The efficacy and safety of herbal medicine for insomnia in adults: an overview of recent research.
Insomnia is estimated to affect about one-third of all adults of whom 6-10% meet the criteria for insomnia disorder. (1) Common features include: difficulty falling asleep causing reduced sleep latency time (LT); several awakenings during the night and/or early morning awakening; all resulting in non-restorative and poor sleep quality (SQ). (2) Insomnia disorder is defined by these key features occurring at least three nights a week over the course of one month and causing significant impairment to daytime functioning. (1)
Insomnia is a sleep disorder previously diagnosed as independent from 'secondary' influences that are attributed to psychological, physiological, or environmental factors. (2) Recently, the diagnostic criteria for insomnia disorder acknowledge co-morbid conditions and 'secondary' influences on disease progression (1) (See Table 2). Chronic insomnia is highly co-morbid with anxiety, depression and heart disease both as a precipitating factor and effect of the condition. (3) Conventional treatment includes sedative/ hypnotic drugs that cause drug tolerance, drug dependence, and adverse effects with prolonged use, and are hence often not preferred by patients. (4) Examples of pharmacological treatments include benzodiazepine and non-benzodiazepine agonists, anti-depressants and antihistamines. (5) Herbal medicine has become a popular alternative for the treatment of insomnia, (6) believed by many to be a safe and moderate approach to healing. (7)
The search strategy sought terms "insomnia" and "herbal medicine" and "clinical trials" across the following databases: Pub med, Cochrane Collaboration, CINAHL, EBSCO, Medline, Science direct, Scopus and Google Scholar. Additionally, hand searches were conducted from reference lists. The inclusion criteria consists of: insomnia disorder or primary insomnia diagnosis; transient insomnia; ingested herbs; Western herbal medicine; double-blind randomised controlled trials with a placebo group (RCTs); date range from 2003 to May 2014; population group adults.
A meta-analysis by Fernandez-San-Martin et al (2010) (8) and a systematic review by Taibi et al (2007) (9) conducted on valerian for the treatment of insomnia disorder were located. However upon detailed analysis both contained trials with methodological flaws such as poor double blinding procedures and inadequate randomisation. The trials since 2003 had better methodologies, particularly in these key areas. Furthermore, the majority of more recent trials ranked the highest score of 5 using the Jadad scale that ascertains bias and thus is a reflection of improved methodological rigour. (8) As such it was proposed that setting a date from 2003 ensured a review of 'better quality' RCTs in order to gain a clearer perspective on the efficacy of valerian as a treatment option for insomnia.
Nine research articles were identified that matched the inclusion criteria. Of these five investigated the efficacy of valerian for insomnia in adults; two investigated a combination of valerian and hops; and one each explored the usefulness of German chamomile and passionflower for this condition. The evidence for the efficacy and safety of each herb is detailed below.
Valerian (Valeriana officinalis)
Five RCTs conducted on Valeriana officinalis for the treatment of insomnia disorder in adults met the inclusion criteria (see Table 1) and, of these, no single trial reached statistical significant scoring for either subjective or objective primary outcome measures. (10,11,12,13,14) Improvements in the valerian group were noted in some trials with the majority of evidence remaining either inconclusive or unsupportive for the efficacy of valerian for sleep disorders.
The largest RCT investigating the efficacy of valerian for insomnia recruited 434 adults with primary insomnia disorder (> 5, PSQI diagnosis) that were randomised to receive either placebo or Valeriana Forte [R] (Cederroth International AB). The extract corresponded to 1200 mg V. officinalis (dried root) per tablet and the participants took 3 tablets per day for 2 weeks. (11) Primary measures did not reach statistical significance, although modest improvements favouring the valerian group for number of night awakenings and sleep duration were observed. The global self-assessment question for perceived 'better sleep' (a secondary measure) reached statistical significance (p=0.04). This RCT was relatively well conducted and included a baseline; adequate blinding procedures that masked the aroma of valerian; stratified randomisation; and stringent exclusion criteria of co-morbidities and some lifestyle factors. The second largest RCT that investigated the efficacy of valerian for insomnia was conducted over 4 weeks and recruited 270 adults that were randomised into three groups: Valerian (6.4mg valerenic acid); Kava (300mg kavalactones) and Placebo. (12) Primary objectives were to assess the efficacy of valerian for insomnia and kava for anxiety. Patients included were diagnosed with anxiety (State Trait Anxiety Inventory State) and insomnia (Insomnia Severity Index). Primary outcomes measuring changes from baseline compared with placebo showed no major differences between the groups. Three other small RCTs were found with sample sizes of between 16 and 21 participants. (10,13,14) No statistical differences between the treatment group and placebo were found.
The RCT by Taibi et al (2008) (10) examined elderly adults (n=16) diagnosed with insomnia disorder (Pittsburgh Sleep Quality Index (PSQI) who were randomised to receive either placebo or valerian (300mg/day Nature's Resource [R] valerian root extract standardised to contain 0.8% valerenic acid per 100mg soft gel capsule) for two treatment phases consisting of sleep laboratory (one night) and home (two weeks) before washout and cross over. The outcome measures included both objective and subjective sleep parameters for the sleep laboratory: Polysomnography (PSG), sleep questionnaire and home recordings (wrist autography and sleep diaries). There were no major differences between the groups, with a decrease in LT reported for both groups indicating a placebo effect. (10) Increased nocturnal wakefulness was noted in the valerian group compared to placebo, indicating a negative outcome. (10)
The small RCT by Diaper & Hindmarch (2004) (13) (n=16) examined two different doses of valerian (300mg or 600mg), from a patented extract Li 156 Sedonium [R] (Lichtwer Pharma) against placebo in a three way cross over trial for a treatment duration of one night between six-day washout periods. Objective measures included sleep cycles and psychometric function the following morning. No statistical significance was observed between dosages and placebo, although appreciably more 'drowsiness' occurred with the 600mg valerian dosage.
The small RCT by Coxeter et al (2003) (14) (n=21) conducted a series of single patient trials for adult patients diagnosed with chronic insomnia (GP diagnosis), randomised into three treatment pairs of placebo or valerian at a dosage of 2 tablets taken half an hour before bed. Each tablet contained 225mg V. officinalis root/ rhizome extract equivalent to 1g of dried root/rhizome standardised to contain 2.94 mg valerenic acids, 0.46 mg valerenal and 1.23 mg valtrates and supplied by Mediherb [R] (Warwick, Australia). The dosage was taken for one treatment week before cross-over, taking six weeks to complete. The results did not show appreciable or significant sleep parameter improvements for the patients as individuals or as a group.
Valerian has a statistically significant safety profile when comparing all groups within the trials to date. Oxman et al (2007)11 found the difference in the proportion of participants experiencing side effects in both the run-in period and treatment period for both groups to be statistically significant suggesting these effects (reduced concentration, drowsiness, tiredness, headache, dizziness, irritability and trembling) were more likely to be symptomatic of insomnia. Taibi et al (2008)10 did not find any differences in side effects listed between the groups. Coxeter et al (2003)14 reported a number of predominantly mild side effects, some moderate and a few severe, experienced by both groups such as headache, nervousness, restlessness, and some gastro-intestinal (nausea, diarrhoea) complaints. The authors postulated that some of these effects may be caused by concomitants unable to be screened out in the inclusion process. (14) Furthermore valerian does not cause dependence and does not have additive effects with alcohol. (15) This is an important factor particularly in light strong evidence associating excessive alcohol consumption with insomnia disorders. (16) According to Bos et al (2002) (17) valepotriates (a minor constituent in Valeriana officinalis) are cytotoxic, mutagenic and carcinogenic in-vitro but the relevance of this is questionable since this constituent decomposes before absorption in the human digestive tract.
Evidence of valerian-drug interactions is limited with in-vitro evidence suggesting mild to moderate inhibition of drug metabolizing enzymes, while one in-vivo study showed no significant effect on circulating levels of medications with one valerian preparation. (9) Pharmacodynamic valerian-drug interactions have proven to be beneficial in cases of benzodiazepine withdrawal, with valerian lessening the side effects of drug withdrawal. (18) This is probably due to their similar GABA-mimetic mechanisms of action. (8) Interactions with phenobarbitals, CNS depressants, sedative-hypnotics, anticonvulsants, pre-anaesthetics or adrenergic antagonists theoretically warrant caution due to the uncertainty of these interacting substances. (18) In-vivo studies have demonstrated the ability of valerian to potentiate the effects of barbiturates on sleep. (19)
Two clinical trials conducted on hops (Humulus lupulus) in combination with V. officinalis met the inclusion criteria for this review (see Table 1). (20,21) The largest RCT (n=184) compared three groups: valerian-hops (374mg/ 82mg dried extracts 5-8:1 and 7-10:1 respectively from 45% methanol solventextraction); Pharmaceutical sedative (diphenhydramine) 50mg; and Placebo. It showed marked improvements in the valerian-hops group in quality of life measures after 14 days of treatment and further improvement after the 28-day treatment duration time. (20) Subsequently a RCT with a four-week duration testing a valerian-hops combination (500mg dried valerian extract /120mg dried hops extract Ze91019) found it was significantly superior to valerian (500mg dried extract) and placebo for sleep latency (primary measure), slow-wave sleep cycles and global impression scores. (21) The valerian group failed to reach statistical significance compared to placebo, though it improved sleep latency times. (21)
Hops can be responsible for allergic skin reactions, bronchial irritations, dry cough and dyspnoea which have been observed in hops processing workers. (22) Furthermore, women processing hops experienced menstrual changes which lead to the discovery of phytoestrogens such as 8-prenylnaringenin (8-PN) and isoxanthohumol. (22) Isoxanthohumul is a pro-oestrogen since it is metabolised into 8-PN by the intestinal microflora. (23) It is difficult to measure the safety profile of hops as an ingested herb, since no RCTs have been conducted on hops singularly. A valerian-hops combination reported no serious adverse effects or cases of rebound insomnia. (20,21)
German chamomile (Chamomilla recutita syn., Matricaria chamomilla, M. recutita)
One recent RCT pilot study tested adult patients (n=34) diagnosed with chronic) primary insomnia (> 6 months--Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria), randomised to receive either placebo or German chamomile dried extract (540mg/day in a split dose of 2 x 3 tablets) for 28 days. (4) Each tablet contained 90mg of dried extract of flowering tops from solvent extraction (6:1) standardised to 2.5mg [alpha]-bisabolol and >/= 2.5mg apigenin supplied by Mediherb [R]. The outcomes were measured using a combination of subjective sleep parameters. The differences between the groups were not statistically significant but generally favoured the German chamomile group. (4) Limitations to the study include the sample size, and patients on average experiencing milder insomnia compared to other drug studies. (4) Furthermore, no previous studies were available to compare the dosage and formulation, and outcomes were limited to subjective measures. (4)
German chamomile is part of the Asteraceae family which is commonly known to cause allergies in susceptible individuals. (24) Otherwise German chamomile has a good safety profile, with a long-standing history and is generally well tolerated amongst adults. (25) Mild and transient gastrointestinal complaints were experienced by both the active and placebo groups in the recent RCT by Zick et al (2011). (4)
Passiflora incarnata (passionflower)
One recent RCT tested healthy adults (n=41) with transient insomnia, randomised to receive either passionflower herbal tea bags (2g of dried Passiflora incarnata--leaves, stems, seeds and flowers) against a placebo parsley tea bag (2g of dried Petroselinum crispum--parsley) both manufactured by Hilde Hemmes' Herbal Supplies Pty Ltd, Australia. (26) Treatment was for one week separated by one week washout period before crossing over. (26) Six subjective outcomes were measured using a sleep diary; a Spielberger's state-trait anxiety inventory (completed day seven of treatment week); and an objective PSG measure for ten of the participants (one night only). The results were statistical significant (p<0.01) for SQ compared to placebo, suggesting a benefit for adults with mild sleep disorders. Double-blinding was confirmed with no statistical difference between the groups correctly identifying the passionflower tea. There were several limitations to the study that may decrease external validity such as: ill-defined sleep disorder inclusion criteria with participants noted to have only transient sleep problems; a strict exclusion criteria applied such as extreme sleep disorders (< 4 hours/night or > 10 hours/night); history/presence of sleep disorder; >/= three naps per week; and only ten participants were involved in the PSG objective measure thereby limiting statistical power. Overall, the results warrant further research, particularly due to the external validity limitations although noting that Passiflora incarnata tea bags are an easy adjunct to a treatment plan tailored for mild sleep disorders.
Passionflower methanolic extract has a good safety profile classified by the US Food and Drug Administration as safe. (27) There have been few incidents of adverse reactions such as: a proposed 'additive' effect of Passiflora incarnata in combination with Valeriana officinalis interacting with the benzodiazepine drug (lorazepam) resulting in hand tremor, dizziness, throbbing and muscular fatigue. (27) Other idiosyncratic incidents have linked passionflower with cutaneous vasculitis and IgE mediated asthma and rhinitis. (27) Passionflower contains cyanogenic constituents which thus do not rule out toxicity though humans are regarded as having the physiological functions to detoxify cyanide adequately. (28) Furthermore, an understanding of chemical constituent concentrations for passionflower and their exact mechanisms of action remains unclear, thus indicating the need for further research on safety as well as efficacy. (27)
Overall the herbs included in this review were found to have a good safety profile but current research has failed to demonstrate the efficacy of these plants for the treatment of insomnia. Valerian is the most studied herb to date but discrepancies are apparent amongst the trials with highly variable research methodologies regarding dosage, sample size, treatment duration, preparation, and possible confounding factors due to various exclusion/ inclusion criteria. As such, further research is warranted on valerian for the treatment of insomnia disorder.
Inadequate dosage may be one of the primary problems. According to Coxeter et al (2003) (14) the dosage intervention (450mg/day) was taken from the low end of the dosage scale used by clinically experienced Australian naturopathic practitioners, and as such may have hindered the results. Despite this finding a subsequent trial by Taibi et al (2008) (10) used an even lower dosage of 300mg/day. Oxman et al (2007) (11) used a higher dosage intervention of 600mg/day where results showed a promising trend toward benefiting sleep. This highlights the advantage and possible requirement of a higher dosage of valerian for effective treatment.
A major limitation to several trials was the small sample size (n<21) limiting the statistical power of results and thus impeding internal validity. (10,13,14) Furthermore, several trials had a sub-optimal treatment duration phase of two weeks or less. Various authors have suggested that valerian has an accumulative effect after two weeks of treatment. (14,29) Further research beyond this time frame is warranted to determine efficacy after a possible accumulative effect.
The inclusion and exclusion criteria amongst the trials ranged from moderate to stringent. Coxeter et al (2003) (14) noted that the GP diagnosis of insomnia disorder may have inadequately screened patients with various co-morbidities affecting sleep and as such may account as a confounding factor. Other confounders include stimulants taken throughout the day such as caffeine, sugar containing beverages or nicotine, all known to affect cortisol levels. Several trials failed to account for these stimulants. (11,13,14) Only one trial by Taibi et al (2008) (10) accounted for these effects, although the exclusion thresholds applied are arguably high such as >/= 3 alcoholic drinks per day; >/= 6 alcoholic drinks per week and >/= 3 caffeinated drinks per day. Caffeine is an adenosine antagonist which may contribute to nullifying the proposed mechanism of action of valerian. (30) The trial by Oxman et al (2007) (11) accounted only partially for stimulants such as excluding patients with a history of alcohol and drug abuse. Alcohol consumption is known to cause rebound wakening. (29) Furthermore, the RCTs by Oxman et al (2007) (11) and Coxeter et al (2003) (14) advised participants to avoid using other preparations for insomnia and to continue self help strategies. This highlights the need for a RCT that accounts for all confounders evidenced to contribute to sleep benefit or deficit and by doing so create an even baseline for both groups.
Chemical constituents of valerian vary depending on growing conditions and variety and are very sensitive to manufacturing, processing and storage. (31) These variances may have implications for the bioequivalence of manufactured valerian preparations. Furthermore, liquid extracts of valerian to date have not been utilised in an RCT, possibly due to the obvious problem of blinding with its strong odour. (10) It would be interesting to elucidate whether a liquid extract preparation may prove more efficacious, particularly in light of the apparent instability of valerian during processing and manufacturing. (31)
Valerian has a long history of use and was described by Ellingwood (1919) (32) as a minor nerve sedative and by Felter & Lloyd (1898) (33) as a "cerebral stimulant" to relieve irritability, pain, and "wakefulness". Primary constituents of valerian include valerenic acid (and derivatives), valerenol and the valepotriates. Valerenic acid is exclusive to Valeriana officinalis whilst valepotriates are more dominant in other valerian species. The mechanism of action of valerian is thought be similar to the drug class benzodiazepines, where it interacts with the delta-amino butyric acid (GABA) neurons inthe brain. (8) In-vitro evidence suggests valerenic acid targets GABAa neuron receptors, and via their stimulation chloride channels open for neural inhibition. (34) In-vivo studies on wild mice demonstrated anxiolytic activity of valerenic acid and valerenol on the subunit P3 receptor of GABAa neurons. (35,36) Recent research by Felgentreff et al (2012) (37) suggests that whilst valerenic acid may enhance GABA neuron activity, its derivative acetoxyvalerenic acid inhibits this action on the same binding site--hence causing an opposing response. This may be a plausible reason for the idiosyncratic stimulatory effects that some people experience when taking valerian. Other proposed mechanisms of action involve the serotonergic pathways, namely the 5-[HT.sub.5a] receptor subtype implicated in the sleep-wake cycle. (15) In-vitro studies by Dietz et al (2005) (15) suggest valerenic acid is a partial agonist of the 5-HT5a receptor. Additional mechanisms of action include the adenosine receptors, where earlier in-vitro research has shown valerenic acid to agonise adenosine receptors. (30) Adenosine receptors are involved in the inhibitory central nervous system (CNS) pathways, which are typically antagonised by known stimulants such as caffeine and theophylline. (30)
Further research on the efficacy of valerian is warranted utilising a large sample sizes, higher dosage, longer duration (> three weeks) and inclusion/exclusion criteria that eliminate confounding factors such as caffeine and alcohol consumption for all participants. Due to the variable influences of sleep deficit the treatment of insomnia disorder may require a multi faceted treatment approach. (29) As such, a 'naturopathic' approach that considers diet and lifestyle habits and other factors that hinder sleep in conjunction with herbal medicine treatment may be advantageous.
Aqueous passionflower extraction (tea bags) improved SQ (p=0.01) compared to placebo for mild sleep disorders in adults despite several limitations to the trial, as investigated by Ngan & Conduit (2011). (26) This is early emerging evidence that may justify a larger well-designed trial that improves external validity by narrowing the exclusion criteria for insomnia disorders in adults. Furthermore, research that examines passionflower as a methanolic extract may prove it to be a viable treatment option. Traditionally, passionflower is described by Ellingwood (1919) (38) as useful for "wakefulness", and symptoms of anxiety such as "mental worry" and "disturbed sleep". Passionflower has a long history of use in European traditional medicine, being prescribed for various conditions including anxiety, nervousness, and insomnia. (27) The mechanism of action suggests involvement of the GABAa receptors with a proposed agonist effect by the major constituent flavonoids (hispidulin, apigenin, and quercetin) and possibly the GABA content. (27,39) In-vitro and in-vivo studies on mice confirmed anticonvulsant effects. (39)
German chamomile is a popular herb and although there is limited research investigating its efficacy, it has a 'household' reputation for enhancing sleep. Future research is warranted using a large sample size of adults diagnosed with insomnia disorder, examining efficacy with a higher dosage of German chamomile. It is an ancient medicinal herb with a long history of traditional use treating a variety of conditions including insomnia and was described by Felter (1922) (40) as a "nerve sedative". The active constituents are present in the dried flowers, and include: terpenoid volatile oils ([alpha]-bisabolol and chamazulene); phenolic flavonoid compounds (apigenin, apigenin-7-O glycoside, luteolin, patuletin, and quercetin); mucilage; and coumarins. (41) The major constituent is the flavonoid called apigenin present both as a glycoside and as a free constituent. (41) The exact mechanism of action as a sedative is unknown, but is thought to involve the interaction of the flavonoid apigenin with GABA receptors in the brain, thereby facilitating the GABA-ergic inhibitory pathway. (41)
There is a trend throughout the research to study synergistic use of valerian with other herbs for insomnia disorder. However the majority of these older trials did not meet the inclusion criteria of this review and also had methodological flaws. As such, there is scope for future research in this area. The results from the fixed valerian-hops combination Ze91019, may be the result of a particular 'synergy' or via a more broad and unknown mechanism of action of hops. (22) Historically, hops is described as having a hypnotic action to produce sleep and remove "restlessness". (42) The primary constituents are the volatile oils (terpenes) and bitter acids shown in animal studies to produce sedative effects via their involvement in GABA-ergic pathways and adenosine receptors. (22) Herbal medicine combinations may be more efficacious when combined with 'sleep hygiene' techniques and with consideration to all factors contributing to insomnia.
The aetiology and pathophysiology of insomnia disorder may differ from one individual to another due to multi-factorial causes such as genetic, environmental, behavioural and physiological factors. (43,44) As such, a 'holistic' approach that utilises herbal medicine whilst considering other contributing factors may be advantageous and more realistic in a naturopathic setting. (45)
Whole systems research (WSR) is a relatively new phenomenon, which may be a useful tool for researching the treatment of complex health conditions by a system of medicine such as naturopathy as opposed to a single agent. The current evidence in this field is limited although promising, particularly with disorders with multi factorial causes. (45,46,47) The current typical 'gold standard' RCT that attempts to align all independent variables may realistically not be the best vehicle for such research and may limit internal and external validity. (47) A WSR approach or insomnia disorder that examines holistic treatment and outcomes includes herbal medicines f may be more relevant. (45,47)
An example of a modified WSR approach was conducted by Cooley et al (2009) (48) in a RCT that examined the efficacy of Withania officinalis for the treatment of anxiety by including a 'naturopathic' baseline for placebo and intervention groups. Clearly the benefits of this clinical trial methodology would extend to disorders with multifactorial causes such as insomnia.
Based on the evidence to date, V officinalis is the most researched herb for the treatment of insomnia disorder in adults but the results do not support its use as a sole treatment. There may, however, be questions about the adequacy of the dosage and quality of valerian used in the trials reviewed. RCTs investigating the efficacy of a valerian-hops combination have shown improvement on subjective sleep measures with statistical significance proving efficacy for the fixed standardised extract Ze91019. Recent RCTs show promise for both German chamomile and passionflower in improving insomnia disorder in adults, although further research is warranted to elucidate the dosage for German chamomile, and to explore safety and efficacy of methanol extraction processes for passionflower.
Current evidence of clinical trials is lacking in the field of WSR that utilises herbal medicine in synergy with a 'naturopathic' treatment approach for insomnia disorder. Due to the myriad of factors that cause insomnia, future research in this area is necessary. A 'holistic' approach to treatment that considers a wide range of factors and advises on dietary, lifestyle, and stress management techniques as well as utilising herbal medicine may be more efficacious. Future research that addresses this gap by utilising WSR or a modified version that incorporates a standardised 'naturopathic' treatment group and placebo baseline would be advantageous. Furthermore, evidence has demonstrated the safety of valerian, hops, German chamomile and passionflower which is reassuring, particularly in light of high utilisation.
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Endeavour College of Natural Health 815 George St, Sydney NSW 2000
Table 1: Methodological features of trials that meet the inclusion criteria such as (date range from 2003; insomnia disorder; transient insomnia; Western herbal medicine; RCTs: adult population group) . Trial Sample Diagnostic size (n) Valerian RCTs 21 GP diagnosis for Coxeter et al, chronic insomnia 200314 Diaper & 16 Mild sleep Hindmarch, complaints 200413 diagnosed by sleep researcher Jacobs et al, 270 Insomnia Severity 200512 Index (ISI)--self reported sleep problems for 2 weeks--LT and sleep maintenance Oxman et al, 434 Pittsburgh sleep 200711 quality index (PSQI) score >5; insomnia > 1 month Taibi et al, 16 > 5 PSQI index 200810 Valerian-hops combination RCTs Morin et al, 184 Self-assessment 200520 occasional insomnia Koetter et al, 30 Standard 20 0721 International criteria for non-organic sleep disorder German chamomile RCT Zick et al, 34 DSM-IV criteria 20114 Passionflower RCT Ngan & 41 Sleep assessment Conduit, questionnaire 201126 Trial Duration Dosage Valerian RCTs 1 week treatment, a) dried extract 450mg/ Coxeter et al, 6 weeks total (3 day (each 225mg tablet 200314 treatment pairs of standardized to 2.94mg valerian/placebo valerenic acid, 0.46mg cross- over) valerenal, 1.23mg valtrates and equiv. 1g of dried root/ rhizome). (Mediherb [R]) b) placebo Diaper & 1 night, 6 days a) 300mg/day dried extractand Hindmarch, washout, b) 600mg/day dried extract 200413 cross-over c) placebo Jacobs et al, 28 days a) 6.4mg valerenic acid/day 200512 b) placebo Oxman et al, 14 days baseline a) 600mg/day dried extract 200711 and 14 days equivalent to 3.6g valerian treatment, 28 days b) placebo total Taibi et al, One night treatment a) 300mg (100mg each soft gel 200810 (sleep laboratory) tablet equiv. to 0.8% valerenic + 2 weeks (home), acid) washout and cross- b) placebo over, 44 days total Valerian-hops combination RCTs Morin et al, 28 days a) valerian-hops 374mg/84mg 200520 dried methanolic extracts b) Diphenhydramine 50mg c) placebo Koetter et al, 28 days a) valerian 500mg/day dried 20 0721 methanolic extract (Ze 911) b) valerian-hops 500mg/120mg dried methanolic extract (Ze 91019) c) placebo German chamomile RCT Zick et al, 28 days 540mg/day split doses 2x 3 20114 tablets of 90mg dried extract standardised 2.5mg -bisabolol and >/= 2.5mg apigenin (Mediherb [R]) Passionflower RCT Ngan & 1 week treatment, a) teabags--2g of dried Conduit, washout, cross- passionflower aerial parts 201126 over with placebo b) placebo teabags parsley Trial Species Valerian RCTs V. officinalis Coxeter et al, 200314 Diaper & V. officinalis Hindmarch, 200413 Jacobs et al, Valerenic 200512 acid constituent from V. officinalis Oxman et al, V. officinalis 200711 Taibi et al, V. officinalis 200810 Valerian-hops combination RCTs Morin et al, V. officinalis 200520 and Humulus lupulus Koetter et al, V. officinalis 20 0721 and Humulus lupulus German chamomile RCT Zick et al, Matricaria 20114 chamomilla Passionflower RCT Ngan & Passiflora Conduit, incarnata 201126 Trial Outcome measures Valerian RCTs Subjective: Coxeter et al, * ([dagger]) ([double dagger]) 200314 ([section]) ([parallel]) ([paragraph]) Diaper & Objective Hindmarch, (11pm-7am): 200413 ** Subjective: ([dagger])([dagger]) Jacobs et al, Subjective: 200512 * ([dagger]) ([double dagger] [double dagger]) Oxman et al, Subjective: 200711 ([dagger]) ([double dagger] [double dagger]) Taibi et al, Objective: ([section][section]) 200810 Subjective: * ([dagger][double dagger] [parallel][parallel]) Valerian-hops combination RCTs Morin et al, Subjective: 200520 * ([dagger][double dagger]) Objective: ([section][section]) (three separate days) Koetter et al, Subjective: 20 0721 * ([dagger] [section]) Objective: ([section][section] [paragraph][paragraph] German chamomile RCT Zick et al, Subjective: 20114 * ([dagger] [double dagger] [section] [parallel] [parallel]) (diary) Passionflower RCT Ngan & Subjective: Conduit, * ([dagger] [double dagger] 201126 [section] [parallel] [parallel]) *** Objective: ([section][section]) (only 10 participants) Sleep parameters: * Latency time (LT) ** EEG *** Fatigue to refreshed scale ([dagger]) Sleep quality (SQ) ([dagger] [dagger]) Psychometric tests next morning ([double dagger]) Sleep duration (SD) ([double dagger][double dagger]) Sleep quality measured on a visual analogue scale (SQS) ([section]) Number of night awakenings (NNA) ([section][section]) Polysomnography (PSG) ([parallel]) Refreshed next day ([parallel][parallel]) Wake after sleep onset (WASO) ([paragraph]) Energy previous day ([paragraph][paragraph]) Transporter home recorder system (QUISI) Table 2: Examples of co-morbidities and/ or secondary influences for insomnia disorder Psychological Major depressive disorder (1) Anxiety (1) Cognitive arousal (1) Physiological Pain 1 Breathing-related sleep disorder (1) Neurological or somatic diseases (2) Environmental Maladaptive sleep habits and conditioning associated with the sleep' environment 1 Noise, light, temperature (1)
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|Publication:||Australian Journal of Herbal Medicine|
|Date:||Sep 1, 2014|
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