Effects - Internet-Based Randomized, Placebo-Controlled Trial of Kava and Valerian

[enquirewithin]

An Internet-Based Randomized, Placebo-Controlled Trial of Kava and Valerian for Anxiety and Insomnia.
Article
Medicine. 84(4):197-207, July 2005.
Jacobs, Bradly P. MD, MPH; Bent, Stephen MD; Tice, Jeffrey A. MD; Blackwell, Terri MA; Cummings, Steven R. MD, FACP
Abstract:
colon; 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.
(C) 2005 Lippincott Williams & Wilkins, Inc.



Study: Kava, Valerian Don't Work
FRIDAY, July 29 (HealthDay News)
New research is casting doubt on the effectiveness of kava and valerian root, two popular herbal remedies, with investigators finding they provided users with no more symptom relief than a placebo.
Kava, commonly used for anxiety, and valerian, used for insomnia, both worked as well as an inactive placebo when administered to 391 participants recruited via the Internet from 45 states.
According to the University of California, San Francisco team, anxiety scores decreased by 25 percent for patients taking a placebo, versus 21 percent for people taking either kava or valerian.
Effects on insomnia were about the same, with both the placebo and the herbal remedies decreasing scores by about 50 percent.
Most side effects were comparable between groups, although patients taking valerian reported a higher rate of diarrhea.
Based on the findings, the UCSF group concludes that any symptom improvement "may not be attributed to the biological effects of kava or valerian, and if attributable are no greater than the effect of placebo." They point out that the two herbal remedies are among the most popular sold today, with estimated annual U.S. sales of over $28 million.
The study is published in the July issue of Medicine.

Reputation Comments on this post:

interesting article

[ThirdEyeFloond]

Full journal article : An Internet-Based Randomized, Placebo-Controlled Trial of Kava and Valerian for Anxiety and Insomnia.

Reputation Comments on this post:

Thanks-- I couldn't access that

[enquirewithin]

This research appears to contradict other research (as is so often the case), such as this:

Valerian: a safe and effective herb for sleep problems


In an Australian study, nine healthy volunteers received single doses of either valerian root (1000mg or 500mg), the drug triazolam (0.25mg) or placebo in a double-blind, placebo-controlled, crossover trial. (1) Results confirmed that while triazolam had a detrimental effect on cognitive processes, the valerian was without effect. Another study compared even higher doses of valerian (600, 1200 and 1800mg of a 5:1 extract) with 10mg diazepam and placebo in a clinical trial of similar design. (2) Again an impairment of performance occurred for the benzodiazepine drug whereas the valerian had no impact on any parameters tested. A third study found that valerian (400mg and 800mg) was not different from placebo on any measure used of psychomotor performance or sedation. (3)
Patients aged 18 to 73 years and diagnosed with non-organic insomnia were treated in a multicentre, double-blind, randomized parallel group comparison with either 600 mg/day of valerian extract (5:1) or 10 mg/day oxazepam taken for 6 weeks. (4) A total of 202 outpatients with a mean duration of insomnia of 3.5 months at baseline were included. Sleep quality after 6 weeks showed that valerian extract was at least as efficacious as treatment with oxazepam. Both treatments markedly increased sleep quality compared with baseline (p<0.01). Adverse events occurred in 29 patients (28.4%) receiving valerian extract and 36 patients (36.0%) under oxazepam, and were all rated mild to moderate. No serious adverse reactions were reported in either group. Most patients assessed their respective treatment as very good (82.8% in the valerian group, 73.4% in the oxazepam group).
Another smaller trial of similar design compared the effect of the same dose of valerian with 10mg oxazepam over 4 weeks in 75 patients with non-organic insomnia. (5) The study showed no differences between the efficacy of valerian and oxazepam.
The efficacy and tolerability of a valerian extract preparation were investigated in an open, observational study on children aged to 6 to 12 years. (6) An average daily dosage of 2 tablets (range 1 to 4) tablets containing 300mg of 5:1 extract was administered to 130 children suffering from nervous sleep disturbances and/or nervous tension over a period of 4 weeks. Therapeutic efficacy was estimated by parents and physicians as good to very good in 95% of cases. A side effect (tiredness in the morning) was reported in only one case, which disappeared after dose adjustment.
Commentary
Unlike the benzodiazepine drugs, valerian clearly does not cause sedation or impairment of functioning in healthy volunteers. But this could be attributed to valerian having no activity on the nervous system (as detractors of phytotherapy would no doubt assert). Hence, it is pertinent that a well-designed trial found valerian to be just as effective as a benzodiazepine drug in the alleviation of non-organic insomnia. (Non-organic insomnia is characterized by a chronic, psychological impairment of the ability to initiate or maintain sleep which leads to a preoccupation with insomnia and impairment of functioning during the day.) The open trial in children also provides proof of safety here, but its efficacy should now be established in a randomized, controlled trial.
References
1. Hallam KT, Olver JS, McGrath C et al. Comparative cognitive and psychomotor effects of single doses of Valeriana officinalis and triazolam in healthy volunteers. Hum Psychopharmacol 2003; 18(8):619-625
2. Gutierrez S, Ang-Lee MK, Walker DJ et al. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 2004; 78(1):57-64
3. Glass JR, Sproule BA, Herrmann N et al. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 2003; 23(3):260-268
4. Ziegler G, Ploch M., Miettinen-Baumann A et al. Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia--a randomized, double-blind, comparative clinical study. Eur J Med Res 2002; 7(11):480-486
5. Dorn M. Wirksamkeit und vertr[per thousand]glichkeit von baldrian versus oxazepam bei nichtorganischen und nichtpsychiatrischen insomnien: Eine randomisierte, doppelblinde, klinische vergleichsstudie. Forsch Komplementarmed Klass Naturheilkd 2000; 7: 79-84.
6. Hintelmann C. Einschlafstorungen bei kindern unter 12 jahren. Z Phytother 2002; 23:60-61
by Kerry Bone, FNIMH, FNHAA

[Bajeda]

There are also some documents in the archive to consider:


A placebo-controlled study of Kava kava in generalized anxiety disorder (2002)

Int Clin Psychopharmacol. 2002 Jul;17(4):185-8

Connor KM, Davidson JR

We assessed the efficacy and safety of a botanical anxiolytic, Kava kava (Piper methysticum), in treating generalized anxiety disorder (GAD). Thirty-seven adults with DSM-IV GAD were randomly assigned to 4 weeks of double-blind treatment with kava or a matching placebo. Weekly efficacy assessments [Hamilton Anxiety Scale, Hospital Anxiety and Depression Scale (HADS), Self Assessment of Resilience and Anxiety (SARA)] and safety evaluations were conducted. Improvement was observed with both treatments but no differences were found in the principal analysis. Post-hoc analyses revealed significant differences based on baseline anxiety severity, whereby kava was superior on the SARA in low anxiety and placebo was superior on the HADS and SARA in high anxiety. Both treatments were well tolerated. Although kava was not superior to placebo, it would be premature to rule it out as efficacious in GAD.



Anxiolytic-like effects of Kava-Kava in the elevated plus maze test—a comparison with diazepam (2002)

Progress in Neuropsychopharmacology and Biological Psychiatry 2002 Jun;26(5):855-60

Rex A, Morgenstern E, Fink H.

Kava-Kava, a drug derived from a traditional psychoactive beverage used in the South Pacific, is known for tranquilizing and anxiolytic effects. Extracts made from the roots of the Kava plant (Piper methysticum G. Forster) have anxiolytic and mild sedative effects in man. To our knowledge, there are only few data concerning the efficacy of Kava-Kava in animal tests of anxiety. This study was carried out to compare the anxiolytic potential of Kava-Kava extract LI 150 with diazepam. Acute effects of diazepam and a Kava-Kava preparation, compared to their respective controls, were examined in Wistar rats using the elevated plus maze (X-maze). The time spent on open arms, the percentage of open-arm visits and parameters describing the risk assessment were evaluated. LI 150 (120-240 mg/kg p.o.) affected the behaviour measured in the X-maze test, inducing an anxiolytic like behaviour similar to diazepam (15 mg/kg p.o.). These data support the use of Kava-Kava in the treatment of anxiety.



Efficacy of Kava-Kava in the Treatment of Non-Psychotic Anxiety, Following Pretreatment with Benzodiazepines (2001)

Psychopharmacology (Berl) 2001 Sep;157(3):277-83

Malsch U, Kieser M.

A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS®1490 in non-psychotic nervous anxiety, tension and restlessness states.

The study confirms the anxiolytic efficacy and good tolerance of WS®1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment.



Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice (2003)

Psychopharmacology (Berl) 2003 Oct;170(1):33-41

Garrett KM, Basmadjian G, Khan IA, Schaneberg BT, Seale TW.

RATIONALE: Kava has been used for centuries by Pacific Islanders for its tranquilizing and sedative effects. Recent clinical trials suggest that kava has therapeutic value for the treatment of anxiety. Demonstration of kava's anxiolytic effects in animals under controlled conditions would provide additional support for its clinical potential as an anxiolytic and would facilitate investigation of its mechanism(s) of action. OBJECTIVES: This study systematically characterized the acute dosage-dependent anxiolytic and sedative effects of kava extract in well established quantitative murine behavioral assays and compared kava- and diazepam-induced behavioral changes. METHODS: Various doses of an ethanolic extract of kava root or diazepam were administered intraperitoneally to BALB/cByJ inbred mice. Behavioral changes were measured in the mirrored chamber avoidance assay and elevated plus-maze assay. Reduced latency to enter and increased time spent in a normally avoided environment operationally defined anxiolysis. Sedation was defined by a significant decrease in locomotor activity in a circular arena. RESULTS: Kava extract produced statistically significant dose-dependent anxiolytic-like behavioral changes in both assays of anxiolysis. ED(50) values for kava-induced increases in time spent inside the mirrored chamber and on the open arms of the plus maze were 125 mg/kg and 88 mg/kg, respectively. Kava extract also caused a profound decrease in locomotor activity (ED(50) of 172 mg/kg). Flumazenil, a competitive benzodiazepine receptor antagonist, blocked both the anxiolytic and sedative effects of diazepam, but had no effect on kava's behavioral actions. CONCLUSIONS: Kava extracts produce significant murine anxiolytic-like behavioral changes and sedation that are not mediated through the benzodiazepine binding site on the GABA(A) receptor complex.



Kava extract versus placebo for treating anxiety

Cochrane Review

Compared with placebo, kava extract is an effective symptomatic treatment for anxiety although, at present, the size of the effect seems small. The effect lacks robustness and is based on a relatively small sample. The data available from the reviewed studies suggest that kava is relatively safe for short-term treatment (1 to 24 weeks), although more information is required. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Also, long-term safety studies of kava are required.



Kava kava in the treatment of generalized anxiety disorder, simple phobia and specific social phobia (2001)

Phytotherapy Research 2001 Nov;15(7):646-7

Boerner, RJ

A 37-year-old female outpatient with generalized anxiety disorder, a simple phobia and a specific social phobia was treated with phytotherapy (Kava kava). Within 4 weeks, symptoms had improved by 75% and by 6 months an almost total remission of symptoms was observed. The herbal medicine was well tolerated. Kava has considerable potential value in the treatment of anxiety disorders.



Kava-kava and Anxiety: Growing Knowledge About the Efficacy and Safety

Life Sciences 2002 Apr 19;70(22):2581-97

Bilia AR, Gallon S, Vincieri FF.

Kava-kava (Piper methysticum G. Forster) has been used in social and ceremonial life in the Pacific islands from ancient times for the soporific and narcotic effects. Today several extracts standardized in the biologically active constituents kavalactones are marketed both as herbal medicinal products for anxiety disorders and as dietary supplements to improve stress disorders, nervous tension and restlessness. Unlike other substances used for these purposes, kava-kava has been shown to have minimal negative effects, and possibly positive effects, on reaction time and cognitive processing. Furthermore, it decreases anxiety without the loss of mental acuity. Although kava-kava has been found to be very effective, well tolerated, and non-addictive at therapeutic dosages, potential side effects can occur when very high doses are taken for extended periods. In addition, in the last two years unexpected high liver toxicity has been reported in two patients. Until now no studies support the liver toxicity of kavalactones and it is unknown which compound could have provoked the liver disease. On the other hand, it should be possible that unknown or unexpected constituents are the responsible or contributed to the liver toxicity.



Therapeutic Potential of Kava in the Treatment of Anxiety Disorders (2002)

CNS Drugs. 2002;16(11):731-43

Singh YN, Singh NN.

Anxiety disorders are among the most common psychiatric disorders that affect all age groups of the general population. Currently, the preferred treatment is with pharmacological drugs that have antidepressant or anti-anxiety properties. However, these agents have numerous and often serious adverse effects, including sedation, impaired cognition, ataxia, aggression, sexual dysfunction, tolerance and dependence. Withdrawal reactions on termination after long-term administration are also a major limiting factor in the use of these agents. Herbal remedies, including kava (Piper methysticum), have been shown to be effective as alternative treatments, at least in mild to moderate cases of anxiety. Kava is a social and ceremonial herb from the South Pacific. It is available in the west as an over-the-counter preparation. Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties. The pharmacological properties of kava are postulated to include blockade of voltage-gated sodium ion channels, enhanced ligand binding to gamma-aminobutyric acid (GABA) type A receptors, diminished excitatory neurotransmitter release due to calcium ion channel blockade, reduced neuronal reuptake of noradrenaline (norepinephrine), reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A(2), which antagonises GABA(A) receptor function. Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions. Until recently, the adverse effects attributed to kava use were considered mild or negligible, except for the occurrence of a skin lesion. This disorder, called kava dermopathy, occurs only with prolonged use of large amounts of kava and is reversible on reduced intake or cessation. Rare cases of interactions have occurred with pharmaceutical drugs that share one or more mechanisms of action with the kavalactones. In the past few years, about 35 cases of severe liver toxicity associated with kava intake have been reported in Europe and the US. However, a direct causal relationship with kava use has been difficult to establish in the majority of the cases, and there is insufficient evidence to implicate kava as the responsible agent. Nevertheless, until further research clarifies any causality, kava should be used with caution.



All of this research is older than the 2005 article cited in the original post. Will have to see if there is anything new on the subject.

I wonder if the "Internet-Based" aspect of the research holds any implications with regard to the results.