Passiflora 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 passionflower 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 commonly used to treat anxiety (Taylor 1978, Taylor 1988, Borkovec 1987, Borkovec 1993). 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 worldwide and could be an option if shown to be effective and safe. A systematic review on the effectiveness of kava kava for anxiety showed its' superiority as compared with placebo (Pittler 2002). There is no systematic review on passionflower for anxiety.
Passionflower is a folk remedy used for anxiety. In Brazil it is called "maracujá" and its' fruit is used as a popular beverage. The plant is of the passifloraceae family with about 400 species and is native to North, Central and South America. The beautiful flower that blossoms out of the unassuming bud was compared in the 15th century to the Passion of Christ, and named passion flower by the Spanish explorers who came to Peru (Olin 1989).
Most toxicity studies concern Passiflora incarnata. The plant extract contains flavonoids and alkaloids (harman or passiflorin) (Olin 1989). The herbal extract may be found in tablet forms(500mg), dried herb for oral use or by infusion. liquid extract or tincture. It has been used for many years in America and has not been associated with acute or chronic toxicity. However pharmacological profile of the extracts suggests that large doses may result in central nervous system depression and bradycardia, prolonged QTc and ventricular tachycardia (Fisher 20000. Although it has been used for a long time in treating anxiety disorders its efficacy and tolerability are not yet fully established.
Objectives
To investigate the effectiveness and safety of passionflower for treating any general anxiety disorder.
Methods
Criteria for considering studies for this review
Types of studies
:
Relevant 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
:
Intervention: Passionflower extract of any dose, regime, or method of administration. Trials will not be included when passionflower 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:
Dropout rates, 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 = Passiflora
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 passionflower 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
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 the interventions (dose, route of administration and duration).
d. Patients: samples (randomised or convenience), exclusion criteria, total number or number in comparison group, sex, age, basic characteristics, diagnostic criteria, length of disease and similarity of groups on the basic characteristics (including any co‐morbidity), assessment on complications, sub‐groups.
e. Outcomes: The ones 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 evaluative 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 be 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. When 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 mean treatment effects 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 principle outcome or what is reported first. Continuous outcomes of individual studies will be combined by caculating 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. Heterogeneity will be assumed to be present when the significance level is lower than 0.10 (p < 0.10). When 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 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.
