treatment. Other improvements in sleep structure - such as an increase in REM percentage and a decrease in NREM1 percentage - took place simultaneously under placebo and valerian treatment. A remarkable finding of the study was the extremely low number of adverse events during the valerian treatment periods (3 vs. 18 in the placebo period). In conclusion, treatment with a herbal extract of radix valerianae demonstrated positive effects on sleep structure and sleep perception of insomnia patients, and can therefore be recommended for the treatment of patients with mild psychophysiological insomnia.
Objective: To systematically review the evidence for the effects of the herb valerian (Valeriana officinalis) on insomnia, based on randomized, placebo-controlled, double-blind trials.Background: Valerian has long been advocated and used for promoting sleep but until quite recently evidence was solely anecdotal. However, during the last two decades a number of clinical trials have been conducted.Materials and methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the effect of valerian monopreparations on sleep in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.Results: Nine trials were located meeting the selection criteria. The findings of the studies were contradictory and there was great inconsistency between trials in terms of patients, experimental design and procedures and methodological quality.Conclusion: The evidence for valerian as a treatment for insomnia is inconclusive. There is a need for rigorous trials to determine its efficacy.
The authors studied the sleep of patients with insomnia who complained of poor sleep despite chronic use of benzodiazepines (BZDs). The sample consisted of 19 patients (mean age 43.3+/-10.6 years) with primary insomnia (DSM-IV), who had taken BZDs nightly, for 7.1+/-5.4 years. The control group was composed of 18 healthy individuals (mean age 37+/-8 years). Sleep electroencephalogram (EEG) of the patients was analyzed with period amplitude analysis (PAA) and associated algorithms, during chronic BZD use (Night 1), and after 15 days of a valerian placebo trial (initiated after washout of BZD, Night 2). Sleep of control subjects was monitored in parallel.
Valerian subjects reported significantly better subjective sleep quality than placebo ones, after BZD withdrawal, despite the presence of a few side effects. However, some of the differences found in sleep structure between Night 1 and Night 2 in both the valerian and placebo groups may be due to the sleep recovery process after BZD washout. Example of this are: the decrease in Sleep Stage 2 and in sigma count; the increase in slow-wave sleep (SWS), and delta count, which were found to be altered by BZD ingestion. There was a significant decrease in wake time after sleep onset (WASO) in valerian subjects when compared to placebo subjects; results were similar to normal controls. Nonetheless, valerian-treated patients also presented longer sleep latency and increased alpha count in SWS than control subjects.
The decrease in WASO associated with the mild anxiolytic effect of valerian appeared to be the major contributor to subjective sleep quality improvement found after 2-week of treatment in insomniacs who had withdrawn from BDZs. Despite subjective improvement, sleep data showed that valerian did not produce faster sleep onset; the increase in alpha count compared with normal controls may point to residual hyperarousabilty, which is known to play a role in insomnia. Nonetheless, we lack data on the extent to which a sedative drug can improve alpha sleep EEG. Thus, the authors suggest that valerian had a positive effect on withdrawal from BDZ use.
Serious sleep problems are common in children with an intellectual deficit (ID), and are often the source of much distress for both the child and caregivers. As yet, no satisfactory long-term treatment exists for intransigent sleep difficulties in children with an ID. Valerian, Valeriana spp., has been used for thousands of years to induce relaxation and sleep. Scientific investigation of valerian's sleep promoting ability in humans, whilst limited, has yielded promising findings. This initial study aimed to explore valerian's potential for assisting in the treatment of sleep problems in children with an ID. Five children with varying intellectual deficits and different primary sleep problems underwent eight continuous weeks of monitoring via sleep diaries, adhering to a double blind, placebo controlled and randomised design. Compared to baseline and placebo, valerian treatment led to significant reductions in sleep latencies and nocturnal time awake, lengthened total sleep time and improved sleep quality. The treatment was apparently most effective in children with deficits that involved hyperactivity. Although the findings are preliminary and in need of replication, there is evidence to suggest that valerian may be useful in the safe and effective long-term treatment of intransigent sleep difficulties in children with ID's, and therefore warrants further investigation.
Valerian is a traditional herbal sleep remedy that has been studied with a variety of methodologic designs using multiple dosages and preparations. Research has focused on subjective evaluations of sleep patterns, particularly sleep latency, and study populations have primarily consisted of self-described poor sleepers. Valerian improves subjective experiences of sleep when taken nightly over one- to two-week periods, and it appears to be a safe sedative/hypnotic choice in patients with mild to moderate insomnia. The evidence for single-dose effect is contradictory. Valerian is also used in patients with mild anxiety, but the data supporting this indication are limited. Although the adverse effect profile and tolerability of this herb are excellent, long-term safety studies are lacking.
Passage of the Dietary Supplement Health and Education Act in 1994 restricted the Food and Drug Administration's control over dietary supplements, leading to enormous growth in their promotion. The Internet is often used by consumers as a source of information on such therapies.
To assess the information presented and indications claimed on the Internet for the 8 best-selling herbal products.
We searched the Internet using the 5 most commonly used search engines. For each, we entered the names of the 8 most widely used herbal supplements (ginkgo biloba, St John's wort, echinacea, ginseng, garlic, saw palmetto, kava kava, and valerian root). We analyzed the health content of all Web sites listed on the first page of the search results.
We analyzed all accessible, English-language Web sites that pertained to oral herbal supplements. A total of 522 Web sites were identified; of these, 443 sites met inclusion criteria for the analysis.
The nature of the Web site (retail or nonretail), whether it was a sponsored link, and all references, indications, claims, and disclaimers were recorded. Two reviewers independently categorized medical claims as disease or nondisease according to Food and Drug Administration criteria.
Among 443 Web sites, 338 (76%) were retail sites either selling product or directly linked to a vendor. A total of 273 (81%) of the 338 retail Web sites made 1 or more health claims; of these, 149 (55%) claimed to treat, prevent, diagnose, or cure specific diseases. More than half (153/292; 52%) of sites with a health claim omitted the standard federal disclaimer. Nonretail sites were more likely than retail sites to include literature references, although only 52 (12%) of the 443 Web sites provided referenced information without a link to a distributor or vendor.
Consumers may be misled by vendors' claims that herbal products can treat, prevent, diagnose, or cure specific diseases, despite regulations prohibiting such statements. Physicians should be aware of this widespread and easily accessible information. More effective regulation is required to put this class of therapeutics on the same evidence-based footing as other medicinal products.
Placebo interventions are often claimed to improve patient-reported and observer-reported outcomes, but this belief is not based on evidence from randomised trials that compare placebo with no treatment.
To assess the effect of placebo interventions.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2002), MEDLINE (1966 to 2002), EMBASE (1980 to 2002), Biological Abstracts (1986 to 2002), and PsycLIT (1887 to 2002). We contacted experts on placebo research, and read references in the included trials.
We included randomised placebo trials with a no-treatment control group investigating any health problem.
Two reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information.
Outcome data were available in 156 out of 182 included trials, investigating 46 clinical conditions. We found no statistically significant pooled effect of placebo in 38 studies with binary outcomes (4284 patients), relative risk 0.95 (95% confidence interval (CI) 0.89 to 1.01). The pooled relative risk for patient-reported outcomes was 0.95 (95% CI 0.88 to 1.03) and for observer-reported outcomes 0.91 (95% CI 0.81 to 1.03). There was heterogeneity (P=0.01) but the funnel plot was symmetrical. There was no statistically significant effect of placebo interventions in the four clinical conditions investigated in three trials or more: pain, nausea, smoking, and depression, but confidence intervals were wide. We found an overall effect of placebo treatments in 118 trials with continuous outcomes (7453 patients), standardised mean difference (SMD) -0.24 (95% CI -0.31 to -0.17). The SMD for patient-reported outcomes was -0.30 (95% CI -0.38 to -0.21), whereas no statistically significant effect was found for observer-reported outcomes, SMD -0.10 (95% CI -0.20 to -0.01). There was heterogeneity (P<0.001) and large variability in funnel plot results even for big trials. There was an apparent effect of placebo interventions on pain (SMD -0.25 (95% CI -0.35 to-0.16)), and phobia (SMD -0.63 (95% CI -1.17 to -0.08)); but also a substantial risk of bias. There was no statistically significant effect of placebo interventions in eight other clinical conditions investigated in three trials or more: nausea, smoking, depression, overweight, asthma, hypertension, insomnia and anxiety, but confidence intervals were wide.
There was no evidence that placebo interventions in general have clinically important effects. A possible small effect on continuous patient-reported outcomes, especially pain, could not be clearly distinguished from bias.
One of the most popular herbal remedies for the alleviation of sleep problems is valerian. However, research into valerian is sparse, and studies differ greatly with respect to design, measures, and preparations used. This clinical study used standardized sleep EEG and psychometric tests to evaluate the clinical efficacy of a valerian preparation (Li 156).
A placebo‐controlled three way crossover clinical trial was completed using 16 (5 male and 11 female) sleep‐disturbed participants (aged 50 to 64 years, mean age 55.9, SD 4.68). Participants slept overnight in a sleep laboratory, following a 21:00 hours dose of valerian 300 mg, valerian 600 mg, or placebo (double‐blind). EEG sleep was recorded for each participant at 23:00 hours until 07:00 hours, when a psychometric evaluation was performed the morning after dose. Test periods were separated by six days washout period.
Results showed no significant effect between valerian 300 mg, valerian 600 mg or placebo on any EEG parameter or psychometric measure. This suggests valerian at these doses is ineffective as an acute dose for sleep problems. However, valerian is widely used, and is traditionally sedative. Therefore, more research is required into therapeutic dose, types of valerian preparation, and the optimum period of use for therapeutic effect. Copyright © 2004 John Wiley & Sons, Ltd.
Initially thought to be virtually free of negative effects, benzodiazepines are now known to carry risks of dependence, withdrawal, and negative side effects. Among the most controversial of these side effects are cognitive effects. Long-term treatment with benzodiazepines has been described as causing impairment in several cognitive domains, such as visuospatial ability, speed of processing, and verbal learning. Conversely, long-term benzodiazepine use has also been described as causing no chronic cognitive impairment, with any cognitive dysfunction in patients ascribed to sedation or inattention or considered temporary and associated with peak plasma levels. Complicating the issue are whether anxiety disorders themselves are associated with cognitive deficits and the extent to which patients are aware of their own cognitive problems. In an attempt to settle this debate, meta-analyses of peer-reviewed studies were conducted and found that cognitive dysfunction did in fact occur in patients treated long term with benzodiazepines, and although cognitive dysfunction improved after benzodiazepines were withdrawn, patients did not return to levels of functioning that matched benzodiazepine-free controls. Neuroimaging studies have found transient changes in the brain after benzodiazepine administration but no brain abnormalities in patients treated long term with benzodiazepines. Such findings suggest that patients should be advised of potential cognitive effects when treated long term with benzodiazepines, although they should also be informed that the impact of such effects may be insignificant in the daily functioning of most patients.
The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.
A group of 8 volunteers suffering from mild insomnia received a placebo, 450 mg or 900 mg of an aqueous extract of valerian root in a double-blind, repeated measures, random-order design. Subjective sleep ratings were assessed by questionnaire and movements were recorded throughout the night with wrist-worn activity meters. Using the first period of 5 consecutive minutes without movement as a criterion of sleep onset, there was a significant decrease in sleep latency with 450 mg valerian compared to placebo (15.8 +/- 2.2 min vs 9.0 +/- 1.5 min; paired "t" = 3.37;p < 0.01). The higher dose of valerian produced no further improvement in sleep latency.
Valerian and hops are traditionally used as sleep aids. Since the fixed extract combination (Ze 91019) as a whole is considered the active compound, the clinical efficacy must be demonstrated for this extract combination. The present clinical study aimed to demonstrate superiority of the fixed extract combination in comparison with placebo in patients suffering from non-organic insomnia (ICD 10, F 51.0-51.2). Objective sleep parameters were registered by means of a transportable home recorder system (QUISI). The primary outcome was the reduction in sleep latency (SL2) which had to be prolonged at baseline (>/=30 min) as an inclusion criteria. The treatment period lasted for 4 weeks with either placebo, single valerian extract (Ze 911) or the fixed valerian hops extract combination (Ze 91019). The amount of the single valerian extract was identical to that amount contained in the fixed extract combination, i.e. 500 mg valerian extract siccum. In the extract combination 120 mg hops extract siccum was added. Both the extracts were prepared with 45% methanol m/m with a drug-extract ratio of 5.3:1 (valerian) and 6.6:1 (hops), respectively. The fixed extract combination was significantly superior to the placebo in reducing the sleep latency whilst the single valerian extract failed to be superior to the placebo. The result underlined the plausibility for adding hops extract to the valerian extract.
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.
Complementary and alternative medicines (CAM) are frequently used for the treatment of sleep disorders, but in many cases patients do not discuss these therapies directly with their health care provider. There is a growing body of well-designed clinical trials using CAM that have shown the following: (1) Melatonin is an effective agent for the treatment of circadian phase disorders that affect sleep; however, the role of melatonin in the treatment of primary or secondary insomnia is less well established. (2) Valerian has shown a benefit in some, but not all clinical trials. (3) Several other modalities, such as Tai Chi, acupuncture, acupressure, yoga, and meditation have improved sleep parameters in a limited number of early trials. Future work examining CAM has the potential to significantly add to our treatment options for sleep disorders in older adults.
Insomnia affects a large percentage of the population, particularly the elderly. Literature reports varying estimates of prevalence, a variation that relates to the lack of definition and consistency in diagnostic criteria. Primary insomnia (not caused by known physical/mental conditions) responds to pharmacologic therapy, while secondary insomnia(resulting from other illnesses, medications, or sleep disorders) responds to pharmacologic and psychologic treatments (cognitive therapy, relaxation techniques, stimulus control). Use of certain agents in the elderly and patients with abuse/addiction potential is a concern. Medicare Part D does not cover benzodiazepines (classified as controlled substances). Nonprescription agents are affordable but have sedation and anticholinergic side effects. Medication use should be considered a possible contributing factor. Insomnia patients experience significantly more limited activity and higher total health services than those without insomnia. Annual costs are between 107.5 billion. A standard definition and better pathways to recognize and treat insomnia are needed.
To test the effects of nightly valerian (Valeriana officinalis) extract to improve sleep of older women with insomnia.
Participants in this phase 2 randomized, double-blind, crossover controlled trial were 16 older women (mean age=69.4+/-8.1 years) with insomnia. Participants took 300 mg of concentrated valerian extract or placebo 30 min before bedtime for 2 weeks. Sleep was assessed in the laboratory by self-report and polysomnography (PSG) at baseline and again at the beginning and end of each treatment phase (total of nine nights in the laboratory) and at home by daily sleep logs and actigraphy.
There were no statistically significant differences between valerian and placebo after a single dose or after 2 weeks of nightly dosing on any measure of sleep latency, wake after sleep onset (WASO), sleep efficiency, and self-rated sleep quality. In comparing each treatment to baseline in separate comparisons, WASO significantly increased (+17.7+/-25.6 min, p=.02) after 2 weeks of nightly valerian, but not after placebo (+6.8+/-26.4 min, NS). Side effects were minor and did not differ significantly between valerian and placebo.
Valerian did not improve sleep in this sample of older women with insomnia. Findings from this study add to the scientific evidence that does not support use of valerian in the clinical management of insomnia.