Valerian for anxiety disorder
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To investigate the effectiveness and safety of valerian for treating any general anxiety disorder.
Background
Anxiety is a very common mental health disturbance in the general population and in the primary care setting. In the US National Comorbidity Survey Kessler 1994 found a one year prevalence for anxiety disorders of 17% and a lifetime prevalence of almost 25%. Using the Composite International Diagnostic Interview (CIDI) in 1996‐99, Bijl 1998 included 7076 people in 90 municipalities in the Netherlands and detected a prevalence rate for anxiety of 19.3% in the general population. In Brazil the prevalence of anxiety was reported at 12.1% in Brasilia, 6.9% in São Paulo and 5.4% in Porto Alegre (Almeida‐Filho 1997) . One study found a marked reduction in quality of life and psychosocial functioning in people with anxiety disorders (Mendlowicz 2000) .
Although anxiety is a treatable disease, it is often not diagnosed and treated properly. The majority of patients suffering from anxiety consult their general practitioner, and often their complaint presents as a physical symptom such as headache, palpitations, breathing difficulties or chest pain (Walley 1994). Anxiety may also be associated with physical disorders such as diabetes, arthritis and cancer. It may also be the main symptom of a specific psychiatric disorder such as generalized anxiety disorder, postraumatic stress disorder, panic or obsessive compulsive disorder.
Benzodiazepines are effective in short term treatment but their overuse may cause dependence (Priest 1988). Psychotherapy is effective and is commonly used to treat anxiety (Borkovec 1987, Borkovec 1993, Taylor 1978, Taylor 1988). A systematic review on psychotherapy for generalized anxiety disorder has been conducted and is expected to be published soon in The Cochrane Library (Kapczinski 2003). Another systematic review found that cognitive behavioral therapies and pharmacological treatments including buspirone, trazodone, imipramine and ritanserin significantly improved anxiety (Gould 1997). However psychotherapy may be an unrealistic option in public health settings in many countries as it is costly and time consuming, and although pharmacological treatments are effective, they may be limited by their side effects and cost. Herbal medicines are popularly used worlwide and could be an option if shown to be effective and secure. A systematic review on the effectiveness of Kava kava showed its superiority as compared with placebo (Pittler 2002). There is no systematic review on valerian for anxiety.
Valerian is one of the most popularly used herbal medicines for anxiety. Hydroalcoholic and aqueous extracts of valerian roots showed affinity for the GABA‐A receptor in rat brain (Mennini 1993). In another experiment valerian oil injected intraperitoneally showed central depressive and muscle relaxation activity in mice (Hendriks 1981). Valepotriates are the most active principle of valerian but are very labile and unlikely to be present in the finished preparations. In rats there is evidence of inhibition of motor activity, inhibition of aggressively, prolongation of anesthesia by exobarbital (Petkov 1974), but with better motor coordination (Von Eickstedt 1969). In humans it does not seem to potentiate the effect of alcohol but to develop a positive action in the test of concentration and efficiency (Mayer 1974), and was succesfull in the treatment of inmsonia and tension (Schmidt‐Voigt 1986, Vorbach 1996, Leathwood 1985, Donath 2000). Although valerian has been used for a long time for treating anxiety disorders its efficacy and side effects are not yet fully established.
Objectives
To investigate the effectiveness and safety of valerian for treating any general anxiety disorder.
Methods
Criteria for considering studies for this review
Types of studies
Randomised and quasi‐randomised controlled trials.
Types of participants
People with any primary diagnosis of general anxiety disorder or anxiety neurosis or chronic anxiety status, or any other disease in which anxiety is the main symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia. other types of phobia, postraumatic stress disorder), irrespective of gender and ethnic background, aged 16 and over. Studies in which anxiety is a minor symptom of a different disease (for example depression or any other psychiatric diagnoses) will be excluded.
Types of interventions
Valerian extract, any dose, regime, or method of administration. Trials will not be included when valerian is used in association with another drug.
Control: placebo, other drugs, psychotherapy, or no intervention.
Types of outcome measures
Effectiveness (measured using clinical outcome measures such as Hamilton Anxiety Scale (HAMA) and other scales for anxiety symptoms):
‐ improvement in anxiety
‐ absence of treatment response
Acceptability of treatment :
‐ number of participants reporting side effects,
‐ number of participants dropping out due to side effects.
Side effects
Other outcomes:
Total number of drop‐outs, suicide attempts, use/misuse of substances, use of health services, death and quality of life outcomes will also be considered.
Search methods for identification of studies
Electronic searches:
The Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR‐Studies) will be searched using the following terms
Intervention = Valerian
Handsearches:
The references of all identified studies will be inspected for additional studies.
Personal communication:
The first author of each included study will be contacted for information regarding unpublished trials and additional data if necessary.
The manufacturers of valerian products will be contacted for information regarding unpublished trials.
Experts in the field will be contacted for information regarding unpublished trials.
Data collection and analysis
Selection of trials
Two reviewers (LSM and BGOS) will independently select the trials found through the search strategy, and will extract the data, assess trial quality, and analyse the results. Where any disagreements occur, the third reviewer (ANA) will be consulted, and if consensus is not yet reached, data will not be included in the review until the author of the trial solves the question.
Selection of trials and data management
Reviewers will screen the abstracts of all publications which are obtained by the search strategy and are considered eligible in fulfilling the inclusion criteria. Data concerning participant characteristics, intervention details and outcome measures from the included studies will be extracted independently using a standard extraction form with the following items:
a. General information: published or not, title, authors, contact address, country, resource, publication idiom, publication year, duplication of publishing, sponsor.
b. Characteristics of the study: design, length, whether randomised and method, allocation procedure, blinding (patients, administrator care and outcome appraiser), allocation check.
c. Intervention: placebo inclusion, interventions (dose, route of administration and duration), comparisons of interventions (dose, route of administration and duration).
d. Patients: samples (randomised or convenience), exclusion criteria, total number and number in comparison groups, sex, age, basic characteristics, diagnostic criteria, length of disease and similarity of groups on basic characteristics (including any co‐morbidity), assessment on complications, sub‐groups.
e. Outcomes: those specified in the item 'types of outcomes', any other outcome assessed, other events, extension of attendance, and quality of related outcomes.
f. Results: outcomes and evaluation time (including the evaluation measure), where necessary converted to the measurement of the effects specified below; intention to treat analysis.
Quality assessment
Methodological quality of the trials included in this review will be assessed using the criteria described in the Cochrane Handbook (Clarke 2000). The Cochrane Handbook criteria are based on the evidence of a strong relationship between allocation concealment and potential for bias in the results (Schulz 1995). The categories for these criteria are as follows:
A. Low risk of bias (adequate allocation concealment)
B. Moderate risk of bias (some doubt about the results)
C. High risk of bias (inadequate allocation concealment)
For the purpose of the analysis in this review, trials will be included if they meet the criteria A or B. Additionally, a cut‐off of two points in the Jadad scale will be used to check the assessment made by the Handbook criteria (Jadad 1996). However, the Jadad scale will not used to exclude trials in this review.
Analysis
Dichotomous outcomes will be analysed by calculating relative risks (RR) for each trial with the uncertainty in each result being expressed using 95% confidence intervals (CI) and by combining individual trials in a meta‐analysis. The estimates of RR will be based on the random effects model as it takes into account any between study differences (even if there is no statistically significant heterogeneity) and gives the same result as the fixed effects model when there is no between study variance. Where overall results are significant, the number needed to treat (NNT) or number needed to harm (NNH) to produce one outcome will be calculated.
Continuous outcomes will be analysed according to their difference in the mean treatment effect and its standard deviation. When multiple outcome measures are described in a single study, for the purposes of pooling results, a single 'best available' outcome measure will be chosen for each study according to the authors' specification as the principal outcome or what is reported first. Continuous outcomes in individual studies will be combined by calculating the standardised mean difference.
Heterogeneity in the results of the trials will be assessed both by inspection of graphical presentations and by calculating a Chi‐square test of heterogeneity; it will be assumed to be present when the significance level is lower than 0.10 (p < 0.10). Where significant heterogeneity is present, an attempt will be made to explain the differences based on the clinical characteristics of the included studies. Data of these trials will not be included in the meta‐analysis. Potential sources of heterogeneity may be sample differences, diagnostic criteria or differences in medication dosage. Additionally a funnel plot will be produced to look for the possibility of publication bias. Sensitivity analyses will be performed excluding quasi‐randomised studies. Information on missing data will be clarified through contact with the authors.
