Hawthorn extract for treating chronic heart failure.

BACKGROUND: Hawthorn extract is advocated as an oral treatment option for chronic heart failure. Also, the German Commission E approved the use of extracts of hawthorn leaf with flower in patients suffering from heart failure graded stage II according to the New York Heart Association. OBJECTIVES: To assess the benefits and harms as reported in double-blind randomised clinical trials of hawthorn extract compared with placebo for treating patients with chronic heart failure. SEARCH STRATEGY: We searched CENTRAL on The Cochrane Library (issue 2, 2006), MEDLINE (1951 to June 2006), EMBASE (1974 to June 2006), CINAHL (1982 to June 2006) and AMED (1985 to June 2006). Experts and manufacturers were contacted. Language restrictions were not imposed. SELECTION CRITERIA: To be included, studies were required to state that they were randomised, double-blind, and placebo controlled, and used hawthorn leaf and flower extract monopreparations. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed the selection of studies, data extraction, and assessment of methodological quality. Data were entered into RevMan 4.2 software. Results from continuous data were reported as weighted mean difference (WMD) with 95% confidence interval (CI). Where data were suitable for combining, pooled results were calculated. MAIN RESULTS: Fourteen trials met all inclusion criteria and were included in this review. In most of the studies, hawthorn was used as an adjunct to conventional treatment. Ten trials including 855 patients with chronic heart failure (New York Heart Association classes I to III) provided data that were suitable for meta-analysis. For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo (WMD (Watt) 5.35, 95% CI 0.71 to 10.00, P < 0.02, n = 380). Exercise tolerance were significantly increased by hawthorn extract (WMD (Watt x min) 122.76, 95% CI 32.74 to 212.78, n = 98). The pressure-heart rate product, an index of cardiac oxygen consumption, also showed a beneficial decrease with hawthorn treatment (WMD (mmHg/min) -19.22, 95% CI -30.46 to -7.98, n = 264). Symptoms such as shortness of breath and fatigue improved significantly with hawthorn treatment as compared with placebo (WMD -5.47, 95% CI -8.68 to -2.26, n = 239). No data on relevant mortality and morbidity such as cardiac events were reported, apart from one trial, which reported deaths (three in active, one in control) without providing further details. Reported adverse events were infrequent, mild, and transient; they included nausea, dizziness, and cardiac and gastrointestinal complaints. AUTHORS' CONCLUSIONS: These results suggest that there is a significant benefit in symptom control and physiologic outcomes from hawthorn extract as an adjunctive treatment for chronic heart failure.

Effects of reiki in clinical practice: a systematic review of randomised clinical trials.

INTRODUCTION: The aim of this systematic review is to summarise and critically evaluate the evidence for the effectiveness of reiki. METHODS: We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. RESULTS: The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness a further RCT reported effects of reiki and distant reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care. DISCUSSION: In total, the trial data for any one condition are scarce and independent replications are not available for each condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. CONCLUSION: In conclusion, the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

Complementary therapies for back pain: is the evidence getting stronger?

Back pain is the most common reason for using complementary therapies. This analysis of the trial evidence is aimed at determining whether the evidence base for or against complementary therapies for back pain is getting stronger. Two series of systematic reviews conducted with the same methodology 5 years apart were compared. The results suggest that the weight of the evidence has increased between 2000 and 2005 for a number of interventions. The direction of the evidence, however, remained unchanged for all but one therapy. We conclude that the value of complementary therapies in the management of back pain remains encouraging but not fully convincing.

Acupuncture: its evidence-base is changing.

The effectiveness of acupuncture remains a controversial issue. The aim of this article is to evaluate trends over time in the development of the evidence-base of acupuncture. A comparison of two series of systematic reviews was conducted. The first related to the evidence-base in 2000, the second related to 2005. Both employed virtually the same methodology and criteria for evaluation. The results indicate that the evidence base has increased for 13 of the 26 conditions included in this comparison. For 7 indications it has become more positive (i.e. favoring acupuncture) and for 6 it had changed in the opposite direction. It is concluded, that acupuncture research is active. The emerging clinical evidence seems to imply that acupuncture is effective for some but not all conditions.

Horse chestnut seed extract for chronic venous insufficiency.

BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance. Therefore, oral drug treatment is an attractive option. OBJECTIVES: To review the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or reference therapy, for the treatment of CVI. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Review Group's Specialised Register (October 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005, MEDLINE (January 1966 to October 2005), EMBASE (January 1980 to October 2005), Allied and Complementary Medicine (AMED) (inception to July 2005) and Phytobase (inception to January 2001) for randomised controlled trials (RCTs) of HCSE for chronic venous insufficiency. Manufacturers of HCSE preparations and experts on the subject were contacted for published and unpublished material. There were no restrictions on language. SELECTION CRITERIA: RCTs were included if they compared oral HCSE mono-preparations with placebo, or reference therapy, in people with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded. DATA COLLECTION AND ANALYSIS: Both authors independently selected the studies and, using a standard scoring system, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm (95% confidence interval (CI) 34.9 to 49.9) measured on a 100 mm visual analogue scale. Leg volume was assessed in seven placebo-controlled trials. Meta-analysis of six trials (n = 502) suggested a WMD of 32.1ml (95% CI 13.49 to 50.72) in favour of HCSE compared with placebo. One trial indicated that HCSE may be as effective as treatment with compression stockings. Adverse events were usually mild and infrequent. AUTHORS' CONCLUSIONS: The evidence presented implies that HCSE is an efficacious and safe short-term treatment for CVI. However, several caveats exist and more rigorous RCTs are required to confirm the efficacy of this treatment option.

Adverse events of herbal food supplements for body weight reduction: systematic review.

Herbal weight-loss supplements are marketed with claims of effectiveness. Our earlier systematic review identified data from double-blind, randomized controlled trials for a number of herbal supplements. The aim of this systematic review was to assess all clinical evidence of adverse events of herbal food supplements for body weight reduction for which effectiveness data from rigorous clinical trials exist. We assessed Ephedra sinica, Garcinia cambogia, Paullinia cupana, guar gum, Plantago psyllium, Ilex paraguariensis and Pausinystalia yohimbe. Literature searches were conducted on Medline, Embase, Amed and The Cochrane Library. Data were also requested from the spontaneous reporting scheme of the World Health Organization. We hand-searched relevant medical journals and our own files. There were no restrictions regarding the language of publication. The results show that adverse events including hepatic injury and death have been reported with the use of some herbal food supplements. For herbal ephedra and ephedrine-containing food supplements an increased risk of psychiatric, autonomic or gastrointestinal adverse events and heart palpitations has been reported. In conclusion, adverse events are reported for a number of herbal food supplements, which are used for reducing body weight. Although the quality of the data does not justify definitive attribution of causality in most cases, the reported risks are sufficient to shift the risk-benefit balance against the use of most of the reviewed herbal weight-loss supplements. Exceptions are Garcinia cambogia and yerba mate, which merit further investigation.

Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials.

PURPOSE: The optimal treatment of intermittent claudication has not yet been identified. Ginkgo biloba extract has been reported to have beneficial effects. We performed a meta-analysis of the efficacy of Ginkgo biloba extract for intermittent claudication based on the results of randomized, placebo-controlled, double-blind trials. METHODS: Literature searches of MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library were performed to identify studies on the topic. Manufacturers of commercial Ginkgo biloba products and authors of original publications and reviews were contacted to provide additional information. No language restrictions were imposed. RESULTS: Eight randomized, placebo-controlled, double-blind trials were included. Meta-analysis found a significant difference in the increase in pain-free walking distance in favor of Ginkgo biloba (weighted mean difference: 34 meters, 95% confidence interval [CI]: 26 to 43 meters). In studies using similar methodological features (ergometer speed: 3 km/h, inclination: 12%) this difference was 33 meters in favor of Ginkgo biloba (95% CI: 22 to 43 meters). Adverse effects were rare, mild, and transient. CONCLUSIONS: These results suggest that Ginkgo biloba extract is superior to placebo in the symptomatic treatment of intermittent claudication. However, the size of the overall treatment effect is modest and of uncertain clinical relevance.

Guar gum for body weight reduction: meta-analysis of randomized trials.

PURPOSE: To determine the efficacy of the dietary fiber guar gum as a therapeutic option for reducing body weight by conducting a meta-analysis of randomized controlled trials. METHODS: Literature searches were performed on the electronic databases Medline, Embase, Biosis, Amed, and the Cochrane Library. Manufacturers of commercial guar gum preparations and experts on the subject were contacted to provide any published or unpublished trials. For inclusion, trials had to state that they were randomized, double blinded, and placebo controlled, used guar gum monopreparations, and reported body weight as an endpoint. No language restrictions were imposed. Two reviewers independently extracted data in a standardized manner according to predefined criteria and evaluated methodological quality using the scoring system developed by Jadad. Discrepancies were settled through discussion. RESULTS: Thirty-four trials were identified and 20 could be included. Eleven trials provided data that were suitable for statistical pooling. The meta-analysis indicated a nonsignificant difference in patients receiving guar gum compared with patients receiving placebo (weighted mean difference -0.04 kg; 95% confidence interval (CI): -2.2 to 2.1). Analysis of six trials with similar methodologic features corroborates these findings (weighted mean difference -0.3 kg; 95% CI: -4.0 to 3.5). Adverse events most frequently reported were abdominal pain, flatulence, diarrhea, and cramps. Overall, 11 patients (3%) dropped out owing to adverse events. CONCLUSIONS: This meta-analysis suggests that guar gum is not efficacious for reducing body weight. Considering the adverse events associated with its use, the risks of taking guar gum outweigh its benefits for this indication. Therefore, guar gum cannot be recommended as a treatment for lowering body weight.

Systematic review: hepatotoxic events associated with herbal medicinal products.

BACKGROUND: Large proportions of patients use herbal medicinal products, and encouraging data in terms of effectiveness exist for some of these. One aspect, however, which is still largely under-investigated is the question of potential harm. AIM: To review the recent evidence on hepatotoxic events associated with the use of herbal medicinal products. METHODS: Systematic literature searches were performed on Medline, Embase, The Cochrane Library, Amed and Ciscom. To identify additional data, searches were conducted by hand in relevant medical journals and in our own files. The screening and selection of articles and the extraction of data were performed independently by the two authors. There were no restrictions regarding the language of publication. In order to be included articles were required to report data on hepatotoxic events associated with the therapeutic use of herbal medicinal products. RESULTS: Single medicinal herbs and combination preparations are associated with hepatotoxic events. Clinically, the spectrum ranges from transient elevations of liver enzyme levels to fulminant liver failure and death. In most instances hepatotoxic herbal constituents are believed to be the cause, while others may be due to herb-drug interactions, contamination and/or adulteration. CONCLUSIONS: A number of herbal medicinal products are associated with serious hepatotoxic events. Incidence figures are largely unknown, and in most cases a causal attribution is not established. The challenge for the future is to systematically research this area, educate all parties involved, and minimize patient risk.

Location bias in controlled clinical trials of complementary/alternative therapies.

UNLABELLED: To systematically investigate location bias of controlled clinical trials in complementary/alternative medicine (CAM). METHODS: Literature searches were performed to identify systematic reviews and meta-analyses, which were used to retrieve controlled clinical trials. Trials were categorised by whether they appeared in CAM-journals or mainstream medical (MM)-journals, and by their direction of outcome, methodological quality, and sample size. RESULTS: 351 trials were analysed. A predominance of positive trials was seen in non-impact factor CAM- and MM-journals, (58) / (78) (74%) and (76) / (102) (75%) respectively, and also in low impact factor CAM- and MM-journals. In high impact factor MM-journals there were equal numbers of positive and negative trials, a distribution significantly (P < 0.05) different from all other journal categories. Quality scores were significantly lower for positive than negative trials in non-impact factor CAM-journals (P < 0.02). A similar trend was seen in low-impact factor CAM journals, but not to a level of significance (P = 0.06). There were no significant differences between quality scores of positive and negative trials published in MM-journals, except for high impact factor journals, in which positive trials had significantly lower scores than negative trials (P = 0.048). There was no difference between positive and negative trials in any category in terms of sample size. CONCLUSION: More positive than negative trials of complementary therapies are published, except in high-impact factor MM-journals. In non-impact factor CAM-journals positive studies were of poorer methodological quality than the corresponding negative studies. This was not the case in MM-journals which published on a wider range of therapies, except in those with high impact factors. Thus location of trials in terms of journal type and impact factor should be taken into account when the literature on complementary therapies is being examined.

Efficacy of homeopathic arnica: a systematic review of placebo-controlled clinical trials.

BACKGROUND: The efficacy of homeopathic remedies has remained controversial. The homeopathic remedy most frequently studied in placebo-controlled clinical trials is Arnica montana. OBJECTIVE: To systematically review the clinical efficacy of homeopathic arnica. MATERIALS AND METHODS: Computerized literature searches were performed to retrieve all placebo-controlled studies on the subject. The following databases were searched: MEDLINE, EMBASE, CISCOM, and the Cochrane Library. Data were extracted in a predefined, standardized fashion independently by both authors. There were no restrictions on the language of publications. RESULTS: Eight trials fulfilled all inclusion criteria. Most related to conditions associated with tissue trauma. Most of these studies were burdened with severe methodological flaws. On balance, they do not suggest that homeopathic arnica is more efficacious than placebo. CONCLUSION: The claim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials.

Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review.

OBJECTIVE: To assess the evidence for or against horse-chestnut seed extract (HCSE) as a symptomatic treatment of chronic venous insufficiency (CVI). DATA SOURCES: Computerized literature searches were performed in MEDLINE, EMBASE, BIOSIS, CISCOM, and the Cochrane Library (all from their respective institution to December 1996). The search terms were "horse chestnut," "Aesculus hippocastanum," "escin," and "Rosskastanie" (German for "horse chestnut"). There were no restrictions on the language of publication. STUDY SELECTION: Double-blind, randomized controlled trials of oral HCSE for patients with CVI were included. Identifiers were removed from all publications before assessment. DATA EXTRACTION: Data were extracted in a standardized, predefined manner. Trial outcomes and the methodological quality of each trial were independently assessed by the 2 reviewers. DATA SYNTHESIS: The superiority of HCSE is suggested by all placebo-controlled studies. The use of HCSE is associated with a decrease of the lower-leg volume and a reduction in leg circumference at the calf and ankle. Symptoms such as leg pain, pruritus, and a feeling of fatigue and tenseness are reduced. Five comparative trials against the reference medication indicate that HCSE and O-(beta-hydroxyethyl)-rutosides are equally effective. One trial suggests a therapeutic equivalence of HCSE and compression therapy. Adverse effects are usually mild and infrequent. CONCLUSIONS: These data imply that HCSE is superior to placebo and as effective as reference medications in alleviating the objective signs and subjective symptoms of CVI. Thus, HCSE represents a treatment option for CVI that is worth considering.

Herbal medicine.

Generalized statements about herbal medicines are nonsensical, and each remedy has to be evaluated on its own merits. Some herbal treatments can be shown to have a favorable risk-benefit profile, but for most herbal medicines the data are insufficient to determine whether they do more good than harm. The research required to fill the gaps in present knowledge should have a high priority.

Randomized, double-blind trial of chitosan for body weight reduction.

BACKGROUND: Overweight and obesity is a prevalent and costly threat to public health. Compelling evidence links overweight and obesity with serious disorders such as cardiovascular diseases and diabetes. Dietary regimen are notoriously burdened with poor compliance. Chitosan is promoted in the US and other countries as an oral remedy to reduce fat absorption and has now been incorporated as a major constituent into several over-the-counter remedies. The primary aim of this study is to investigate the clinical effectiveness of oral chitosan for body weight reduction. METHODS: Thirty-four overweight volunteers were included in a randomized placebo-controlled double-blind trial. Subjects were assigned to receive either four capsules of chitosan or indistinguishable placebo twice daily for 28 consecutive days. Measurements were taken at baseline, after 14 and 28d of treatment. Subjects maintained their normal diet and documented the type and amount of food consumed. Adverse effects were assessed and compliance monitored. RESULTS: Data from 30 subjects were entered into an intention-to-treat analysis. After four weeks of treatment, body mass index, serum cholesterol, triglycerides, vitamin A, D, E and beta-carotene were not significantly different in subjects receiving chitosan compared to those receiving placebo. Vitamin K was significantly increased after four weeks in the chitosan group compared with placebo (P<0.05). Compliance was 91.5% and 96.0% for chitosan and placebo groups respectively. CONCLUSION: The above data suggest that chitosan in the administered dosage, without dietary alterations, does not reduce body weight in overweight subjects. No serious adverse effects were reported.

Horse chestnut seed extract for chronic venous insufficiency.

BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance. Therefore, oral drug treatment is an attractive alternative. OBJECTIVES: To review the evidence from rigorous clinical trials assessing the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or other treatments for CVI. SEARCH STRATEGY: Randomised controlled trials (RCTs) of HCSE for chronic venous insufficiency were sought through EMBASE (inception to December 2001), MEDLINE and AMED (from inception to February 2004), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004), the Specialised Trials Register of the Cochrane Peripheral Vascular Diseases Group (last searched February 2004), and Phytobase (from inception to January 2001, no longer operational). Manufacturers of HCSE preparations and experts on the subject were contacted for published and unpublished material. There were no restrictions on language. SELECTION CRITERIA: RCTs were included if they compared oral HCSE mono-preparations with placebo, or other treatments, in patients with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and assessed methodological quality of the studies using a standardised scoring system, and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm [95% confidence interval (CI) 34.9 to 49.9] measured on a 100 mm visual analogue scale. Leg volume was assessed in six placebo-controlled trials. Meta-analysis of five trials (n = 289) suggested a significant reduction in favour of HCSE compared with placebo (WMD 56.3 ml [95% CI 24.1 to 88.5]). One trial indicated that HCSE may be as effective as compression stockings at reducing leg volume. Adverse events were usually mild and infrequent. REVIEWERS' CONCLUSIONS: The evidence presented implies that HCSE is an efficacious and safe short-term treatment for CVI. However, several caveats exist and more rigorous RCTs are required to assess the efficacy of this treatment option.

Feverfew for preventing migraine.

BACKGROUND: Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used for preventing attacks of migraine. OBJECTIVES: To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew versus placebo for preventing migraine. SEARCH STRATEGY: Publications describing (or which might describe) double-blind RCTs of feverfew extract for migraine were sought through the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003); PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials register of the Cochrane Pain, Palliative and Supportive care group (July 2003); and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the bibliographies of identified articles checked for further trials. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. Trials using clinical outcome measures were included. Trials focusing exclusively on physiological parameters were excluded. There were no restrictions regarding the language of publication. DATA COLLECTION AND ANALYSIS: Data on patients, interventions, methods, outcome measures, results and adverse events were extracted systematically. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Two reviewers independently selected studies, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials. REVIEWER'S CONCLUSIONS: There is insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine. It appears from the data reviewed that feverfew presents no major safety problems.

Kava extract for treating anxiety.

BACKGROUND: Synthetic anxiolytic drugs are effective for anxiety, but are often burdened with adverse events. Constraints on resources and time often render treatments such as psychological interventions impracticable. Thus, an effective and safe oral medication would be of considerable interest and a welcome addition to the therapeutic repertoire. OBJECTIVES: To systematically review the evidence from rigorous clinical trials assessing the efficacy and safety of kava extract versus placebo for the treatment of anxiety. SEARCH STRATEGY: Publications describing randomised controlled trials (RCTs) of kava extract for anxiety were sought through Medline, Embase, Biosis, AMED, CISCOM and the Cochrane Library (all from their respective inception to June 1998). The search terms used were kava, kawa, kavain, Piper methysticum and Rauschpfeffer (German common name for Piper methysticum). Manufacturers of kava preparations and experts on the subject were contacted and asked to contribute published and unpublished material. In addition, our own files were searched and the bibliographies of all of the studies identified were scanned for further trials. There were no restrictions on the language of publication. SELECTION CRITERIA: Randomized, double-blind trials of oral kava extract mono-preparations for the treatment of anxiety were included. Trials comparing kava with placebo were included. Trials assessing kava as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: All publications were blinded prior to assessment by a person not involved in the study. Data were extracted systematically. Methodological quality of all trials was evaluated using the standard scoring system developed by Jadad and colleagues. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by the two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Seven trials met the inclusion criteria. All of the reviewed trials suggest superiority of kava extract over placebo. The meta-analysis of three studies using the Hamilton Anxiety Score as a common outcome measure suggests a significant differential treatment effect in favour of kava extract (weighted mean difference: 9.7, 95% confidence interval: 3.5 - 15.8). Adverse events as reported in the reviewed trials were mild, transient and infrequent. REVIEWER'S CONCLUSIONS: The evidence presented implies that kava extract is superior compared with placebo and relatively safe as a treatment option for anxiety. These findings warrant further and more rigorous investigations into the efficacy and safety of kava extract.

Kava extract for treating anxiety.

BACKGROUND: Synthetic anxiolytic drugs are effective for anxiety, but they are burdened with adverse events. Constraints on resources and time often render treatments such as psychological interventions impracticable. Thus, an effective and safe oral medication would be of considerable interest and a welcome addition to the therapeutic repertoire. OBJECTIVES: To systematically review the evidence regarding the efficacy and safety of kava extract for the symptomatic treatment of anxiety. SEARCH STRATEGY: Computerized literature searches were performed in the databases Medline, Embase, Biosis, AMED, CISCOM and the Cochrane Library (all from their respective inception to June 1998). The search terms used were kava, kawa, kavain, Piper methysticum and Rauschpfeffer (German common name for Piper methysticum). Manufacturers of kava preparations and experts on the subject were contacted and asked to contribute published and unpublished material. In addition, our own files were searched and the bibliographies of all of the studies identified were scanned for further trials. There were no restrictions regarding the language of publication. SELECTION CRITERIA: Randomized, double-blind trials of oral kava extract mono-preparations for the treatment of anxiety were included. Trials comparing kava with placebo were included. Trials assessing kava as one of several active constituents in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: All publications were blinded prior to assessment by a person not involved in the study. Data on patients, interventions, methods, results and adverse events were extracted systematically. Methodological quality of all trials was evaluated using the scoring system developed by Jadad and colleagues. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by the two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Seven trials met the inclusion criteria. All of the reviewed trials suggest superiority of kava extract over placebo. The meta-analysis of three studies using the Hamilton Anxiety Score as a common outcome measure suggests a significant differential treatment effect in favour of kava extract (weighted mean difference: 9.69, 95% confidence interval: 3.54 - 15.83). Adverse events as reported in the reviewed trials were mild, transient and infrequent. REVIEWER'S CONCLUSIONS: These data imply that kava extract is superior to placebo and relatively safe as a symptomatic treatment for anxiety. These findings warrant further and more rigorous investigations into the efficacy and safety of kava extract.

Kava extract for treating anxiety.

BACKGROUND: Constraints on resources and time often render treatments for anxiety such as psychological interventions impracticable, while synthetic anxiolytic drugs are effective, but are often burdened with adverse events. Options which are effective and safe would be of considerable interest and a welcome addition to the therapeutic repertoire. OBJECTIVES: To assess the effectiveness and safety as reported in rigorous clinical trials of kava extract compared with placebo for treating anxiety. SEARCH STRATEGY: All publications describing (or which might describe) randomised, double-blind, placebo-controlled trials of kava extract for anxiety were sought through electronic searches on EMBASE, MEDLINE, AMED (British Library), CISCOM (Research Council for Complementary Medicine, London), Central/CCTR and CCDANCTR. The search terms that were used were kava, kawa, kavain, Piper methysticum and Rauschpfeffer (German common name for Piper methysticum). Additionally, manufacturers of kava preparations and experts on the subject were contacted and asked to contribute published and unpublished material. Hand-searches of relevant medical journals (Erfahrungsheilkunde 1996 - 2002, Forsch Komplementärmed Klass Naturheilkd 1994 - 2002, Phytomed 1994 - 2002, Alt Comp Ther 1995 - 2002), conference proceedings (e.g. FACT - Focus on Alternative and Complementary Therapies 1996 - 2002) and our own files were conducted. The searches were updated to August 2002. No restrictions regarding the language of publication were imposed. SELECTION CRITERIA: To be included studies were required to be randomised, controlled trials (RCTs), i.e. trials with a randomised generation of allocation sequences, and conducted placebo-controlled and double-blind, i.e. trials with blinding of patients and care providers. Trials using oral preparations containing kava extract as the only component (mono-preparation) were considered. Trials using single constituents of kava extract alone, assessing kava extract as one of several active components in a combination preparation or as a part of a combination therapy were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically according to patient characteristics, interventions and results. Methodological quality of all trials was evaluated using the standard scoring system developed by Jadad and colleagues. The screening of studies, selection, data extraction, validation and the assessment of methodological quality were performed independently by the two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Eleven trials with a total of 645 participants met the inclusion criteria. The meta-analysis of six studies using the total score on the Hamilton Anxiety scale as a common outcome measure suggests a significant reduction in patients receiving kava extract compared with patients receiving placebo (weighted mean difference: 5.0, 95% confidence interval: 1.1 to 8.8; p = 0.01; n = 345). Adverse events as reported in the reviewed trials were mild, transient and infrequent. REVIEWER'S CONCLUSIONS: Compared with placebo, kava extract appears to be an effective symptomatic treatment option for anxiety. 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. Further rigorous investigations, particularly into the long-term safety profile of kava are warranted.

Horse chestnut seed extract for chronic venous insufficiency.

BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance, which renders oral drug treatment an attractive option. OBJECTIVES: To review the evidence from rigorous clinical trials assessing the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or reference therapy for the treatment of CVI. SEARCH STRATEGY: Publications describing randomised controlled trials (RCTs) of HCSE for chronic venous insufficiency were sought through EMBASE, MEDLINE, Amed, and Phytobase (from inception to January 2001), The Cochrane Controlled Trials Register (Issue 1, 2001) and the Specialised Trials Register of the Cochrane Peripheral Vascular Diseases Group (April 2001). Manufacturers of HCSE preparations and experts on the subject were contacted and asked to contribute published and unpublished material. There were no restrictions on the language of publication. SELECTION CRITERIA: Randomised controlled trials of oral HCSE mono-preparations for patients with CVI were included. Trials comparing HCSE with placebo or reference medications were included. Trials assessing HCSE as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by two reviewers. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Overall, the included placebo controlled trials suggest an improvement in CVI related signs and symptoms. Leg pain was assessed in six placebo-controlled trials that reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups. One trial, which reported adequate data suggested a weighted mean difference (WMD) of 42.4 mm [95% confidence interval (CI) 34.9-49.9] measured on a 100 mm visual analogue scale. Leg volume was assessed in five placebo-controlled trials. Meta-analysis of four trials (n = 239) reporting adequate data suggested a significant reduction in favour of HCSE compared with placebo (WMD 58.6 ml [95% CI 24.9-92.2]). One trial indicated that HCSE may be as effective as treatment with compression stockings. Adverse effects are usually mild and infrequent. REVIEWER'S CONCLUSIONS: The evidence presented implies that HCSE is an efficacious and safe short-term treatment for CVI. However several caveats exist and more rigorous RCTs are required to assess the efficacy of this treatment option.